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研究生:吳家瑋
研究生(外文):Chia-Wei Wu
論文名稱:Pioglitazone的神經保護機制:對於甲基安非他命誘發氧化壓力及粒線體失能之細胞凋亡作用影響
論文名稱(外文):The neuroprotective effects of pioglitazone on oxidative stress and mitochondria dysfunction induced by methamphetamine
指導教授:萬芳榮萬芳榮引用關係林惠卿林惠卿引用關係
指導教授(外文):Fang-Jung WanHui-Chung Lin
學位類別:碩士
校院名稱:國防醫學院
系所名稱:海底醫學研究所
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:2008
畢業學年度:96
語文別:中文
論文頁數:123
中文關鍵詞:甲基安非他命愛妥糖錠
外文關鍵詞:methamphetaminepioglitazone
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甲基安非他命 (Methamphetamine) 為一個非法的成癮藥物,其對人體會造成神經精神方面疾病及神經毒性。甲基安非他命的毒理機制相當複雜。目前所知,甲基安非他命引起細胞損傷的機轉與增加粒腺體及內質網氧化壓力、引起單胺類及非單胺類神經細胞的損傷有關。Thiazolidinediones (例如: pioglitazone、rosiglitazone)作用在細胞核過氧化體增殖劑活化受體(peroxisome proliferator-activated receptor, PPAR-γ)。Thiazolidinediones對於代謝、細胞增生與分化及免疫反應皆有效果。因此,本論文探討pioglitazone對於甲基安非他命毒性是否有保護作用及其可能之訊號路徑。
本實驗利用免疫細胞染色及MTT還原分析法[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay],觀察神經細胞及微小神經膠細胞之型態變化與細胞存活率之情形,利用流式細胞技術探討自由基生成量、細胞粒線體膜電位之變化及細胞凋亡之影響。並利用ERK、PI3K、Bcl-2及GSK-3β抑制劑探討pioglitazone之保護機制。
實驗結果顯示,於大白鼠初級大腦皮質神經細胞有表現PPAR-γ。pioglitazone可活化PPAR-γ,減少甲基安非他命在神經細胞中所誘導的神經毒性、降低ROS產生、改善神經細胞凋亡及粒線體膜電位降低並減少微小神經膠細胞之活化。使用PPAR-γ特異性拮抗劑GW9662可以反轉pioglitazone活化PPAR-γ的保護效果。Pioglitazone保護甲基安非他命誘發神經細胞損傷可能經由PPAR-γ 接受器並透過ERK、PI3K、Bcl-2及GSK-3β這些訊號路徑。然而,甲基安非他命引起微小神經膠細胞之活化可藉pioglitazone經由PPAR-γ 接受器及PI3k/Akt路徑改善。
結論:甲基安非他命可誘發大腦皮質神經細胞粒線體依賴之毒性,包括自由基產生、膜電位改變、細胞凋亡等。Pioglitazone對於甲基安非他命誘發神經損傷中扮演神經保護角色,且ERK、PI3K、Bcl-2及GSK-3β這些訊號路徑可能參與pioglitazone之保護功能。在初級皮質細胞中甲基安非他命所誘導的神經毒性中 pioglitazone可能作為新的保護製劑。
Methamphetamine (MA) is an illicit drug of abuse that can cause neuropsychiatric disorders and neurotoxic damage. The neurotoxic mechanisms of MA are complicated. Thus far, we know that the MA-induced apoptosis is involved in the increased mitochondria oxidative stress and endoplasmic reticulum stress, and can cause neuron cell death in both monoaminergic terminals and non-monoaminergic cells. The thiazolidinediones (e.g., pioglitazone and rosiglitazone) are agonists of the nuclear receptor peroxisome proliferator-activated receptor PPAR-γ. Thiazolidinediones have a wide range of actions on metabolism, cellular proliferation, differentiation, and the immune response of animal. Therefore, we were interested to know whether pioglitazone has neuroprotective effects and its underlying mechanism on MA-induced neurotoxicity.
We used immunocytochemistry and MTT tests to observe the change of neuron and microglia morphology and cell survival. The flow cytometry was used to detect the free radical production, mitochondrial membrane potential dysfunction and apoptosis. The ERK, PI3K, Bcl-2 and GSK-3β inhibitors were used to examine the pathways involved in the neuroprotective role of pioglitazone.
