跳到主要內容

臺灣博碩士論文加值系統

(18.204.56.185) 您好!臺灣時間:2022/08/14 02:16
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:陳遠光
研究生(外文):Yen-Kung Chen
論文名稱:鐵離子及多巴胺形成氫氧游離基之機制
論文名稱(外文):Mechanisms of hydroxyl radical formation with iron and dopamine
指導教授:劉江川萬芳榮萬芳榮引用關係
指導教授(外文):Jiang-Chuan LiuFang-Jung Wan
學位類別:博士
校院名稱:國防醫學院
系所名稱:醫學科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2001
畢業學年度:90
語文別:中文
論文頁數:159
中文關鍵詞:鐵離子多巴胺氫氧游離基紋狀體興奮性胺基酸微透析多巴胺轉運子大白鼠
外文關鍵詞:irondopaminehydroxyl radicalstriatumexcitatory amino acidmicrodialysisdopamine transporterrat
相關次數:
  • 被引用被引用:0
  • 點閱點閱:308
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
巴金森氏症(Parkinson’s disease)是一種好發於老年人的慢性、進行性神經退化性疾病(neurodegenerative disorder)。此病的主要特徵是位在中腦黑質部緻密區(substantia nigra pars compacta)內,含有黑色素(melanin-pigmented)的多巴胺神經元(dopaminergic neurons)大量退化死亡,因而造成紋狀體(striatum)的多巴胺(dopamine)含量嚴重缺乏。目前一些研究結果顯示巴金森氏症病因仍未明,但已有很多證據顯示氧化壓力在此疾病過程扮演重要角色,例如在巴金森氏症之病人屍體發現在黑質內的鐵比正常人增加。在巴金森氏症早期由於試圖代償損失的多巴胺神經元而增加多巴胺的轉換率,導致產生過多的過氧化氫,正常生理情況下,過氧化氫會由glutathione peroxidase進一步代謝成穩定的水分子。然而,當glutathione系統受損時,則促使過氧化氫累積。 由於鐵離子可以催化多巴胺的自體氧化作用,同時經由Fenton reaction與過氧化氫作用形成高活性氫氧游離基。而麩胺酸(Glutamate)及NMDA也能增加活體內及試管外自由基的產生,因此一方面我們尋找能衰減或阻斷鐵及多巴胺氫氧游離基的形成,另一方面我們假設鐵也可能借著經由活化興奮性胺基酸(excitatory amino acid)受體,產生氫氧游離基。以大白鼠紋狀體灌流鐵(FeSO4.7H2O 200μM)或多巴胺(100μM)合併水楊酸之微透析,觀察氫氧游離基及興奮性胺基酸的產生,並給予不同的前處理藥物。結果發現apomorphine, PBN及NAC能衰減或阻斷鐵灌流大白鼠紋狀體形成氫氧游離基,而MK-801, CPP, NBQX及Mepacrine也能阻斷或衰減鐵灌流大白鼠紋狀體形成氫氧游離基,Deferoxamine可以更增加氫氧游離基的形成,卻不見原本鐵造成興奮性胺基酸增加的現象,另外以FeCl3 800μM也可以增加四到六倍氫氧游離基的形成,也不見興奮性胺基酸的增加,所以在本實驗的模式中,鐵產生的氫氧游離基大多是經由興奮性胺基酸途徑而來,少部份經由Fenton反應而來的。
在大白鼠紋狀體灌流多巴胺(100μM)形成氫氧游離基的實驗中,apomorphine及MK-801能有效的阻斷氫氧游離基的形成。 Tc-99m TRODAT-1應用在6-OHDA建立的類巴金森氏症動物模式,以autoradiography 測Tc-99m標幟TRODAT-1代表多巴胺轉運子的量和經由HPLC-ECD所得多巴胺的量,在紋狀體因6-OHDA減少的量(90%對97%)相近,然而Tc-99m TRODAT-1及autoradiography是較簡便且快速的方法。
綜合來說,在機轉上,我們提出鐵在大白鼠紋狀體也可以經由興奮性胺基酸途徑形成氫氧游離基。在處置上,apomorphine, PBN, NAC, NMDA及non-NMDA受體拮抗劑,及mepacrine皆能減緩鐵灌流大白鼠紋狀體氫氧游離基的形成;而apomorphine及MK-801也可以阻斷多巴胺在大白鼠紋狀體氫氧游離基的形成。在診斷上,Tc-99m TRODAT-1顯示紋狀體多巴胺轉運子的量與HPLC-ECD所得多巴胺的量相近,在評估動物多巴胺轉運子的功能,Tc-99m TRODAT-1是極具潛力的造影製劑。
Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder commonly observed in the elder. PD is characterized by the primary degeneration of the melanin-pigmented dopaminergic neurons of the substantia nigra pars compacta with striatal dopamine deficiency. The pathogenesis of PD remains unclear. However, evidence have shown that oxidative stress may play an important role in the pathogenic process of PD. For example, increased dopamine turnover in the early stages of PD in an attempt to compensate for dopaminergic neuronal loss may generate excessive H2O2, which would normally be inactivated by glutathione in a reaction catalyzed by glutathione peroxidase to form harmless metabolites (H2O and O2). By contrast, impaired glutathione system may lead to H2O2 accumulation. It is well-known that iron catalyze the auto-oxidation reaction of dopamine and form the highly reactive hydroxyl radical through the Fenton reaction with H2O2. In addition, elevated free radical generation has been demonstrated by glutamate and NMDA both in vitro and in vivo. In this study, we attempted to attenuate or block the generation of iron and hydroxyl radical. Also, we examined whether iron-induced excitatory amino acid (EAA) efflux with the partial hydroxyl radical formation of iron is mediated by the activation of NMDA receptor. Striatal perfusion of FeSO4.7H2O (200μM) or dopamine (100μM) with sodium salicylate microdialysis was performed in Sprague-Dawley rats and various pre-treatments were given to observe the formation of hydroxyl radical and EAA. Our results show that the formation of iron perfusion-induced hydroxyl radical in rat striatum is attenuated or blocked by apomorphine, PBN and NAC. The same phenomenon is also showed with MK-801, CPP, NBQX and Mepacrine treatments. Deferoxamine is found to increase the formation of hydroxyl radical. However, the iron-induced EAA increase is not observed. In addition, treatment of 800μM FeCl3 significantly increases the formation of hydroxyl radical up to 4- to 6-fold whereas increase of EAA is also absent. Therefore, it is concluded that, in this study, iron-induced hydroxyl radical is mainly generated through the EAA pathway whereas the rest may come from the Fenton reaction.
In the study of hydroxyl radical formation caused by dopamine (100μM) perfusion in rat striatum, it is found that apomorphine and MK-801 can effectively block the formation of hydroxyl radical. In the animal model of PD initiated by 6-OHDA, the level of Tc-99m TRODAT-1 in the striatum representing the level of dopamine transporter is close to the level of dopamine measured by HPLC-ECD (90% vs. 97%). However, measurement of Tc-99m TRODAT-1 with autoradiography is much more convenient and less time-consuming than HPLC-ECD.
To sum up, we proposed that hydroxyl radical formation in rat striatum may be generated through the EAA pathway. Apomorphine, PBN, NAC, NMDA and non-NMDA receptor antagonist, and mepacrine can all attenuate the iron-induced hydroxyl radical formation in rat striatum. Apomorphine and MK-801 may also block the dopamine-induced hydroxyl radical formation. The use of Tc-99m TRODAT-1 demonstrates that the level of striatal dopamine transporter is very close to the level of dopamine measured by HPLC-ECD. Therefore, Tc-99m TRODAT-1 appears to be an imaging agent with high potential to evaluate the function of animal dopamine transporter.
