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研究生:王維直
研究生(外文):Wei Chih Wang
論文名稱:探討葉酸缺乏對人類肝癌細胞株HepG2細胞所引起的同胱胺酸誘導之氧化和硝化壓力以及氧化修飾性蛋白所參與之細胞凋亡機制
論文名稱(外文):Folate deficiency-associated apoptosis involve homocysteine-induced oxidative and nitrosative stresses and oxidatively modified proteins in Hep G2 cells
指導教授:劉燦榮劉燦榮引用關係
學位類別:碩士
校院名稱:長庚大學
系所名稱:醫學生物技術研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:44
中文關鍵詞:葉酸氧化壓力氧化修飾性蛋白質
外文關鍵詞:folateoxidative stressoxidatively modified protein
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葉酸是參與同胱胺酸轉換為甲硫胺酸的重要輔因子,因此葉酸缺乏會導致細胞中同胱胺酸的堆積。過去研究顯示,葉酸缺乏會引起Hep G2 cells細胞週期特異性的細胞凋亡,並且指出,葉酸缺乏會透過同胱胺酸的堆積引起H2O2大量產生誘導細胞內氧化壓力,並增加NF-B的活化,使細胞走向凋亡路徑。本研究想更進一步證明,葉酸缺乏是否能透過iNOS表現的增加誘導NO的大量產生使細胞內GSH耗盡,此外,也要證明-catenin的下降是否對NO所誘導的細胞凋亡更敏感。結果發現葉酸缺乏確實會誘導細胞內氧化壓力與硝化壓力的上升,並進一步的利用氧化還原蛋白質體學偵測是否氧化修飾性蛋白質增加於葉酸缺乏的Hep G2細胞,結果指出,有三個carbonylated proteins增加於葉酸缺乏第一週的細胞,包括HSP 60,為粒線體的chaperone protein,可保護粒線體免於氧化壓力的傷害;Protein disulfide isomerase(PDI)為內質網的chaperone,可修復某些氧化態的蛋白質,並影響細胞內鈣離子的平衡;ATP synthetase  chain導致細胞ATP depletion使細胞造成apoptosis。本研究認為葉酸缺乏所引起的細胞凋亡為許多因子所造成,透過Hcy誘導細胞內氧化壓力與硝化壓力的增加,接著造成關鍵性的三個氧化修飾性蛋白質增加,最後都造成葉酸缺乏誘導細胞凋亡的結果。
Folate coenzymes are critical for de novo synthesis of pruine and thymidine, for methionine from homocysteine. Our group has previously reported that folate deficiency could induce a cell cycle-specific apoptosis in Hep G2 cells. Subsequently, we showed folate deficiency-induced oxidative stress and apoptosis was mediated via homocysteine-dependent overproduction of H2O2 and enhanced activation of NF-B. In this study, we further demonstrate that folate deficiency can elicit nitrosative stress by overproducing nitric oxide (NO) mediated via elevated iNOS expression leading to intracellular GSH depletion as reflected by the decreased chloromethyl- fluorescein-diacetate/ GSH fluorescence intensity measured by confocal microscopy. Along the same vein, we also demonstrate that folate deficiency can promote the downregulation of -catenin, a major player in Wnt signaling pathway. This process can also sensitize Hep G2 cells to increased sensitivity to NO-mediated apoptosis. Based on these findings, we conclude that folate deficiency can elicit both oxidative and nitrosative stresses, and thus the proper functions of an array of target proteins can be oxidatively modified by these processes. For this reason, we set out to explore the apoptosis-related target proteins that are being oxidatively modified by the oxidative and nitrosative stresses instigated by folate deficiency in Hep G2 cells using proteomic technique. We found out that three carbonylated proteins were upregulated during an episode of folate deficiency as identified by MALDI-TOF. These proteins included molecular chaperone HSP 60, protein disulfide isomerase (PDI), the mitochondrial complex V subunit, ATP synthetase -chain. Functionally speaking, HSP 60 is a mitochondrial chaperone, and its overexpression can protect mitochondrial function and prevent apoptosis. Thus, its malfunction can render these cells to be susceptible to oxidative stress-mediated apoptosis. Next, PDI an ER chaperone, could interact with damaged target proteins to assist their refolding so that the toxic effective of oxidative stress could be alleviated. The oxidative modification of PDI, the protective function against oxidative stress would be