We report here that PPAR-γ is found in rat primary cortical culture. Activation of PPAR-γ by pioglitazone protects rat primary cortical cells against MA-induced neurotoxicity. Pioglitazone reduced MA-induced ROS production and neuronal apoptosis. The drug also restored mitochondrial membrane potential, and reduced activation of microglia. These effects were abolished by the co-treatment of PPAR-γ specific antagonist, GW9662, suggesting that pioglitazone exerts its effects by activating the PPAR-γ pathway. We also demonstrated that Pioglitazone protected against neuronal cell damage possibly via the PPAR-γ, ERK, PI3K, Bcl-2 and GSK-3β pathways. However, pioglitazone was found to diminish the MA-induced microglial activation only via PPAR-γ and PI3K pathways.
We conclude that, in the primary cortical cells, the MA was found to induce mitochondria-dependent neuronal toxicity, including free radical production, mitochondrial membrane potential dysfunction and apoptosis. Pioglitazone plays a neuroprotective role on MA-induced neurotoxicity, possibly through ERK, PI3K, Bcl-2 and GSK-3β pathways. Thus, pioglitazone may serve as a new therapeutic agent for treatment of MA-induced neurotoxicity.
【碩士論文目次】 頁次
正文目錄………………………………………………………………………... I
圖目錄………………………………………………………………………..VIII
中文摘要……………………………………………………………………….XI
英文摘要…………………………………………………………………......XIII
第一章 緒論…………………………………………………………………….1
第一節 甲基安非他命 (methamphetamine) 簡介…………………...1
壹、 甲基安非他命藥理作用及機轉…………………….…1
一、 甲基安發他命在中樞神經系統之作用………...1
二、 甲基安非他命在周邊神經系統之作用…...........2
貳、 甲基安非他命相關作用與毒性……………………….3
一、 甲基安非他命在粒線體之作用…………….…..3
二、 甲基安非他命在微小神經膠細胞之毒性……...5
三、 甲基安非他命在細胞骨架之影響.......................6
第二節 細胞凋亡 (apoptosis)…………………………………...….…7
壹、 細胞壞死與細胞凋亡 (Necrosis and apoptosis)……...7
貳、 粒線體在細胞凋亡扮演之角色……………….………8
參、 劊蛋白酶的活化作用 (Activation of caspases)……..10
肆、 Bcl-2家族 (Bcl-2 family) 蛋白質的表現…………..12
伍、 Glycogen synthase kinase-3β的表現………..……….15
第三節 甲基安非他命誘發之細胞凋亡…………………………..…16
第四節 神經保護劑- Pioglitazone………………………………...…17
壹、 PPAR-γ agonists之作用及機轉……………………...18
貳、 PPAR-γ agonists與腦部神經之相關性……………...19
參、 PPAR-γ agonists之相關應用………………………...20
肆、 PPAR-γ agonists之訊號傳遞路徑……...……………25
第二章 研究目的……………………………………………………………...27
第三章 材料與方法…………………………………………………………...28
第一節 實驗動物……………………………………………………..28
第二節 實驗方法……………………………………………………..28
壹、 大腦皮質之混合膠細胞初代培養 (Primary cortical mix glial culture)……………………………………...28
貳、 藥物處理……………………………………………...29
參、 細胞存活率測試…………………………….………..30
一、 相位差顯微鏡 (phase-contrast microscope)…..31
二、 細胞存活率之測定:MTT 還原分析法…….…32
肆、 細胞免疫染色 (Immunocytochemical staining)……..33
伍、 亞二倍體分析 (Hypoploidy Analysis)………………34
陸、 細胞內活性氧物質 (intracellular reactive oxygen species; ROS) 之測定法……………………………..35
一、 細胞內之 superoxide 測定 (Dihydroethidium ; DHE)…………………………………………...35
二、 NBT 還原試驗 (Nitro blue tetrazolium reduction test)……………………………………………..36
柒、 粒線體膜電位測定…………………………………...37
第三節 資料之統計與分析…………………………………………..38
第四章 實驗結果……………………………………………………………...39
第一節 於大白鼠初級大腦皮質神經細胞有表現PPAR-γ…………39