目錄
頁次
目錄………………………………………………………………………I
『圖』目錄………………………………………………………………III
中文摘要…………………………………………………………………VI
英文摘要………………………………………………………………….IX
第一章 緒言……………………………………………………………… 1
第二章 觀察鐵灌流紋狀體及黑質產生氫氧游離基及腦組織脂質過氧化情形…………………………………………………………… 9
第一節 緒言…………………………………………………………..9
第二節 材料與方法………………………………………………... 20
第三節 結果…………………………………………………………26
第四節 討論…………………………………………………………30
第三章 鐵之氧化壓力與一氧化氮的相關性………………………48
第一節 緒言…………………………………………………………48
第二節 材料與方法…………………………………………………54
第三節 結果…………………………………………………………56
第四節 討論…………………………………………………………58
第四章 鐵之氧化壓力與興奮性胺基酸之興奮性毒性的相關性……………………………………………………………66
第一節 緒言…………………………………………………………66
第二節 材料與方法…………………………………………………71
第三節 結果…………………………………………………………73
第四節 討論…………………………………………………………76
第五章 多巴胺氧化作用與氫氧游離基之形成….…………….…92
第一節 緒言…………………………………………………………92
第二節 材料與方法…………………………………………………98
第三節 結果…………………………………………………………99
第四節 討論………………………………………………………..101
第六章 巴金森氏症之動物模式及Tc-99m TRODAT-1診斷之應用…117
第一節 緒言………………………………………………………..117
第二節 材料與方法………………………………………………..123
第三節 結果………………………………………………………..126
第四節 討論………………………………………………………..128
第七章 總結………………………………………………………….…136
參考文獻………………………………………………………………...138
1. Ahagon A, Ishikawa M and Handa H: Histochemical changes of brain dopamine in an acute stage of cerebral ischemia in gerbils. Stroke 11:622-628, 1980.
2. Aizenman E, Hartnett KA and Reynolds IJ: Oxygen free radicals regulate NMDA receptor function via a redox modulatory site. Neuron 5:841-846, 1990.
3. Ames BN, Cathcart R, Schwiers E and Hochstein P: Uric acid provides an antioxidant defense in humans against oxidant- and free radical-caused aging and cancer: A hypothesis. Proc. Natl. Acad. Sci. USA 78:6858-6862, 1981.
4. Ballard PA, Tetrud JW and Langston JW: Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): Seven cases. Neurology. 35:949-956, 1985.
5. Barbeau A: Etiology of Parkinson’s disease: A research strategy. Can. J. Neurol. Sci. 11:24-28, 1984.
6. Beal MF: Mechanisms of excitotoxicity in neurologic disease. FASEB J. 6:3338-3344, 1992.
7. Beal MF: Mitochondria, free radicals, and neurodegeneration. Curr. Opin. Neurobiol. 6:661-6, 1996.
8. Beard JL, Connor and Jones BC: Iron in the brain. Nutr. Rev. 51:157-170, 1993.
9. Behl C, Davis J, Cole GM and Schubert D: Vitamine E protects nerve cells from amyloid b protein toxicity. Biochem. Biophy. Res. Commun. 186:944-950, 1992.
10. Behl C, Davis J, Lesley R and Schubert D: Hydrogen peroxide mediates amyloid b protein toxicity. Cell 77:817-827, 1994.
11. Ben-Shachar D and Youdim MBH: Intranigral iron injection induces behavioral and biochemical “parkinsonism” in rats. J. Neurochem. 57:2133-2135, 1991.
12. Ben-Shachar D, Riederer P and Youdim MBH: Iron-melanin interaction and lipid peroxidation: implications for Parkinson’s disease. J. Neurochem. 57:1609-1614, 1991.
13. Ben-Shachar D, Zuk R and Glinka Y: Dopamine neurotoxicity: inhibition of mitochondrial respiration. J. Neurochem. 64:718-723, 1995.
14. Biggs CB and Starr MS: Dopamine and glutamate control each other’s release in the basal ganglia: a microdialysis study of the entopeduncular nucleus and substantia nigra. Neurosci. Biobehavi. Rev. 21:497-504, 1997.
15. Bloem BR, Irwin I and Buruma OJS: The MPTP model: veratile contributions to the treatment of idiopathic Parkinson’s disease. J. Neuro. Sci. 97:273-293, 1990.
16. Bolanos JP, Heales SJR, Land JM and Clark JB: Effect of peroxynitrite on the mitochondrial respiratory chain: differential susceptibility of neurons and astrocytes in primary cultures. J. Neurochem. 64:1965-1972, 1995.
17. Bolanos JP, Heales SJR, Peuchen S, Barker JE, Land JM and Clark JB: Nitric oxide-mediated mitochondrial damage: a potential neuroprotective role for glutathione. Free Radic. Biol. Med. 21:995-1001, 1996.
18. Booij J, Busemann Sokole E, Stabin MG, Janssen AGM, de Bruin K and van Royen EA: Human biodistribution and dosimetry of [123I]FP-CIT: a potent radioligand for imaging of dopamine transporters. Eur. J. Nucl. Med. 25:24-30, 1998.
19. Booij J, Tissingh G, Winogrodzka A and van Royen EA: Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism. Eur. J. Nucl. Med. 26:171-182, 1999.
20. Boveris A and Chance B: The mitrochondrial generation of hydrogen peroxide: General properties and effect of hyperbaric oxygen. Biochem. J. 134:707-716, 1973.
21. Bowyer JF, Clausing P, Gough B, Slikker JW and Holson RR: Nitric oxide regulation of methamphetamine-induced dopamine release in caudate/putamen. Brain Res. 699:62-70, 1995.
22. Brannan T, Weinbreger J, Knott P, Taff I, Kaufmann H, Togasaki D, Nieves-Rosa J and Maker H: Direct evidence of acute, massive striatal dopamine release in gerbils with unilateral strokes. Stroke 18:108-110, 1987.
23. Bredt DS and Synder SH: Nitric oxide: a physiologic messenger molecule. Annu. Rev. Biochem. 63:175-195, 1994.
24. Brooks DJ: The early diagnosis of Parkinson’s disease. Ann. Neurol. 44:S10-S18, 1998.
25. Buga GM, Griscavage JM, Rogers NE and Ignarro LJ: Negative feedback regulation of endothelial cell function by nitric oxide. Circ. Res. 73:808-812, 1993.
26. Caccese D, Pratico D, Ghiselli A, Natoli S, Pignatelli P, Sanguigni V, Iuliano L and Violi F: Superoxide anion and hydroxyl radical release by collagen-induced platelet aggregation--role of arachidonic acid metabolism. Thromb. Haemostasis 83:485-490, 2000.
27. Cadet JL and Brannock C: Free radicals and the pathobiology of brain dopamine systems. Neurochem. Int. 32:117-131, 1988.
28. Cappon GD, Broening HW, Pu C, Morford L and Vorhees CV: a-Phenyl-N-tert-Butyl nitrone attenuates methamphetamine-induced depeletion of striatal dopamine without altering hyperthermia. Synapse 24:173-181, 1996.
29. Carlsson M and Carlsson A: Interactions between glutamatergic and monoaminergic systems within the basal ganglia — implications for schizophrenia and Parkinson’s disease. TINS 13:272-276, 1990.
30. Centonze D, Calabresi P, Giacomini P and Bernardi G: Neurophysiology of Parkinson’s disease: from basic research to clinical correlates. Clin. Neurophys. 110:2006-2013, 1999.