lost. Finally, the oxidative modification of ATP synthetase -chain could also lead to apoptosis due to the depletion of ATP production. Taken together, we suggest that the mechanism for folate deficiency-associated apoptosis is multi-factorials which may initially involve the occurrence of Hcy-mediated oxidative/ nitrosative stresses and consequently resulted in the oxidatively modification of some key proteins, such as HSP 60, PDI and ATP synthetase -chain, via carbonylation reaction. The oxidative modification of these target proteins can ultimately lead to the apoptotic cell death via the drastic changes of their proper conformation caused by oxidative/ nitrosative stresses instigated by folate deficiency.
目 錄
縮寫表…………………………………...………………………………iii
中文摘要…………………………………...……………………………iv
英文摘要………………………………………………………………....v
目錄………………..……………………………………………………vii
第一章 簡介………………………………………………………… 1
1.1 葉酸…………………………………...…...…...……………. 2
1.2 葉酸缺乏與氧化壓力(Oxidative stress)之相關性……..….... 3
1.3 葉酸缺乏與硝化壓力(Nitrosative stress)之相關性……….... 5
1.4 氧化還原蛋白質體學 (Redox proteomics) ...…........………. 7
1.4.1 氧化修飾性蛋白質 (Oxidatively modified proteins) ... 8
1.4.1.1 Carbonylation…….......................….…………. 8
1.4.1.2 Nitration……...................................…………. 10
1.4.1.3 Glutathionylation……..................…...………. 10
1.4.1.4 S-nitrosylation…….........................…………. 10
1.5 葉酸缺乏於蛋白質體學之研究.......................................….. 11
1.6 研究目的(Specific Aims) .....................................…………. 13
第二章 材料與方法……………….....……………………………. 15
2.1 實驗材料……………………………………………...…… 15
2.1.1 細胞株與細胞培養基……………………...…..…… 15
2.2 實驗方法……………………………………………...…… 16
2.2.1 Cell culture………………………………..........…… 16
2.2.2 細胞內ROS的偵測…………………................…… 16
2.2.3 細胞內Nitric Oxide (NO)的偵測………...........…… 16
2.2.4 Mitochondrial membrane potential (Δm)的偵測….. 17
2.2.5 細胞內GSH content的偵測……………….......…… 17
2.2.6 Western blot…………………..............................…… 18
2.2.7 Two-dimensional electrophoresis偵測氧化修飾性蛋白質….............................................................................. 18
2.2.8 Silver stain………………………………............…… 19
2.2.9 In-gel digestion…………………..........…………...… 19
2.2.10 MALDI-TOF質譜分析………………...…......…… 19
2.2.11 測定細胞內ATP之含量………………...........…… 19
2.2.12 Immunofluorescence stain………………….......… 20
第三章 結果………...……………………..………………………. 21
3.1 葉酸缺乏對人類肝癌細胞株Hep G2細胞內ROS產生之影響…………………………………………………………. 21
3.2 葉酸缺乏對人類肝癌細胞株Hep G2細胞Δm之影響… 21
3.3 人類肝癌細胞株Hep G2細胞於葉酸缺乏下造成nitrosative stress之影響……………………...………………………. 23
3.4 葉酸缺乏對人類肝癌細胞株Hep G2細胞內GSH含量之影響…………………………………………………………. 23
3.5 利用DNPH與二維電泳之Western blot分析Hep G2細胞於葉酸缺乏下產生的氧化修飾性蛋白質………………..…. 23
3.6 偵測細胞內ATP的含量…………………….……………. 24
3.7 免疫螢光染色偵測葉酸缺乏細胞內PDI與HSP60蛋白質的表現……………………..………………………………. 24
第四章 討論………...……………………..………………………. 26
4.1 Oxidative stress和Nitrosative stress與葉酸缺乏誘導之cell apoptosis……...……..……………..………………………. 26
4.2 氧化修飾性蛋白質與葉酸缺乏誘導cell apoptosis之相關性……...……………………..……...……………………. 28
4.2.1 ATP synthetase  chain……………………………. 28
4.2.2 Heat shock protein 60………...……………………. 28
4.2.3 Protein disulfide isomerase……..……...………….. 29
第五章 結論………...……………………..………………………. 31
第六章 參考文獻….……………………..………………………... 32
第七章 圖表….………………...…..……………………...……..... 40
Bajo M, Fruehauf J, Kim SH, Fountoulakis M, Lubec G. Proteomic evaluation of intermediary metabolism enzyme proteins in fetal Down's syndrome cerebral cortex. Proteomics. 2: 1539–46, 2002.

Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc. Natl. Acad. Sci. U. S. A. 87: 1620–24, 1990.

Bernardi P, Scorrano L, Colonna R, Petronilli V, Lisa FD. Mitochondria and cell death. Eur. J. Biochem. 264: 687–701, 1999.

Brown KS, Huang Y, Lu ZY, Jian W, Blair IA, Whitehead AS. Mild folate deficiency induces a proatherosclerotic phenotype in endothelial cells. Atherosclerosis. 189: 133–41, 2006.

Brown KS, Kluijtmans LAJ, Young IS, Woodside J, Yarnell JWG, McMaster D, Murray L, Evans AE, Boreham CA, McNulty H, Strain JJ, Mitchell LE, Whitehead AS. Genetic evidence that nitric oxide modulates homocysteine the NOS3 894TT genotype is a risk factor for hyperhomocystenemia. Arterioscler Thromb Vasc Biol. 23: 1014–20, 2003.

Butterfield DA, Kanski J. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech. Aging Dev. 122: 945–62, 2001.

Butterfield DA, Poon HF, St Clair D, Keller JN, Pierce WM, Klein JB, Markesbery WR. Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: Insights into the development of Alzheimer’s disease. Neurobiol. Dis. 22: 223–32, 2006.

Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunol. Today. 15: 7–10, 1994.

Chanson A, Sayd T, Rock E, Chambon C, Sante-Lhoutellier V, Potier de CG, Brachet P. Proteomic analysis reveals changes in the liver protein pattern of rats exposed to dietary folate deficiency. J. Nutr. 135: 2524–2529, 2005.

Chen CY, Liu TZ, Liu YW, Tseng WC, Liu RH, Lu FJ, Lin YS, Kuo SH, Chen CH. 6-shogaol (alkanone from ginger) induces apoptotic cell death of human hepatoma p53 mutant Mahlavu subline via an oxidative stress-mediated caspase-dependent mechanism. J. Agric. Food. Chem. 55: 948–54, 2007.

Chen H, Zhang SM, Schwarzschild MA, Hernán MA, Logroscino G, Willett WC, Ascherio A. Folate intake and risk of Parkinson's disease. Am. J. Epidemiol. 160: 368–75, 2004.

Chen YH, Huang RFS. Folate deficiency-mediated downregulation of intracellular glutathionine and antioxidant enzymes increases susceptibility of human hepatoma Hep G2 cells to various oxidant stress-induced cytotoxicity. J. Biomed. Lab Sci. 13: 52–7, 2001.

Chern CL, Huang RF, Chen YH, Cheng JT, Liu TZ. Folate deficiency-induced oxidative stress and apoptosis are mediated via homocysteine-dependent overproduction of hydrogen peroxide and enhanced activation of NF-kappaB in human Hep G2 cells. Biomed. Pharmacother. 55: 434–442, 2001.

Clapper ML, Coudry J, Chang WCL. -catenin mediated signaling: a molecular target for early chemopreventive intervention. Mutation Res. 555: 97–105, 2004.

Cunningham CC, Coleman WB, Spach PI. The effects of chronic ethanol consumption on hepatic mitochondrial energy metabolism. Alcohol. 25: 127–36, 1990.

Danishpajooh IO, Gudi T, Chen Y, Kharitonov VG, Sharma VS, Boss GR. Nitric oxide inhibits methionine synthase activity in Vivo and disrupts carbon flow through the folate pathway. J. Biol. Chem. 276: 27296–303, 2001.