第二節 pioglitazone對甲基安非他命誘發初級大腦皮質神經細胞之神經毒性具有保護作用…………………………………….39
壹、 pioglitazone能顯著增加甲基安非他命誘發神經毒性之初級大腦皮質神經細胞存活率…………………...39
貳、 pioglitazone對甲基安非他命誘發微小神經膠細胞的活化有保護作用……………………………………...41
參、 pioglitazone降低甲基安非他命誘發初級大腦皮質神經細胞之凋亡………………………………………...42
肆、 pioglitazone降低甲基安非他命造成之初級大腦皮質神經細胞自由基的釋放……………………………...42
伍、 pioglitazone回復甲基安非他命所造成粒線體膜電位的改變………………………………………………...44
第三節 pioglitazone之神經保護作用與PPAR-γ接受器之關聯……44
壹、 pioglitazone藉由PPAR-γ接受器增加初級大腦皮質神經細胞之存活率……………………………………...44
貳、 pioglitazone藉由PPAR-γ接受器改善微小神經膠細胞的活化………………………………………………...46
參、 pioglitazone藉由PPAR-γ接受器減少大腦皮質神經細胞凋亡………………………………………………...47
肆、 pioglitazone藉由 PPAR-γ接受器抑制大腦皮質神經細胞自由基釋放……………………………………...47
伍、 pioglitazone藉由 PPAR-γ接受器回復甲基安非他命所造成粒線體膜電位改變…………………………...49
第四節 pioglitazone之神經保護作用與ERK pathway之關聯……..50
壹、 pioglitazone可藉由ERK pathway 增加初級大腦皮質神經細胞之存活率…………………………………...50
貳、 pioglitazone無法藉由 ERK pathway改善微小神經膠細胞的活化…………………………………………...51
參、 pioglitazone藉由ERK pathway減少大腦皮質神經細胞凋亡………………………………………………...52
肆、 pioglitazone藉由 ERK pathway 抑制大腦皮質神經細胞自由基釋放………………………………………...53
伍、 pioglitazone藉由 ERK pathway改善甲基安非他命所造成粒腺體膜電位降低……………………………...55
第五節 pioglitazone神經保護作用與 PI3K-Akt pathway 之關聯...56
壹、 pioglitazone藉由 PI3K-Akt pathway 增加大腦皮質神經細胞之存活……………………………………...…56
貳、 pioglitazone藉由PI3K-Akt pathway改善微小神經膠細胞的活化…………………………………………...57
參、 pioglitazone藉由 PI3K-Akt pathway 減少初級大腦皮質神經細胞凋亡……………………………………...58
肆、 pioglitazone藉由 PI3K-Akt pathway 抑制大腦皮質神經細胞自由基釋放…………………………………...59
伍、 pioglitazone藉由 PI3K-Akt pathway 改善甲基安非他命所造成粒線體膜電位降低………………………...61
第六節 pioglitazone之神經保護作用與GSK-3β蛋白活性之關聯...62
壹、 pioglitazone藉由抑制GSK-3β蛋白活性增加初級大腦皮質神經細胞之存活率……………………………...62
貳、 pioglitazone無法藉由抑制GSK-3β蛋白活性改善微小神經膠細胞的活化…………………………………...64
參、 pioglitazone可藉由抑制GSK-3β蛋白活性減少大腦皮質神經細胞凋亡……………………………………...64
肆、 pioglitazone藉由抑制GSK-3β蛋白活性抑制大腦皮質神經細胞自由基釋放………………………………...65
伍、 pioglitazone藉由抑制GSK-3β蛋白活性改善甲基安非他命所造成粒線體膜電位降低……………………...67
第七節 pioglitazone之神經保護作用與Bcl-2之關聯……………...68
壹、 pioglitazone藉由 Bcl-2 增加大腦皮質神經細胞之存活率…………………………………………………...68
貳、 pioglitazone無法藉由Bcl-2改善微小神經膠細胞的活化……………………………………………………..70
參、 pioglitazone藉由 Bcl-2 減少初級大腦皮質神經細胞凋亡…………………………………………………...70
肆、 pioglitazone 藉由 Bcl-2 抑制初級大腦皮質神經細胞自由基釋放…………………………………………...71
伍、 pioglitazone藉由 Bcl-2 回復甲基安非他命所造成粒腺體膜電位改變……………………………………...73
第五章 討論…………………………………………………………………...75
第一節 探討甲基安非他命對神經細胞的毒性……………………..75
第二節 探討pioglitazone對神經細胞之保護作用………………….77
第三節 探討pioglitazone對於甲基安非他命誘發神經損傷保護機轉…………………………………………………………….78
壹、 探討PPAR-γ在pioglitazone神經保護作用所扮演之角色……………………………………………………...78
貳、 探討ERK路徑在pioglitazone神經保護作用所扮演之角色…………………………………………………...79
參、 探討PI3K-Akt路徑在pioglitazone神經保護作用所扮演之角色……………………………………………...81
肆、 探討GSK-3β蛋白在pioglitazone神經保護作用所扮演之角色………………………………………………...83
伍、 探討Bcl-2在pioglitazone神經保護作用所扮演之角色……………………………………………………...86
第六章 結論…………………………………………………………………...89
第七章 參考文獻…………………………………………………………….115
Angelucci F, Gruber SH, El Khoury A, Tonali PA, Mathe AA. Chronic amphetamine treatment reduces NGF and BDNF in the rat brain. Eur Neuropsychopharmacol 17:756-762, 2007.