31. Chamulitrat W, Parker CE, Tomer KB and Mason RP: Phenyl N-tert-butyl nitrone forms nitric oxide as a result of its FE(III)-catalyzed hydrolysis or hydroxyl radical adduct formation. Free Radic. Res. 23:1-14, 1995.
32. Chance B, Sies H and Boveris H: Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59:527-605, 1979.
33. Cheng N, Maeda T, KumeT, Kaneko S, Kochiyama H, Akaike A, Goshima Y and Misu Y: Differential neurotoxicity induced by L-dopa and dopamine in cultured striatal neurons. Brain Res. 743:278-283, 1996.
34. Chiueh CC, Murphy DL, Miyake H, Lang K, Tulsi P and Huang SJ: Hydroxyl free radical formation reflected by salicylate hydroxylation and neuromelanin: in vivo markers for oxidation injury of nigral neurons. Ann. N.Y. Acad. Sci. 679:370-375, 1993.
35. Choi DW: Ionic dependence of glutamate neurotoxicity. J. Neurosci. 7:369-379, 1987.
36. Church WH and Fong YT: Changes in uric acid during acute infusion of MPP+, 6-OHDA, and FeCl3. A microdialysis study in the substantia nigra of the guinea pig. Mol. & Chem. Neuropathol. 27:131-144, 1996.
37. Ciliax BJ, Heilman C, Demchyshyn LL, Pristupa ZB, Ince E, Hersch SM, Niznik HB and Levey AI: The dopamine transporter: immunochemical characterization and localization in brain. J. Neurosci. 15:1714-1723, 1995.
38. Cleeter MWJ, Cooper JM and Shapira AHV: Irreversible inhibition of mitochondrial complex I by 1-methyl-4-phenylpyridinium: evidence for free radical involvement. J. Neurochem. 58:786-789, 1992.
39. Clemens JA and Phebus LA: Dopamine depletion protects striatal neurons from ischemia-induced cell death. Life Sci. 42:707-713, 1988.
40. Cocks TM, Angus JA, Campbell JH and Campbell GR: Release and properties of endothelium-derived relaxing factor (EDRF) from endothelial cells in culture. J. Cell Physiol. 123:310-320, 1985.
41. Cohen A: Current status of iron chelation therapy with desferrioxamine. Semin. Hematol. 27:86-90, 1990.
42. Cohen G: Oxy-radical toxicity in catecholamine neurons. Neurotoxicology 5:77-82, 1984.
43. Cooper JR, Bloom FE and Roth RH: Amino Acid Transmitters. in: The Biochemical Basis of Neuropharmacology. edited by Cooper JR, Bloom FE and Roth RH, 7th ed., New York, Oxford University Press, 1996, pp. 126-193.
44. Coyle JT and Puttfarcken P: Oxidative stress, glutamate, and neurodegenerative disorders. Science. 262:689-695, 1993.
45. Crowder JM and Bradford HF: Inhibitory effects of noradrenaline and dopamine on calcium influx and neurotransmitter glutamate release in mammalian brain slices. Eur. J. Pharmacol. 143:343-352, 1987.
46. Culcasi M, Lafon-Cazal M, Pietri S and Bockaert J: Glutamate receptors induce a burst of superoxide via activation of nitric oxide synthase in arginine-depleted neurons. J. Biol. Chem. 269:12589-12593, 1993.
47. Dawson TM, Dawson VL and Snyder SH: A novel neuronal messenger molecule in brain: the free radical, nitric oxide. Ann. Neurol. 32:297-311, 1992.
48. Defrance JF, Sikes RW and Chronister RB: Dopamine action in the nucleus accumbens. J. Neurophysiol. 54:1568-1577, 1985.
49. Dexter DT, Sian J, Jenner P and Marsden CD: Implications of alterations in trace element levels in brain in Parkinson''s disease and other neurological disorders affecting the basal ganglia. Ad. Neurol. 60:273-81, 1993.
50. Donaldson J: The pathophysiology of tracer metal: neurotransmitter interaction in the CNS. TIPS 75-78, 1981.
51. Drapier JC and Hibbs JBJr: Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells. J. Immunol. 40:2829-2838, 1988.
52. Duarte CB, Santos PF, Sanchez-Prieto J and Carvalho AP: Glutamate release evoked by glutamate receptor agonists in cultured chick retina cells: modulation by arachidonic acid. J. Neurosci. Res. 44:363-373, 1996.
53. Dubey A, Forster MJ and Sohal RS: Effect of the spin-trapping compound N-tetra-butyl-a-phenylnitrone on protein oxidation and life span. Arch. Biochem. Biophys. 324:249-254, 1995.
54. Dumuis A, Sebben, Haynes L, Pin JP and Bockaert J: NMDA receptors activate the arachidonic acid cascade system in striatal neurons. Nature 336:68-70, 1988.
55. Ellison G, Eiso MS, Huberman HS and Daniel F: Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration. Science 201:276-278, 1978.
56. Fenton HJH: Oxidation of tartaric acid in presence of iron. J. Chem. Soc. 65:899-909, 1894.
57. Ferrari G, Yan CYI and Greene LA: N-acetylcysteine (D- and L-Stereoisomers) prevents apoptotic death of neuronal cells. J. Neurosci. 15:2857-2866, 1995.
58. Ferrendelli JA, Chang MM and Kinscherf DA: Elevation of cyclic GMP levels in central nervous system by excitatory and inhibitory amino acids. J. Neurochem. 22: 535-540, 1974.
59. Filloux F and Townsend JJ: Pre- and postsynaptic neurotoxic effects of dopamine demonstrated by intrastriatal injection. Exp. Neurol. 119:79-88, 1993.
60. Fontecave M and Pierre JL: Iron: Metabolism, toxicity and therapy. Biochimie 75:767-773, 1993.
61. Fornstedt B, Bergh I, Rosengren E and Carlsson A: An improved HPLC-electrochemical detection method for measuring brain levels of 5-S-cysteinyldopamine, 5-S-cysteinyl-3,4-dihydroxyphenylalanine, and 5-S-cysteinyl-3,4-dihydroxyphenylacetic acid. J. Neurochem. 54:578-586, 1990.
62. Forsman M, Fleischer JE, Milde JH, Steen PA and Michenfelder JD: Superoxide dismutase and catalase failed to improve neurologic outcome after complete cerebral ischemia in the dog. Acta. Anaesthesiol. Scand. 32:152-155, 1988.
63. Frankel JP, Lees AJ, Kempster PA and Stem GM: Subcutaneous apomorphine in the treatment of Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry. 53:96-101, 1990.
64. Freed C, Revay R, Vaughan RA, Kriek E, Grant S, Uhl GR and Kuhar MJ: Dopamine transporter immunoreactivity in rat brain. J. Comp. Neurol. 359(2):340-349, 1995.
65. Frei K, Siepl C, Groscurth P, Bodmer S, Swerdel C and Fontana A: Antigen presentation and tumor cytotoxicity to interferon-treated microglia cells. Eur. J. Immunol. 17:1271-1278, 1987.
66. Fridovich I: Superoxide radical: an endogenous toxicant. Ann. Rev. Pharmacol. 23:239-257, 1983.
67. Fridovich I: Biological effects of superoxide radical. Arch. Biochem. Biophys. 247:1-11, 1986.
68. Frost JJ, Rosier AJ, Reich SG, Smith JS, Ehlers MD, Synder SH, Ravert HT and Dannals RF: Positron emission tomography imaging of the dopamine transporter with 11C-WIN 35,428 reveals marked declines in mild Parkinson’s disease. Ann. Neurol. 34:423-431, 1993.
69. Fuller RW and Hemrick-Luecke SK: Long-lasting depletion of striatal dopamine by a single injection of amphetamine in iprindole-treated rats. Science 209:305, 1980.