Di MD, Bellomo G, Thor H, Nicotera P, Orrenius S. Menadione-induced cytotoxicity is associated with protein thiol oxidation and alteration in intracellular Ca2+ homeostasis. Arch. Biochem. Biophys. 235: 343–350, 1984.

Doshi SN, McDowell IF, Moat SJ, Lang D, Newcombe RG, Kredan MB, Lewis MJ, Goodfellow J. Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide? Arterioscler. Thromb. Vasc. Biol. 21: 1196–1202, 2001.

Esfandiari F, Villanueva JA, Wong DH, French SW, Halsted CH. Chronic ethanol feeding ad folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am. J. Physiol. Gas. Liver Physiol. 289: G54–63, 2005.

Ghezzi P, Bonetto V. Redox proteomics: identification of oxidatively modified proteins. Proteomics. 3: 1145–53, 2003.

Gregory JF, Cuskelly GJ, Shane B, Toth JP, Baumgartner TG., Stacpoole PW. Primed constant infusion with [2H3]serine allows in vivo kinetic measurement of serine turnover, homocysteine remethylation, and transsulfuration processes in human one-carbon metabolism. Am. J. Clin. Nutr. 72: 1535–41, 2000.

Ho PI, Ashline D, Dhitavat S, Ortiz D, Collins SC, Shea TB, Rogers E. Folate deprivation induces neurodegeneration: roles of oxidative stress and increased homocysteine. Neurobiol. Dis. 14: 32–42, 2003.

Huang CC, Hsu PC, Hung YC, Liao YF, Liu CC, Hour CT, Kao MC, Tsay GJ, Hung HC, Liu GY. Ornithine decarboxylase prevents methotrexate-induced apoptosis by reducing intracellular reactive oxygen species production. Apoptosis. 10: 895–907, 2005.

Huang RF, Ho YH, Lin HL, Wei JS, Liu TZ. Folate deficiency induces a cell cycle-specific apoptosis in HepG2 cells. J. Nutr. 129: 25–31, 1999.

Huang RF, Huang SM, Lin BS, Wei JS, Liu TZ. Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells. Life Sci. 68: 2799–2811, 2001.

Huang RFS, Lin HL, Yun HH, Yang CM, Liu TZ. Nutritional folate depletion promotes apoptotic propensity with perturbing calcium homeostasis in human HepG2 cells. J. Biomed. Lab Sci. 11: 71–7, 1999.

Hultberg B, Anderson A, Isakasson A. The cell-damaging effects of low amounts of homocysteine and copper ions in human cell line cultures are caused by oxidative stress. Toxico. 123: 33–40, 1997.

Jaffrey SR, Erdjument-Bromage H, Ferris CD, Tempst P, Snyder SH. Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat. Cell Biol. 3: 193–7, 2001.

James SJ, Basnakian AG, Miller BJ. In vitro folate deficiency induces deoxynucleotide pool imbalance, apoptosis, and mutagenesis in Chinese hamster ovary cells. Cancer Res. 54: 5075–80, 1994.

Joshi R, Adhikari S, Patro BS, Chattopadhyay S, Mukherjee T. Free radical scavenging behavior of folic acid: evidence for possible antioxidant activity. Free Radic. Biol. Med. 30: 1390–99, 2001.

Kashiba-Iwatsuki, M, Kitoh K, Kasahara E, Yu H et al., J. Biochem. (Tokyo). 122: 1208–14, 1997.

Keil U, Bonert A, Marques CA, Scherping I, Weyermann J, Strosznajder JB, Müller-Spahn F, Haass C, Czech C, Pradier L, Müller WE, Eckert A. Amyloid beta-induced changes in nitric oxide production and mitochondrial activity lead to apoptosis. J Biol. Chem. 279: 50310–20, 2004.

Kim BJ, Hood BL, Aragon1 RA, Hardwick JP, Conrads TP, Veenstra TD, Song BJ. Increased oxidation and degradation of cytosolic proteins in alcohol-exposed mouse liver and hepatoma cells. Proteomics. 6: 1250–60, 2006.