Annis MG, Zamzami N, Zhu W, Penn LZ, Kroemer G, Leber B, Andrews DW. Endoplasmic reticulum localized Bcl-2 prevents apoptosis when redistribution of cytochrome c is a late event. Oncogene 20:1939-1952, 2001.
Aoun P, Simpkins JW, Agarwal N. Role of PPAR-gamma ligands in neuroprotection against glutamate-induced cytotoxicity in retinal ganglion cells. Invest Ophthalmol Vis Sci 44:2999-3004, 2003.
Barr AM, Panenka WJ, MacEwan GW, Thornton AE, Lang DJ, Honer WG, Lecomte T. The need for speed: an update on methamphetamine addiction. J Psychiatry Neurosci 31:301-313, 2006.
Beurel E, Jope RS. The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Prog Neurobiol 79:173-189, 2006.
Bijur GN, De Sarno P, Jope RS. Glycogen synthase kinase-3beta facilitates staurosporine- and heat shock-induced apoptosis. Protection by lithium. J Biol Chem 275:7583-7590, 2000.
Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME Cell Survival Promoted by the Ras-MAPK Signaling Pathway by Transcription-Dependent and -Independent Mechanisms. Science 286:1358-1362, 1999.
Boveris A, Costa LE, Poderoso JJ, Carreras MC, Cadenas E. Regulation of mitochondrial respiration by oxygen and nitric oxide. Ann N Y Acad Sci 899:121-135, 2000.
Breidert T, Callebert J, Heneka MT, Landreth G, Launay JM, Hirsch EC. Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson's disease. J Neurochem 82:615-624, 2002.
Brodbeck J, Balestra ME, Saunders AM, Roses AD, Mahley RW, Huang Y. Rosiglitazone increases dendritic spine density and rescues spine loss caused by apolipoprotein E4 in primary cortical neurons. Proc Natl Acad Sci U S A 105:1343-1346, 2008.
Brown JM, Quinton MS, Yamamoto BK. Methamphetamine-induced inhibition of mitochondrial complex II: roles of glutamate and peroxynitrite. J Neurochem 95:429-436, 2005
Brown JM, Yamamoto BK. Effects of amphetamines on mitochondrial function: role of free radicals and oxidative stress. Pharmacol Ther 99:45-53, 2003.
Cadet JL, Jayanthi S, Deng X. Speed kills: cellular and molecular bases of methamphetamine-induced nerve terminal degeneration and neuronal apoptosis. FASEB J 17:1775-1788, 2003.
Cai J, Yang J, Jones DP. Mitochondrial control of apoptosis: the role of cytochrome c. Biochim Biophys Acta 1366:139-149, 1998.
Callahan LA, Stofan DA, Szweda LI, Nethery DE, Supinski GS. Free radicals alter maximal diaphragmatic mitochondrial oxygen consumption in endotoxin-induced sepsis. Free Radic Biol Med 30:129-138, 2001.
Cheng N, Maeda T, Kume T, Kaneko S, Kochiyama H, Akaike A, Goshima Y, Misu Y. Differential neurotoxicity induced by L-DOPA and dopamine in cultured striatal neurons. Brain Res 743:278-283, 1996.
Chen Z, Gibson TB, Robinson F, Silvestro L, Pearson G, Xu B, Wright A, Vanderbilt C, Cobb MH. MAP kinases. Chem Rev 101:2449-2476, 2001.
Chong ZZ, Li F, Maiese K. Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease. Brain Res Brain Res Rev 49:1-21, 2005.
Cimini A, Benedetti E, Cristiano L, Sebastiani P, D'Amico MA, D'Angelo B, Di Loreto S. Expression of peroxisome proliferator-activated receptors (PPARs) and retinoic acid receptors (RXRs) in rat cortical neurons. Neuroscience 130:325-337, 2005a.
Cimini A, Cristiano L, Colafarina S, Benedetti E, Di Loreto S, Festuccia C, Amicarelli F, Canuto RA, Ceru MP. PPARgamma-dependent effects of conjugated linoleic acid on the human glioblastoma cell line (ADF). Int J Cancer 117:923-933, 2005b.
Collino M, Aragno M, Mastrocola R, Gallicchio M, Rosa AC, Dianzani C, Danni O, Thiemermann C, Fantozzi R. Modulation of the oxidative stress and inflammatory response by PPAR-gamma agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion. Eur J Pharmacol 530:70-80, 2006.