70. Furchgott RF: Studies on relaxation of rabbit aorta by sodium nitrite: the basis for the proposal that the acid-activatable inhibitory factor from retractor penis is inorganic nitrite and the endothelium-derived relaxing factor is nitric oxide. in: Vasodilatation: Vascular Smooth Muscle, Peptides, Autonomic Nerves and Endothelium, edited By Vanhoutte PM and Raven Press, New York, 1988, pp. 401-414.
71. Furchgott RF and Zawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. (Lond.) 288:373-376, 1980.
72. Gabrielsson B, Robson T, Norris D and Chung SH: Effects of divalent metal ions on the uptake of glutamate and GABA from synaptosomal fractions. Brain Res. 384:218-223, 1986.
73. Gancher ST, Nutt JG and Woodward WR: Apomorphine infusional therapy in Parkinson’s disease: clinical utility and lack of tolerance. Mov. Disord. 10:37-42, 1995.
74. Gardiner IM, Li A, Patel N, Ball S and de Belleroche J: Excitotoxin induction of ornithine decarboxylase in cerebral cortex in reduced by phospholipase A2 inhibition. Life Sci. 51:77-81, 1992.
75. Garthwaite J, Charles SL and Chess-Williams R: Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 336:385-388, 1988.
76. Garthwaite J: Glutamate, nitric oxide and cell-cell signaling in the nervous system. TINS. 14:60-67, 1991.
77. Gassen M, Glinka Y, Pinchasi B and Youndim MBH: Apomorphine is a highly potent free radical scavenger in rat brain mitochondrial fraction. Eur. J. Pharmacol. 308:219-226, 1996.
78. Gerlach M, Ben-Sachar D, Riederer P and Youdim MBH: Altered brain metabolism of iron as a cause of neurodegenerative diseases? J. Neurochem. 63:793-807, 1994.
79. Gerlach M and Riederer P: Animal models of Parkinson’s disease: an empirical comparison with the phenomenology of the disease in man. J. Nerual Transm. 103:987-1041, 1996.
80. Germain D, Manaye K, Smith WK, Woodward DJ and Saper CB: Midbrain dopaminergic cell loss in Parkinson’s disease: computer visualization. Ann. Neurol. 26:507-514, 1989.
81. Gerschman R: Oxygen poisoning and X-irradiation: A mechanism in common. Science 199:623-626, 1954.
82. Gilman SC, Bonner MJ and Pellmar TC: Peroxide effects on [3H]L-glutamate release by synaptosomes isolated from the cerebral cortex. Neurosci Lett 140:157-160, 1992.
83. Gilman SC, Bonner MJ and Pellmar TC: Effect of oxidative stress on excitatory amino acid release by cerebral cortical synaptosomes. Free Rad. Biol. Med. 15:671-675, 1993.
84. Gohima Y, Ohno K, Nakamura S, Miyamae T, Misu Y and Akaike A: DOPA induces Ca2+-dependent and tetrodotoxin-sensitive release of endogenous glutamate from rat striatal slices. Brain Res. 617:167-170, 1993.
85. Graham DG, Tiffany SM, Bell WR and Gutknecht WF: Autoxidation versus covalent binding quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine and related compounds towards C1300 neuroblastoma cells in vitro. Mol. Pharmacol. 14:644-653, 1978.
86. Graham DG: On the origin and significance of neuromelanin. Arch. Patho. Lab. Med. 103:359-362, 1979.
87. Griscavage JM, Fukuto JM, Komori Y and Ignarro LJ: Nitric oxide inhibits neuronal nitric oxide synthase by interacting with the heme prosthetic group. Role of tetrahydrobiopterin in modulating the inhibitory action of nitric oxide. J. Biol. Chem. 269:21644-21649, 1994.
88. Gross SS and Wolin MS: Nitric oxide: pathophysiological mechanisms. Annu. Rev. Physiol. 57:737-769, 1995.
89. Group PS: Effect of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N. Engl. J. Med. 328:76-83, 1993.
90. Grunblatt E, Mandel S, Gassen M and Youdim MB: Potent neuroprotective and antioxidant activity of apomorphine in MPTP and 6-hydroxydopamine induced neurotoxicity. J. Neural. Transm. Suppl. 55:57-70, 1999.
91. Gutteridge JMC and Halliwell B: The measurement and mechanism of lipid peroxidation in biological systems. Trend in Bio. Sci. 15:129-135, 1990.
92. Haber F and Weiss J: The catalytic decomposition of hydrogen peroxide by iron salts. Proc. R. Soc. London. 147:322-351, 1934.
93. Hall S, Rutledge JN and Schallert T: MRI, brain iron and experimental Parkinson''s disease. J. Neuro.Sci. 113:198-208,1992.
94. Hallgren B and Sourander P: The effect of age on the nonhaemin iron in the human brain. J. Neurochem. 3:41-51, 1958.
95. Halliwell B: Oxidants and central nervous system: Some fundamental questions. Acta Neurol. Scand. 126:23-33, 1989.
96. Halliwell B: Reactive oxygen species and the central nervous system. J. Neurochem. 59:1609-1623, 1992.
97. Halliwell B and Gutteridge JMC: Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J. 219:1-14, 1984.
98. Halliwell B and Gutteride JMC: Role of free radicals and catalytic metal ions in human diaease: an overview. Methods Enzymol. 186:1-85, 1990.
99. Halliwell B and Gutteridge JMC: Free radicals in biology and medicine, 3rd ed. Clarendon Press, Oxford, UK, 1999.
100. Hammer B, Parker Jr WD and Bennett Jr JP: NMDA receptors increase OH radicals in vivo by using nitric oxide synthase and protein kinase C. Neuroreport 5:72-74, 1993.
101. Hartley A, Cooper JM, Schapira AHV: Iron induced oxidative stress and mitochondrial dysfunction: relevance to Parkinson’s disease. Brain Res. 627:349-353, 1993.
102. Hastings TG, Lewis DA and Zigmond MJ: Role of oxidation in neurotoxic effects of intrastriatal dopamine injections. Proc. Natl. Acad. Sci. USA, 1996.
103. Hughes AJ, Daniel SE, Kilford and Lees AJ: The accuracy of the clinical diagnosis of Parkinson’s disease: a clinicopathological study of 100 cases. J Neurol. Neurosurg. Psychiatry. 55:181-184, 1992.
104. Ilgin N, Zubieta J, Reich SG, Dannals RF, Ravert HT and Frost JJ: PET imaging of the dopamine transporter in progressive supranuclear palsy and Parkinson''s disease. Neurology. 52:1221-1226, 1999.
105. Imperato A, Tanda G, Frau R and Di Chiara G: Pharmacological profile of dopamine receptor agonists as studied by brain dialysis in behaving rats. J. Pharmacol. Exp. Ther. 245:257-264, 1988.
106. Iversen LL: Role of transmitter uptake mechanisms in synaptic neurotransmission. Br. J. Pharmacol. 41:571-591, 1971.
107. Jaber M, Jones S, Giros B and Caron MG: The dopamine transporter: a crucial component regulating dopamine transmission. Mov. Disord. 12:629-633, 1997.
108. Jellinger K, Paulus W, Grundke-Iqbal I, Riederer P and Youdim MBH: Brain iron and ferritin in Parkinson’s and Alzheimer’s diseases. J. Neural Transm. Park. Dis. Dement. Sect. 2:327-340, 1990.
109. Jenner P: Oxidative damage in neurodegenerative disease. Lancet 34:796-798, 1994.
110. Jenner P, Rupniak NMJ, Rose S, Kelly E, Kilpatrick G, Lees A and Marsden CD: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-incuced parkinsonism in the common marmoset. Neurosci. Let. 50:85-90, 1984.