Kloosterman J, De JN, Rompelberg CJ, Van Kranen HJ, Kampman E, Ocké MC. Folic acid fortification: prevention as well as promotion of cancer. Ned. Tijdschr. Geneeskd. 150: 1443–8, 2006.

Ko HS, Uehara T, Nomura Y. Role of ubiquilin associated with protein-disulfide isomerase in the endoplasmic reticulum in stress-induced apoptotic cell death. J. Biol. Chem. 277: 35386–92, 2002.

Korolainen MA, Goldsteins G, Alafuzoff I, Koistinaho J, Pirttila T. Proteomic analysis of protein oxidation in Alzheimer’s disease brain. Electrophoresis. 23: 3428–3433, 2002.

Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 186: 464–78, 1990.

Li GM, Presnell SR, Gu L. Folate deficiency, mismatch repair-dependent apoptosis, and human disease. J. Nutr. Biochem. 14: 568–75, 2003.

Lin KM, Lin B, Lian IY, Mestril R, Scheffler IE, Dillmann WH. Combined and individual mitochondrial HSP60 and HSP10 expression in cardiac myocytes protects mitochondrial function and prevents apoptotic cell deaths induced by simulated ischemia-reoxygenation. Circulation. 103: 1787–1792, 2001.

Lind C, Gerdes R, Hamnell Y, Schuppe-Koistinen I, von Löwenhielm HB, Holmgren A, Cotgreave IA. Identification of S-glutathionylated cellular proteins during oxidative stress and constitutive metabolism by affinity purification and proteomic analysis. Arch. Biochem. Biophys. 406: 229–40, 2002

Liu TZ, Hu CC, Chen YH, Stern A, Cheng JT. Differentiation status modulates transcription factor NF-kappaB activity in unstimulated human hepatocellular carcinoma cell lines. Cancer Lett. 151: 49–56, 2000.

Magi B, Ettorre A, Liberatori S, Bini L, Andreassi M, Frosali S, Neri P, Pallini V, Di Stefano A. Selectivity of protein carbonylation in the apoptotic response to oxidative stress associated with photodynamic therapy: a cell biochemical and proteomic investigation. Cell Death Differ. 1: 842–52, 2004.

Mohr S, Hallak H, de Boitte A, Lapetina EG, Brüne B. Nitric oxide-induced S-glutathionylation and inactivation of glyceraldehyde-3-phosphate dehydrogenase. J. Biol. Chem. 274: 9427–30, 1999.

Morin JP, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW. Activation of -catenin/TCF signaling in colon cancer by mutation in -catenin or APC. Science. 275: 1787–90, 1997.

Murray IA, Daniels I, Coupland K, Smith JA, Long RG. Increased activity and expression of iNOS in human duodenal enterocytes from patients with celiac disease. Am. J. Physiol. Gastrointest. Liver Physiol. 283: G319–26, 2002.

Nikitovic D, Holmgren A. S-nitrosoglutathione is cleaved by the thioredoxin system with liberation of glutathione and redox regulating nitric oxide. J. Biol. Chem. 271: 19180–5, 1996.

Okamoto T, Akaike T, Sawa T, Miyamoto Y, van der Vliet A, Maeda H. Activation of matrix metalloproteinases by peroxynitrite-induced protein S-glutathiolation via disulfide S-oxide formation. J. Biol. Chem. 276: 29596–602, 2001.

Olszewski AJ, McCully KS. Homocysteine metabolism and the oxidative modification of proteins and lipids. Free Radic. Biol. Med. 14: 683–93, 1993.

Pak KJ, Chan SL, Mattson MP. Homocysteine and folate deficiency sensitize oligodendrocytes to the cell death-promoting effects of a presenilin-1 mutation and amyloid beta-peptide. Neuromolecular Med. 3: 119–28, 2003.

Poon HF, Hensley K, Thongboonkerd V, Merchant ML, Lynn BC, Pierce WM, Klein JB, Calabrese V, Butterfield DA. Redox proteomics analysis of oxidatively modified proteins in G93A-SOD1 transgenic mice_A model of familial amyotrophic lateral sclerosis. Free Rad. Bio. Med. 29: 453–62, 2005.