Cregan SP, Dawson VL, Slack RS. Role of AIF in caspase-dependent and caspase-independent cell death. Oncogene 23:2785-2796, 2004.
Cristiano L, Cimini A, Moreno S, Ragnelli AM, Paola Ceru M. Peroxisome proliferator-activated receptors (PPARs) and related transcription factors in differentiating astrocyte cultures. Neuroscience 131:577-587, 2005.
Culman J, Zhao Y, Gohlke P, Herdegen T. PPAR-gamma: therapeutic target for ischemic stroke. Trends Pharmacol Sci 28:244-249,2007.
Davidson C, Gow AJ, Lee TH, Ellinwood EH. Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment. Brain Res Brain Res Rev 36:1-22, 2001.
Deng X, Cai NS, McCoy MT, Chen W, Trush MA, Cadet JL. Methamphetamine induces apoptosis in an immortalized rat striatal cell line by activating the mitochondrial cell death pathway. Neuropharmacology 42:837-845, 2002.
Deng X, Ladenheim B, Jayanthi S, Cadet JL. Methamphetamine administration causes death of dopaminergic neurons in the mouse olfactory bulb. Biol Psychiatry 61:1235-1243, 2007.
Drew PD, Storer PD, Xu J, Chavis JA. Hormone regulation of microglial cell activation: relevance to multiple sclerosis. Brain Res Brain Res Rev 48:322-327, 2005.
Dugo L, Collin M, Thiemermann C. Glycogen synthase kinase 3beta as a target for the therapy of shock and inflammation. Shock 27:113-123, 2007.
Du K, Montminy M. CREB is a regulatory target for the protein kinase Akt/PKB. J Biol Chem 273:32377-32379, 1998.
Dwivedi Y, Rizavi HS, Roberts RC, Conley RC, Tamminga CA, Pandey GN. Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects. J Neurochem 77:916-928, 2001.
Embi N, Rylatt DB,Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem 107:519-527, 1980.
Fantegrossi WE, Ciullo JR, Wakabayashi KT, De La Garza R, 2nd, Traynor JR, Woods JH. A comparison of the physiological, behavioral, neurochemical and microglial effects of methamphetamine and 3,4-methylenedioxymethamphe- tamine in the mouse. Neuroscience 151:533-543, 2008.
Fernandez-Gomez FJ, Galindo MF, Gomez-Lazaro M, Yuste VJ, Comella JX, Aguirre N, Jordan J. Malonate induces cell death via mitochondrial potential collapse and delayed swelling through an ROS-dependent pathway. Br J Pharmacol 144:528-537, 2005.
Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR. New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol 47:681-698, 2007.
Franken IH, Booij J, van den Brink W. The role of dopamine in human addiction: from reward to motivated attention. Eur J Pharmacol 526:199-206, 2005.
Fuenzalida K, Quintanilla R, Ramos P, Piderit D, Fuentealba RA, Martinez G, Inestrosa NC, Bronfman M. Peroxisome proliferator-activated receptor gamma up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis. J Biol Chem 282:37006-37015, 2007.
Fuenzalida KM, Aguilera MC, Piderit DG, Ramos PC, Contador D, Quinones V, Rigotti A, Bronfman FC, Bronfman M. Peroxisome proliferator-activated receptor gamma is a novel target of the nerve growth factor signaling pathway in PC12 cells. J Biol Chem 280:9604-9609, 2005.
Fumagalli F, Gainetdinov RR, Valenzano KJ, Caron MG. Role of dopamine transporter in methamphetamine-induced neurotoxicity: evidence from mice lacking the transporter. J Neurosci 18:4861-4869, 1998.
Gillies PS, Dunn CJ. Pioglitazone. Drugs 60:333-343; discussion 344-335, 2000.
Girnun GD, Domann FE, Moore SA, Robbins ME. Identification of a functional peroxisome proliferator-activated receptor response element in the rat catalase promoter. Mol Endocrinol 16:2793-2801, 2002.
Gorman AM, Orrenius S, Ceccatelli S. Apoptosis in neuronal cells: role of caspases. Neuroreport 9:R49-55, 1998.
Hald A, Lotharius J. Oxidative stress and inflammation in Parkinson's disease: is there a causal link? Exp Neurol 193:279-290, 2005.
Harris MH,Thompson CB The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ 7:1182-1191, 2000.
Hanisch UK. Microglia as a source and target of cytokines. Glia 40:140-155, 2002.
Hunter RL, Dragicevic N, Seifert K, Choi DY, Liu M, Kim HC, Cass WA, Sullivan PG, Bing G. Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J Neurochem 100:1375-1386, 2007.