111. Jenner P: Oxidative damage in neurodegenerative disease. Lancet 34:796-798, 1994.
112. Jenner P and Olanow WC: Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 47:S161-S170, 1996.
113. Jonsson G: Chemical neurotoxins as denervation tools in neurobiology. Ann. R. Neurosci. 3:169-187, 1980.
114. Keller JN, Germeyer A, Begley JG and Mattson MP: 17β-Estradiol attenuates oxidative impairment of synaptic Na+/K+-ATPase activity, glucose transport, and glutamate transport induced by amyloid β-peptide and iron. J. Neurosci. Res. 50:522-530, 1997.
115. Knuckey NW, Palm D, Primiano M, Epstein MH and Johanson CE: N-acetylcysteine enhances hippocampal neuronal survival after transient forebrain ischemia in rats. Stroke 26:305-311, 1995.
116. Krebs MO, Desce JM, Kermel ML, Gaucy C, Godeheu G Cheramy A and Glowinski J: Glutamatergic control of dopamine release in the rat striatum: Evidence for presynaptic N-methyl-D-aspartate receptors on dopaminergic nerve terminals. J. Neurochem. 56:81-85, 1991.
117. Kung HF, Kim HJ, Kung MP, Meegalla SK, Plossl K and Lee HK: Imaging of dopamine transporters in humans with technetium-99m TRODAT-1.Eur. J. Nucl. Med. 23:1527-1530, 1996.
118. Kung MP, Stevenson DA, Plossl K, Meegalla SK, Beckwith A, Essman WD, Mu M, Lucki I and Kung HF: [99mTc]TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent. Eur. J. Nucl. Med. 24:372-380, 1997.
119. Kushner SA, McElgin WT, Kung MP, Mozley PD, Plossl K, Meegalla SK, Mu M, Dresel S, Vessotskie JM, Lexow N and Kung HF: Kinetic modeling of [99mTc]TRODAT-1: a dopamine transporter imaging agent. J. Nucl. Med. 40:150-158, 1999.
120. Lafon-Cazal M, Pietri S, Culcasi M and Bockaert J: NMDA-dependent superoxide production and neurotoxicity. Nature 364:535-537, 1993.
121. Lai CT and Yu PH: Dopamine- and L-b-3,4-dihydroxyphenylalanine hydrochlorid (L-Dopa)-induced cytotoxicity towards catecholaminergic neuroblastoma SH-SY5Y cells. Biochem. Pharm. 53:363-372, 1997.
122. Lancelot E, Callebert J, Plotkine M and Boulu RG: Striatal dopamine participates in glutamate-induced hydroxyl radical generation. Neuroreport 6: 1033-1036, 1995.
123. Lancelot E, Revaud ML, Boulu RG, Plotkine M and Callabert J: A microdialysis study investigating the mechanisms of hydroxyl radical formation in rat striatum exposed to glutamate. Brain Res. 809:294-296, 1998.
124. Lange KW, Loschmann P-A and Sofic E: The competitive NMDA antagonist CPP protect substantia nigra neurons from MPTP-induced degeneration in primate. Naunyn. Schmiedebergs. Arch. Pharmacol. 348:586-592, 1993.
125. Lauterburg BH, Corcoran GB and Mitchell JR: Mechanism of action of N-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. J. Clin. Invest. 71: 980-991, 1983.
126. Lawrence AJ and Jarrott B: Nitric oxide increases interstitial excitatory amino acid release in the rat dorsomedial medulla oblongata. Neurosci. Lett. 151:126-129, 1992.
127. Lazarewicz JW, Wroblewski JT and Costa E: N-Methyl-D-Aspartate-Sensitive glutamate receptors induce calcium-mediated arachidonic acid release in primary cultures of cerebellar granule cells. J. Neurochem. 55:1875-1881, 1990.
128. Lees AJ: Dopamine agonists in Parkinson’s disease: a look at apomorphine. Fund. Clin. Pharmacol. 7:121-128, 1993.
129. Lin HC, Wan FJ and Tseng CJ: Modulation of cardiovascular effects produced by nitric oxide and ionotropic glutamate receptor interaction in the nucleus tractus solitarii of rats. Neuropharmacology 38:935-941, 1999.
130. Lipton SA, Choi YB, Pan ZH, Lei SZ, Vincent Chen HS, Sucher NJ. Loscalzo J, Singel DJ and Stamler JS: A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364: 626-632, 1993.
131. Liu D: Generation and detection of hydroxyl radical in vivo in rat spinal cord by microdialysis administration of Fenton''s reagents and microdialysis sampling. J. Biochem. & Biophys. Methods. 27:281-291, 1993.
132. Liu D, Yang R, Yan X and McAdoo DJ: Hydroxyl radicals generated in vivo kill neurons in the rat spinal cord: electrophysiological, histological, and neurochemical results. J. Neurochem. 62:37-44, 1994.
133. Lodge M. and Johnson KM: Noncompetitive excitatory amino acid receptor antagonists. Trends Pharmacol. Sci. 11:80-86, 1990.
134. Lovell MA, Ehmann WD, Butler SM and Markesbery WR: Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer’s disease. Neurology 45:1594-1601, 1995.
135. Madras BK, Meltzer PC, Liang AY, Elmaleh DR, Babich J and Fischman AJ: Altropane, a SPECT or PET imaging probe for dopamine neurons: I. Dopamine transporter binding in primate brain. Synapse 29:93-104, 1998.
136. Martin WRW, Ye FQ and Allen PS: Increasing striatal iron content associated with normal aging. Mov. Disord. 13:281-286, 1998.
137. Matarredona ER, Santiago M, Cano J and Machado A: Involvement of iron in MPP+ toxicity in substantia nigra: protection by desferrioxamine. Brain Res. 733:76-81, 1997.
138. Matsui T, Johsita H, Asano T and Tanaka J: Effect of a free radical scavenger, ebselen, on cerebral ischemia. In: Krieglstein J, Oberpichler H, eds. Pharmacology of Cerebral Ischemia. Stuttgart, Germany: Wissenschaftiliche Verlagsgesellschaft, Publishers, 1990, pp. 363-367.
139. Mattson MP, Lovell MA, Furukawa K and Markesbery WR: Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of [Ca2+]i and neurotoxicity, and increase antioxidant enzyme activities in hippocampal neurons. J. Neurochem. 65:1740-1751, 1995.
140. McBain CJ and Mayer ML: N-methyl-D-aspartic acid receptor structure and function. Physiol. Rev. 74:723-60, 1994.
141. McCall T and Vallance P: Nitric oxide takes center stage with newly defined roles. Trends Pharmacol. Sci. 13:1-6, 1991.
142. McDonald JW, Silverstein FS and Johnston MV: Neuroprotective effects of MK-801, TCP, PCP and CPP against N-methyl-D-aspartate induced neurotoxicity in an in vivo perinatal rat model. Brain Res. 490:33-40, 1989.
143. McLaughlin BA, Nelson D, Erecinska M and Chesselet MF: Toxicity of dopamine to striatal neurons in vitro and potentiation of cell death by a mitochondrial inhibitor. J. Neurochem. 70:2406-2415, 1998.
144. McNaught KStP and Brown GC: Nitric oxide causes glutamate release from brain synaptosomes. J. Neurochem. 70:1541-1546, 1998.
145. Mecocci P, MacGarvey U, Kaufman AE, Koontz D, Shoffner JM, Wallace DC and Beal MF: Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease. Annals Neurol. 36:747-751, 1994.