Quadri P, Fragiacomo C, Pezzati R, Zanda E, Forloni G, Tettamanti M, Lucca U. Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am. J. Clin. Nutr. 80: 114–22, 2004.

Rabek JP, Boylston III WH, Papaconstantinou J. Carbonylation of ER chaperone proteins in aged mouse liver. Biochem. Biophy. Res. Comm. 305: 566–72, 2003.

Radi R, Cassina A, Hodara R, Quijano C, Castro L. Peroxynitrite reactions and formation in mitochondria. Free Radic. Biol. Med. 33: 1451–64, 2002.

Rajamani R, Muthuvel A, Senthilvelan M, Sheeladevi R. Oxidative stress induced by methotrexate alone and in the presence of methanol in discrete regions of the rodent brain, retina and optic nerve. Toxicol. Lett. 165: 265–73, 2006.

Sadeghian S, Fallahi F, Salarifar M, Davoodi G, Mahmoodian M, Fallah N, Darvish S, Karimi A. Homocysteine, vitamin B12 and folate levels in premature coronary artery disease. BMC. Cardiovasc. Disord. 6: 38–45, 2006.

Schernhammer E, Wolpin B, Rifai N, Cochrane B, Manson JA, Ma J, Giovannucci E, Thomson C, Stampfer MJ, Fuchs C. Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts. Cancer Res. 67: 5553–60, 2007.

Shacter E, Williams JA, Lim M, Levine RL. Differential susceptibility of plasma proteins to oxidative modification: Examination by western blot immunoassay. Free Radic. Biol. Med. 17: 429–37, 1994.

Shen HM, Liu ZG. JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic. Biol. Med. 40: 928–39, 2006.

Singh R, Fouladi-Nashta AA, Li D, Halliday N, Barrett DA, Sinclair KD. Methotrexate induced differentiation in colon cancer cells is primarily due to purine deprivation. J. Cell Biochem. 99: 146–55, 2006.

Steegers-Theunissen RP, Smith SC, Steegers EA, Guilbert LJ, Baker PN. Folate affects apoptosis in human trophoblastic cells. BJOG. 107: 1513–5, 2000.

Tchantchou F. Homocysteine increase folate oxidative brain homocysteine metabolism and various consequences of folate deficiency. J. Alzheimers Dis. 9: 421–7, 2006.

Tettamanti M, Garrì MT, Nobili A, Riva E, Lucca U. Low folate and the risk of cognitive and functional deficits in the very old: the Monzino 80-plus study. J. Am. Coll. Nutr. 25: 502–8, 2006.

Tjiattas L, Ortiz DO, Dhivant S, Mitton K, Rogers E, Shea TB. Folate deficiency and homocysteine induce toxicity in cultured dorsal root ganglion neurons via cytosolic calcium accumulation. Aging Cell. 3: 71–6, 2004.

Wang H, MacNaughton WK. Overexpressed -catenin blocks nitric oxide-induced apoptosis in colonic cancer cells. Cancer Res. 65: 8604–7, 2005.

Welch GN, Upchurch GR, Farivar RS, Pigazzi A, Vu K, Brecher P, Keaney JF, Loscalzo J. Homocysteine-induced nitric oxide production in vascular smooth-muscle cells by NF-kappa B-dependent transcriptional activation of Nos2. Proc. Assoc. Am. Physicians. 110: 22–31, 1998.

Zhan X, Desiderio DM. The human pituitary nitroproteome: detection of nitrotyrosyl-proteins with two-dimensional Western blotting, and amino acid sequence determination with mass spectrometry. Biochem. Biophy. Res. Comm. 325: 1180–6, 2004.

Wiseman DA, Wells SM, Wilham J, Hubbard M, Welker JE, Black SM. Endothelial response to stress from exogenous Zn2+ resembles that of NO-mediated nitrosative stress, and is protected by MT-1 overexpression. Am. J. Physiol. Cell Physiol. 291: C555–68, 2006.

Zhang Y, Soboloff J, Zhu Z, Berger SA. Inhibition of Ca2+ influx is required for mitochondrial reactive oxygen species-induced endoplasmic reticulum Ca2+ depletion and cell death in leukemia cells. Mol Pharmacol. 70: 1424–34, 2006.
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