Inestrosa NC, Godoy JA, Quintanilla RA, Koenig CS, Bronfman M. Peroxisome proliferator-activated receptor gamma is expressed in hippocampal neurons and its activation prevents beta-amyloid neurodegeneration: role of Wnt signaling. Exp Cell Res 304:91-104, 2005.
Jayanthi S, Deng X, Bordelon M, McCoy MT, Cadet JL. Methamphetamine causes differential regulation of pro-death and anti-death Bcl-2 genes in the mouse neocortex. FASEB J 15:1745-1752, 2001.
Jayanthi S, Deng X, Noailles PA, Ladenheim B, Cadet JL. Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades. FASEB J 18:238-251, 2004.
Jordan J, Cena V, Prehn JH. Mitochondrial control of neuron death and its role in neurodegenerative disorders. J Physiol Biochem 59:129-141, 2003.
Juhaszova M, Zorov DB, Kim SH, Pepe S, Fu Q, Fishbein KW, Ziman BD, Wang S, Ytrehus K, Antos CL, Olson EN, Sollott SJ. Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113:1535-1549, 2004.
Kiaei M. Peroxisome Proliferator-Activated Receptor-gamma in Amyotrophic Lateral Sclerosis and Huntington's Disease. PPAR Res 2008:418765, 2008.
Kiaei M, Kipiani K, Chen J, Calingasan NY, Beal MF. Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis. Exp Neurol 191:331-336, 2005.
Kiec-Wilk B, Dembinska-Kiec A, Olszanecka A, Bodzioch M, Kawecka-Jaszcz K. The selected pathophysiological aspects of PPARs activation. J Physiol Pharmacol 56:149-162, 2005.
Kim R, Emi M, Tanabe K. Role of mitochondria as the gardens of cell death. Cancer Chemother Pharmacol 57:545-553, 2006.
Kita T, Wagner GC, Nakashima T. Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption. J Pharmacol Sci 92:178-195, 2003.
Klegeris A, McGeer EG, McGeer PL. Therapeutic approaches to inflammation in neurodegenerative disease. Curr Opin Neurol 20:351-357, 2007.
Kowaltowski AJ, Castilho RF, Vercesi AE. Mitochondrial permeability transition and oxidative stress. FEBS Lett 495:12-15, 2001.
Krajewski S, Krajewska M, Shabaik A, Miyashita T, Wang HG, Reed JC. Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol 145:1323-1336, 1994.
Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med 3:614-620, 1997.
Leist M, Jaattela M. Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol 2:589-598, 2001.
Leroy K, Brion JP. Developmental expression and localization of glycogen synthase kinase-3beta in rat brain. J Chem Neuroanat 16:279-293, 1999.
Li X, Wang H, Qiu P, Luo H. Proteomic profiling of proteins associated with methamphetamine-induced neurotoxicity in different regions of rat brain. Neurochem Int 52:256-264, 2008.
Lorenzo HK, Susin SA. Therapeutic potential of AIF-mediated caspase-independent programmed cell death. Drug Resist Updat 10:235-255, 2007.
Lucas JJ, Hernandez F, Gomez-Ramos P, Moran MA, Hen R, Avila J. Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J 20:27-39, 2001.
Luna-Medina R, Cortes-Canteli M, Alonso M, Santos A, Martinez A, Perez-Castillo A. Regulation of inflammatory response in neural cells in vitro by thiadiazolidinones derivatives through peroxisome proliferator-activated receptor gamma activation. J Biol Chem 280:21453-21462, 2005.
Luo Y, Yin W, Signore AP, Zhang F, Hong Z, Wang S, Graham SH, Chen J. Neuroprotection against focal ischemic brain injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. J Neurochem 97:435-448, 2006.
Marchetti P, Hirsch T, Zamzami N, Castedo M, Decaudin D, Susin SA, Masse B, Kroemer G. Mitochondrial permeability transition triggers lymphocyte apoptosis. J Immunol 157:4830-4836, 1996.
Maeshiba Y, Kiyota Y, Yamashita K, Yoshimura Y, Motohashi M, Tanayama S. Disposition of the new antidiabetic agent pioglitazone in rats, dogs, and monkeys. Arzneimittelforschung 47:29-35, 1997.
Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146:3-15, 1995.
Maurer U, Charvet C, Wagman AS, Dejardin E, Green DR. Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell 21:749-760, 2006.
Murphy AN, Fiskum G, Beal MF. Mitochondria in neurodegeneration: bioenergetic function in cell life and death. J Cereb Blood Flow Metab 19:231-245, 1999.