146. Meldrum BS and Garthwaite J: Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol. Sci. 11:379-387, 1990.
147. Meltzer PC and Madras BK: Imaging of dopamine transporters in humans with technetium-99m TRODAT-1. Eur. J. Nucl. Med. 24:462-463, 1997.
148. Michel PP and Hefti F: Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neuron in culture. J. Neurosci. Res. 26: 428-435, 1990.
149. Miller RJ, Murphy SN and Glaum SR: Neuronal Ca2+ Channels and their regulation by excitatory amino acids. Ann. N.Y. Acad. Sci. 568:149-158, 1989.
150. Mizusawa A, Ogawa H, Kikuchi Y, Hida W, Kurosawa H, Okabe S, Takishima TT and Shirato K: In Vivo release of glutamate in nucleus tractus solitarii of the rat during hypoxia. J. Physiol. 478:55-65, 1994.
151. Mohanakumar KP, Hanbauer I and Chiueh CC: Neuroprotection by nitric oxide against hydroxyl radical-induced nigral neurotoxicity. J. Chem. Neuroanat. 14:195-205, 1998.
152. Mohanakumar KP, de Bartolomeis A, Wu RM, Yeh KJ, Sternberger L, Peng SY, Murphy DL and Chiueh CC: Ferrous-citrate complex and nigral degeneration: evidence for free radical formation and lipid peroxidation. Ann. N. Y. Acad. Sci. 738:392-400, 1994.
153. Monaghan DT, Bridges RJ and Cotman CW: The excitatory amino acid receptors: their classes, pharmacology and distinct properties in the function of the central nervous system. Ann. Rev. Pharmacol. Toxicol. 29:365-402, 1989.
154. Moncada S and Palmer RMJ: The L-arginine: nitric oxide pathway in the vessel wall. In: Nitric Oxide from L-arginine: A Bioregulatory System. edited by Moncads S and Higgs EA, Elsevier, Amsterdam, 1990, pp 19-33.
155. Moncada S, Radomski MW and Palmer RMJ: Nitric oxide. Biochem. Pharmacol. 37:2495-2501, 1988.
156. Moncada S, Palmer RMJ and Higgs EA: Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol. Rev. 43:109-142, 1991.
157. Monteiro HP and Winterbourn CC: 6-Hydroxydopamine releases iron from ferritin and promotes ferritin-dependent lipid peroxidation. Biochem. Pharm. 38: 4177-4182, 1989.
158. Mozley PD, Stubbs JB, Plossl K, Dresel SH, Barraclough ED, Alavi A, Araujo LI and Kung HF: Biodistribution and dosimetry of TRODAT-1: a technetium-99m tropane for imaging dopamine transporters. J. Nucl. Med. 39:2069-2076, 1998.
159. Nakaki T, Nakayama M and Kato R: Inhibition by nitric oxide and nitric oxide-producing vasodilators of DNA synthesis in vascular smooth muscle cells. Eur. J. Pharmacol. 189:347-353, 1990.
160. Nappi AJ and Vass E: Hydroxyl radical formation resulting from the interaction of nitric oxide and hydrogen peroxide. Biochim. Biophys. Acta 1380:55-63, 1998.
161. Nathan CF and Hibbs JB: Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr. Opin. Immunol. 3:65-70, 1991.
162. Nirenberg MJ, Vaughan RA, Uhl GR, Kuhar MJ and Pickel VM: The dopamine transporter is localized to dendritic and axonal plasma membranes of nigrostriatal dopaminergic neurons. J Neurosci. 16:436-447, 1996.
163. Nirenberg MJ, Chan J, Pohorille A, Vaughan RA, Uhl GR, Kuhar MJ and Pickel VM: The dopamine transporter: comparative ultrastructure of dopaminergic axons in limbic and motor compartments of the nucleus accumbens. J. Neurosci. 17:6899-6907, 1997.
164. Noguchi T and Nakano M: Effect of ferrous ions on microsomal phospholipid peroxidation and related light emission. Biochem. Biophys. Acta 386:446-455, 1974.
165. Nohl H and Jordan W: the mitrochondrial site of superoxide formation. Biochem. Biophys. Res. Commun. 138:533-539, 1986.
166. Nowycky MC and Roth RH: Dopaminergic neurons: role of presynaptic receptors in the regulation of transmitter biosynthesis. Prog. Neuropsychopharmacol. 2:139-158, 1978.
167. Novelli A, Reilly JA, Lysko PG and Henneberry RC: Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res. 451:205-212, 1988.
168. Nunez MT, Gaete V, Watkins JA and Glass J: Mobilization of iron from endocytic vesicles. J. Biol. Chem. 265:6688-6692, 1990.
169. Obata T, Hosokawa H and Yamanaka Y: Effect of ferrous iron on the generation of hydroxyl free radicals by liver microdialysis perfusion of salicylate. Compara. Biochem. & Physiol. - C: Compara. Pharmacol. & Toxicol. 106:629-634, 1993.
170. Obata T and Yamanaka Y: Effect of iron (II) on the generation of hydroxyl free radicals in rat myocardium. Biochem Pharmacol. 51:1411-1413, 1996.
171. Obata T and Yamanaka Y: Effect of .OH scavenging action by non-SH-containing angiotensin converting enzyme inhibitor imidaprilat using microdialysis. J. Physiol. Paris. 92:1-4, 1998.
172. Octave JN, Schneider YJ, Trouet A and Crichton RR: Iron uptake and utilization by mammalian cells. 1. Cellular uptake of transferrin and iron. Trends Biochem. Sci. 8:217-220, 1983.
173. O’Dell SJ, Weihmuller FB and Marshall JF: Multiple methamphetamine injections induce marked increases in extracellular striatal dopamine which correlate with subsequent neurotoxicity. Brain Res. 564:256-260, 1991.
174. O’Dell SJ, Weihmuller FB and Marshall JF: Methamphetamine-induced dopamine overflow and injury to striatal dopamine terminals: Attenuation by dopamine D1 or D2 antagonists. J. Neurochem. 60:1792-1799, 1993.
175. Offen D, Ziv I, Barzilai A, Gorodin S, Glater E, Hochman A and Melamed E: Dopamine-melanin induces apoptosis in PC12 cells; possible implications for the etiology of Parkinson''s disease. Neurochem. Int. 31:207-216, 1997.
176. Ohshima H, Gilibert I and Bianchini F: Induction of DNA strand breakage and base oxidation by nitroxyl anion through hydroxyl radical production. Free Radic. Biol. Med. 26:1305-1313, 1999.
177. Oka M, Hirouchi M, Itoh Y and Ukai Y: Involvement of peroxynitrite and hydroxyradical generated from nitric oxide in hypoxia/reoxygenation injury in rat cerebrocortical slices. Neuropharmacology 39:1319-1330, 2000.
178. Olanow CW: An introduction to the free radical hypothesis in Parkinson’s disease: Ann. Neurol. 32:S2-S9, 1992.
179. Olanow CW: A radical hypothesis for neurodegeneration. Trends Neurosci. 16: 439-444, 1993.
180. Orrenius S, McConkey D, Belloma G and Nicoterm P: Role of Ca2+ in toxic killing. Trends. Pharmacol. Sci. 10:281-285, 1989.
181. Owen AD, Schapira AH, Jenner P and Marsden CD: Oxidative stress and Parkinson''s disease. Ann. N.Y. Acad. Sci. 786:217-23, 1996.
182. Pakkenberg B, Moller A, Gundersen HJ, Mouritzen Dam A and Pakkenberg H: The absolute number of nerve cells in substantia in normal subjects and patients with Parkinson’s disease estimated with an unbiased stereological method. J. Neurol. Neurosurg. Psychiatry 54:30-33, 1991.