Nethery D, DiMarco A, Stofan D, Supinski G. Sepsis increases contraction-related generation of reactive oxygen species in the diaphragm. J Appl Physiol 87:1279-1286, 1999.
Nordahl TE, Salo R, Leamon M. Neuropsychological effects of chronic methamphetamine use on neurotransmitters and cognition: a review. J Neuropsychiatry Clin Neurosci 15:317-325, 2003.
Nutt DJ. The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry 67 Suppl 6:3-8, 2006.
O'Reilly LA, Strasser A. Apoptosis and autoimmune disease. Inflamm Res 48:5-21, 1999.
Park SW, Yi JH, Miranpuri G, Satriotomo I, Bowen K, Resnick DK, Vemuganti R. Thiazolidinedione class of peroxisome proliferator-activated receptor gamma agonists prevents neuronal damage, motor dysfunction, myelin loss, neuropathic pain, and inflammation after spinal cord injury in adult rats. J Pharmacol Exp Ther 320:1002-1012, 2007.
Pattison LR, Kotter MR, Fraga D, Bonelli RM. Apoptotic cascades as possible targets for inhibiting cell death in Huntington's disease. J Neurol 253:1137-1142, 2006.
Petros AM, Olejniczak ET, Fesik SW. Structural biology of the Bcl-2 family of proteins. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1644:83-94, 2004.
Philchenkov A. Caspases: potential targets for regulating cell death. J Cell Mol Med 8:432-444, 2004.
Robertson JD, Orrenius S. Molecular mechanisms of apoptosis induced by cytotoxic chemicals. Crit Rev Toxicol 30:609-627, 2000.
Rojo AI, Salinas M, Martin D, Perona R, Cuadrado A. Regulation of Cu/Zn-superoxide dismutase expression via the phosphatidylinositol 3 kinase/Akt pathway and nuclear factor-kappaB. J Neurosci 24:7324-7334, 2004.
Ryu NK, Yang MH, Jung MS, Jeon JO, Kim KW, Park JH. Gene expression profiling of rewarding effect in methamphetamine treated Bax-deficient mouse. J Biochem Mol Biol 40:475-485, 2007.
Sanchez Mejia RO, Friedlander RM. Caspases in Huntington's disease. Neuroscientist 7:480-489, 2001.
Santos MJ, Quintanilla RA, Toro A, Grandy R, Dinamarca MC, Godoy JA, Inestrosa NC. Peroxisomal proliferation protects from beta-amyloid neurodegeneration. J Biol Chem 280:41057-41068, 2005.
Satoh T, Furuta K, Suzuki M, Watanabe Y. Prostaglandin J2 and its metabolites promote neurite outgrowth induced by nerve growth factor in PC12 cells. Biochem Biophys Res Commun 258:50-53, 1999.
Schoonjans K, Martin G, Staels B, Auwerx J. Peroxisome proliferator-activated receptors, orphans with ligands and functions. Curr Opin Lipidol 8:159-166, 1997.
Sharma P, Veeranna, Sharma M, Amin ND, Sihag RK, Grant P, Ahn N, Kulkarni AB, Pant HC. Phosphorylation of MEK1 by cdk5/p35 down-regulates the mitogen-activated protein kinase pathway. J Biol Chem 277:528-534, 2002.
Smaili SS, Hsu YT, Carvalho AC, Rosenstock TR, Sharpe JC, Youle RJ. Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling. Braz J Med Biol Res 36:183-190, 2003.
Sokolov BP, Cadet JL. Methamphetamine causes alterations in the MAP kinase-related pathways in the brains of mice that display increased aggressiveness. Neuropsychopharmacology 31:956-966, 2006.
Stence N, Waite M, and Dailey ME. Dynamics of microglial activation: a confocal time-lapse analysis in hippocampal slices. Glia 33: 256-266, 2001.
Storer PD, Xu J, Chavis J, Drew PD. Peroxisome proliferator-activated receptor-gamma agonists inhibit the activation of microglia and astrocytes: implications for multiple sclerosis. J Neuroimmunol 161:113-122, 2005.
Straiko MM, Coolen LM, Zemlan FP, Gudelsky GA. The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain. Neuroscience 144:223-231, 2007.
Stumm G, Schlegel J, Schafer T, Wurz C, Mennel HD, Krieg JC, Vedder H. Amphetamines induce apoptosis and regulation of bcl-x splice variants in neocortical neurons. FASEB J 13:1065-1072, 1999.
Sun W, Qureshi HY, Cafferty PW, Sobue K, Agarwal-Mawal A, Neufield KD, Paudel HK. Glycogen synthase kinase-3beta is complexed with tau protein in brain microtubules. J Biol Chem 277:11933-11940, 2002.
Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell 81:801-809, 1995.
Thomas DM, Francescutti-Verbeem DM, Kuhn DM. The newly synthesized pool of dopamine determines the severity of methamphetamine-induced neurotoxicity. J Neurochem, 2008.
Thomas DM, Walker PD, Benjamins JA, Geddes TJ, Kuhn DM. Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation. J Pharmacol Exp Ther 311:1-7, 2004.
Tureyen K, Kapadia R, Bowen KK, Satriotomo I, Liang J, Feinstein DL, Vemuganti R. Peroxisome proliferator-activated receptor-gamma agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents. J Neurochem 101:41-56, 2007.
Uryu S, Harada J, Hisamoto M, Oda T. Troglitazone inhibits both post-glutamate neurotoxicity and low-potassium-induced apoptosis in cerebellar granule neurons. Brain Res 924:229-236, 2002.
Vercesi AE, Kowaltowski AJ, Grijalba MT, Meinicke AR, Castilho RF. The role of reactive oxygen species in mitochondrial permeability transition. Biosci Rep 17:43-52, 1997.
Volz TJ, Hanson GR, Fleckenstein AE. The role of the plasmalemmal dopamine and vesicular monoamine transporters in methamphetamine-induced dopaminergic deficits. J Neurochem 101:883-888, 2007.
Wada K, Nakajima A, Katayama K, Kudo C, Shibuya A, Kubota N, Terauchi Y, Tachibana M, Miyoshi H, Kamisaki Y, Mayumi T, Kadowaki T, Blumberg RS. Peroxisome proliferator-activated receptor gamma-mediated regulation of neural stem cell proliferation and differentiation. J Biol Chem 281:12673-12681, 2006.
Wallace TL, Vorhees CV, Zemlan FP, Gudelsky GA. Methamphetamine enhances the cleavage of the cytoskeletal protein tau in the rat brain. Neuroscience 116:1063-1068, 2003.
Wang YL, Frauwirth KA, Rangwala SM, Lazar MA, Thompson CB. Thiazolidinedione activation of peroxisome proliferator-activated receptor gamma can enhance mitochondrial potential and promote cell survival. J Biol Chem 277:31781-31788, 2002.
Wu CW, Ping YH, Yen JC, Chang CY, Wang SF, Yeh CL, Chi CW, Lee HC. Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis. Toxicol Appl Pharmacol 220:243-251, 2007.
Xing B, Xin T, Hunter RL, Bing G. Pioglitazone inhibition of lipopolysaccharide-induced nitric oxide synthase is associated with altered activity of p38 MAP kinase and PI3K/Akt. J Neuroinflammation 5:4, 2008.
Yamaguchi H, Ishiguro K, Uchida T, Takashima A, Lemere CA, Imahori K. Preferential labeling of Alzheimer neurofibrillary tangles with antisera for tau protein kinase (TPK) I/glycogen synthase kinase-3 beta and cyclin-dependent kinase 5, a component of TPK II. Acta Neuropathol 92:232-241, 1996.
Yu X, Shao XG, Sun H, Li YN, Yang J, Deng YC, Huang YG. Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus. Brain Res 1200C:146-158, 2008.
Youle RJ, Strasser A The BCL-2 protein family. opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47-59, 2008.
Yuan J, Yankner BA . Apoptosis in the nervous system. Nature 407:802-809, 2000.
Zhao X, Ou Z, Grotta JC, Waxham N, Aronowski J. Peroxisome-proliferator-activated receptor-gamma (PPARgamma) activation protects neurons from NMDA excitotoxicity. Brain Res 1073-1074:460-469, 2006a.
Zhao Y, Patzer A, Herdegen T, Gohlke P, Culman J. Activation of cerebral peroxisome proliferator-activated receptors gamma promotes neuroprotection by attenuation of neuronal cyclooxygenase-2 overexpression after focal cerebral ischemia in rats. FASEB J 20:1162-1175, 2006b.
朱慧珊,顆粒性球群落刺激因子對於甲基安非他命誘發皮質神經細胞內質網壓力及tau過度磷酸化之保護作用,碩士論文,國防醫學院,2007
林怡芬,顆粒性球群落刺激因子的神經保護作用之研究-甲基安非他命誘導之氧化壓力及細胞凋亡,碩士論文,國防醫學院,2007
張為君,各類神經保護製劑對甲基安非他命誘發神經細胞凋亡作用之研究,碩士論文,國防醫學院,2006。
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