183. Palmer RMJ, Ashton DA and Moncada S: Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664-666, 1988.
184. Panfili E, Sandri G and Ernster L: Distribution of glutathione peroxidase and glutathione reductase in rat brain mitochondria. FEBS Lett. 290:35-37, 1991.
185. Pederson TC, Buege JA and Aust SD: Microsomal electron transport. The role of reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase in liver microsomal lipid peroxidation. J. Biol. Chem. 248:7134- 7141, 1973.
186. Pellegrini-Giampietro DE, Cherici G, Alesiani M, Carla V and Moronoi F: Excitatory amino acid release and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage. J. Neurosci. 10:1035-1041, 1990.
187. Perese DA, Ulman J, Viola J, Ewing SE and Bankiewicz KS: A 6-hydroxydopamine-induced selective parkinsonian rat model. Brain Res. 494:285-293, 1989.
188. Peterson RB and Rumack BH: Treating acute acetaminophen poisoning with acetylcysteine. JAMA 237:2406-2407, 1977.
189. Phebus LA, Perry KW, Clemens JA and Fuller RW: Brain anoxia releases striatal dopamine in rats. Life Sci. 38:2447-2453, 1986.
190. Phebus LA and Clemens JA: Effects of transient, global, cerebral ischemia on striatal extracellular dopamine, serotonin and their metabolites. Life Sci. 44:1335-1342, 1989.
191. Przedborski S, Levivier M, Raftopoulos C, Naini AB and Hildebrand J: Peripheral and central pharmacokinetics of apomorphine and its effect on dopamine metabolism in humans. Mov. Disord. 10:28-36, 1995.
192. Qian ZM and Tang PL: Mechanisms of iron uptake by mammalian cells. Biochim. Biophys. Acta 1269:205-214, 1995.
193. Radi R, Beckman JS, Bush KM and Freeman BA: Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch. Biochem. Biophys. 288:481-7, 1991.
194. Rafael H, Moromizato P and Ayulo V: The dopamine transporter gene and PD in a Chinese population. Neurology. 52:429-430, 1999.
195. Rajput AH, Rozdilsky B and Rajput A: Accuracy of clinical diagnosis in Parkinsonism-a prospective study. Can. J. Neurol. Sci. 18:275-278, 1991.
196. Rauhala P, Khaldi A, Mohanakumar KP and Chiueh CC: Apparent role of hydroxyl radicals in oxidative brain injury induced by sodium nitroprusside. Free Radic. Biol. Med. 24:1065-1073, 1998.
197. Reif DW and Simmons RD: Nitric oxide mediates iron from ferritin. Arch. Biochem. Biophys. 283:537-541, 1990.
198. Reith ME, Xu C and Chen NH: Pharmacology and regulation of the neuronal dopamine transporter. Eur. J. Pharmacol. 324:1-10, 1997.
199. Richter C, Gogvadze V, Laffranchi R, Schlapbach R, Schweizer M, Suter M, Walter P and Yaffee M: Oxidants in mitochondria: from physiology to disease. Biochim. Biophys. Acta. 1271:67-74, 1995.
200. Riederer P, Sofic E, Rausch WD, Schmidt B, Reynolds GP, Jellinger K and Youdim MB: Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J. Neurochem. 52:515-520, 1989.
201. Rinne JO, Ruottinen H, Bergman J, Haaparanta M, Eronen E, Sonninen P and Solin O: A novel dopamine transporter PET ligand, [18F]CFT, in assessing disability in Parkinson’s disease. Mov. Disord. 13:174, 1998.
202. Rogers NE and Ignarro LJ: Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine, Biochem. Biophys. Res. Commun. 189:242-249, 1992.
203. Romslo I and Flatmark T: Energy dependent accumulation of iron by isolated liver mitochondria. Biochem. Biophys. Acta. 305:29-40, 1973.
204. Rosen DR, Siddique T, Patterson D, Figlewicz DA and Sapp P: Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59-62, 1993.
205. Rosenbegr PA: Catecholamine toxicity in cerebral cortex of dissociated cell culture. J. Neurosci. 8:2887-2894, 1988.
206. Roth RH: CNS dopamine autoreceptors: distribution, pharmacology, and function. Ann. N. Y. Acad. Sci. 430:27-54, 1984.
207. Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kunci PW, Kanai Y, Hediger MA, Wang Y, Schielke Jp and Welty DF: Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675-686, 1996.
208. Rouault TA and Klausner RD: Iron-sulfur clusters as biosensors of oxidants and iron. Trends Biochem. Sci. 21:174-177, 1996.
209. Saito K, Yoshioka H, Kazama S and Cutler RG: Release of nitric oxide from a spin trap, N-tert-butyl-alpha-phenylnitrone, under various oxidative conditions. Biol. Pharm. Bull. 21:401-404, 1998.
210. Sam EE and Verbeke N: Free radical scavenging properties of apomorphine enantiomers and dopamine: possible implication in their mechanism of action in parkinsonism. J. Neural. Transm. Park. Dis. Dement. Sect. 10:115-127, 1995.
211. Santiago M, Matarredona ER, Granero L, Cano J and Machado A: Neuroprotective effect of the iron chelator desferrioxamine against MPP+ toxicity on striatal dopaminergic terminals. J. Neurochem. 68:732-738, 1997.
212. Sawada H, Ibi M, Kihara T, Urushitani M, Akaike A, Kimura J and Shimohama S: Dopamine D2-type agonists protect mesencephalic neurons from glutamate neurotoxicity: mechanisms of neuroprotective treatment against oxidative stress. Ann. Neurol. 44:110-119, 1998.
213. Scatton B, Monfort JC, Javory-Agid F and Agid Y: Neurochemistry if monoaminergic neurons in Parkinson’s disease. In Catecholamines: Neuropharmacology and Central Nervous System Therapeutic Aspects, pp. 43-52. Alan R. Liss, Inc. New York, 1984.
214. Schapira AH: Evidence for mitochondrial dysfunction in Parkinson''s disease--a critical appraisal. Mov. Disord. 9:125-38, 1994.
215. Schulz JB and Beal MF: Neuroprotective effects of free radical scavengers and energy repletion in animal models of neurodegenerative disease. Ann. N. Y. Acad. Sci. 765:100-110, 1995.
216. Seisjo BK: Historical review: calcium, ischemia, and death of brain cells. Ann. N.Y. Acad. Sci. 522:638-661, 1988.
217. Shaw P: Excitotoxicity and motor neurone disease: a review of the evidence. J. Neurol. Sci. 124: 6-13, 1994.
218. Shen and Dryhurst: Iron- and manganese-catalyzed autoxidation of dopamine in the presence of L-cysteine: possible insights into iron-and manganese-mediated dopaminergic neurotoxicity. Chem. Res. Toxicol. 11:824-837, 1998.
219. Shu Z, Jung M, Beger HG, Marzinzig M, Han F, Butzer U, Bruckner UB and Nussler AK: pH-dependent changes of nitric oxide, peroxynitrite, and reactive oxygen species in hepatocellular damage. Am. J. Physiol. 273:1118-1126, 1997.
220. Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P and Marsden CD: Alterations in glutathione levels in Parkinson''s disease and other neurodegenerative disorders affecting basal ganglia. Ann. Neurol. 36:348-355, 1994.
221. Simonian NA and Coyle JT: Oxidative stress in neurodegenerative diseases. Annu. Rev. Pharmacol. Toxicol. 36:83-106, 1996.
222. Singer TP, Castagnoli N, Ramsay RR and Trevor AJ: Biochemical events in the development of parkinsonism induced by MPTP. J. Neurochem. 49:1-8, 1987.
223. Sloot WN, van der Sluijs-Gelling AJ and Gramsbergen JB: Selective lesions by manganese and extensive damage by iron after injection into rat striatum or hippocampus. J. Neurochem. 62:205-216, 1994
224. Smith MA, Richer-Harris PL, Sayre LM, Backman JS and Perry G: Widesspread peroxynitrite-mediated damage in Alzheimer’s disease. J. Neurosci. 17:2653-257, 1997.
225. Smythies J: Redox mechanisms at the glutamate synapse and their significance: a review. Eur. J. Pharmacol. 370:1-7, 1999.
226. Sofic E, Riederer P, Heinsen H, Beckmann H, Reynolds GP, Hebenstreit G and Youdum MBH: Increased iron(III) and total iron content in post mortem substantia nigra of parkinsonian brain. J. Neural Transm. 74:199-205, 1988.
227. Steranka LR: Stereospecific long-term effects of amphetamine on striatal dopamine neurons in rats. Eur. J. Pharamcol. 76:443-446, 1981.
228. Stibe CMH, Lees AJ, Kempster and Stern GM: Subcutaneous apomorphine in parkinsonian on-off oscillations. Lancet i:403-406, 1988.
229. Synder SH: Nitric oxide: first in a new class of neurotransmitters. Science 257:494-496, 1991.
230. Szabo C: The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 6:79-88, 1996.
231. Theil EC: Regulation of ferritin and transferrin receptor mRNAs. J. Biol. Chem. 265:4771-4774, 1990.
232. Thomas H, Pauline M and Smith BE: Nitric oxide actions in paraventricular nucleus cardiovascular and neurochemical implications. Am. J. Physiol. 266: R306-R313, 1994.
233. Thomas J, Wang J, Takubo H, Sheng J, Jesus SD and Bankiewicz KS: A 6-hydroxydopamine-induced selective parkinsonian rat model: further biochemical and behavioral characterization. Exp Neurol. 126:159-167, 1994.
234. Todd RD: Neural development is regulated by classical neurotransmitters: dopamine D2 receptor stimulation enhances neurite outgrowth. Biol. Psychiatry. 31: 794-807, 1992.
235. Trotti D, Danbolt NC and Volterra A: Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration? TIPS 19:328-334, 1998.
236. Turski L, Bressler K and Retting K-J: Protection of substantia nigra from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists. Nature 349:414-418, 1991.
237. Uhl GR, Hedreen JC and Price DL: Parkinson’s disease: loss of neurons from the ventral tegemental area contralateral to therapeutic surgical lesions. Neurology 35:1215-1218, 1985.
238. Uhl GR, Walther D, Mash D, Faucheux B and Javoy-Agid F: Dopamine transporter messenger RNA in Parkinson’s disease and control substantia nigra neurons. Ann. Neurol. 35:494-498, 1994.
239. Volterra A, Trotti D and Racagni G: Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechanisms. Mol. Pharmacol. 46:986-992, 1994.
240. Wagner GC, Lucot JB, Schuster CR and Seiden LS: Alphamethylpara-tyrosine attenuates and reserpine increases methamphetamine induced neuronal changes. Brain Res. 270:285-288, 1983.
241. Weinberger J, Nieves-Rosa J and Cohen G: Nerve terminal damage in cerebral ischemia: protective effect of alpha-methyl-para-tyrosine. Stroke 16:864-870, 1985.
242. Weiss BG, Werner-Felmayer G, Werner ER, Grunewald K, Wachter H and Hentze MW: Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J. Exp. Med. 180:969-976, 1994.
243. West AR and Galloway MP: Endogenous nitric oxide facilitates striatal dopamine and glutamate efflux in vivo: role of ionotropic glutamate receptor-dependent mechanisms. Neuropharmacology. 36:1571-1581, 1997.
244. Wick MM: Dopamine: a novel antitumor agent active against B-16 melanoma in vivo. J. Invest. Dermatol. 71:163-164, 1978.
245. Williams RJP: Free manganese (II) and iron (II) cations can act as intracellular cell controls. FEBS Lett. 140:3-10, 1982.
246. Wink DA and Mitchell JB: Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radiac. Biol. Med. 25:434-456, 1998.
247. Wolfe L, Olivier N and Sallau D: Prevention of cardiac disease by subcutaneous desferrioxamine in patients with thalassemia major. N. Engl. J. Med. 312:1600-1604, 1985.
248. Xie XY, Zacharias E, Hoff P and Tegtmeier F: Iron channel involvement in anoxic depolarization induced by cardiac arrest in rat brain. J. Cereb. Blood Flow Metab. 15:587-594, 1995.
249. Xie CX, St Pyrek J, Porter WH and Yokel RA: Hydroxyl radical generation in rat brain is initiated by iron but not aluminum, as determined by microdialysis with salicylate trapping and GC-MS analysis. Neurotoxicology. 16:489-496, 1995.
250. Yamamoto BK and Zhu W: The effects of methamphetamine on the production of free radicals and oxidative stress. J. Pharm. Exp. Ther. 287:107-114, 1998.
251. Ye FQ, Allen PS and Martin WRW: Basal ganglia iron content in Parkinson’s disease measured with magnetic resonance. Mov. Disord. 11:243-249, 1996.
252. Yehuda S and Youdim MBH: Brain iron deficiency. Biochemistry and behaviour, in Brain iron. Neurochemical and Behavioural Aspects (Youdim MBH, ed), pp89-114, 1988. Taylor and Francis, London.
253. Yehuda S and Youdim MBH: Brain iron: a lesson from animal studies. Am. J. Clin. Nutr. 56:618-629, 1989.
254. Yoshikawa T, MinamiyamaY, Naito Y and Kondo M: Antioxidant properties of bromocriptine, a dopamine agonist. J. Neurochem. 62:1034-1038, 1994.
255. Youdim MBH, ed. Brain iron: Neurochemical and Behavioural Aspects, 1988. Taylor and Francis, London.
256. Youdim MBH, Ben-Sachar D and Riederer P: Is Parkinson’s disease a progressive siderosis of substantia nigra resulting in iron and melanin induced neurodegeneration? Acta. Neurol. Scand. 126:47-54, 1989.
257. Youdim MBH, Ben-Sachar D and Pollard HB: Iron chelators and calcium channel antagonists as inhibitors of iron induced neuronal lipid peroxidation. Br. J. Pharmacol. 102, 376P, 1991.
258. Youdim MBH, Ben-Sachar D and Riederer P: The possible role of iron in the etiopathology of Parkinson’s disease. Mov. Disord. 8:1-12, 1993a.
259. Youdim MBH and Riederer P: Neurotoxicity of nitric oxide and decompartmentation of ferritin-iron. (Abstr.) J. Neurochem. 61 (Suppl.) S53A, 1993b.
260. Young AB and Fagg GE: Excitatory amino acid receptors in the brain: membrane binding and receptor autoradiographic approaches. Trends Pharmacol. Sci. 11:126-132, 1990.
261. Zeevalk GD and Nicklas WJ: Chemically induced hypoglycemia and anoxia: relationship to glutamate receptor-mediated toxicity in retina. J. Pharmacol. Exp. Ther. 253:1285-1292, 1990.
262. Zetterstrom T, Sharp T, Marsden CA and Ungerstedt U: In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after d-amphetamine. J. Neurochem. 41: 1769-1773, 1983.
263. Zhang J, Price JO, Graham DG and Montine TJ: Secondary excitotoxicity contributes to dopamine-induced apoptosis of dopaminergic neuronal cultures. Biochem. & Biophys. Res. Com. 248:812-816, 1998.
264. Zuddas A, Oberto G and Vaglini F: MK-801 prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinine-induced Parkinsonism in primates. J. Neurochem. 59:733-739, 1992.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