系統識別號 U0026-0812200914001684
論文名稱(中文) 細胞外基質合成酵素lysyl oxidase和prolyl 4-hydroxylase在人類腹主動脈瘤平滑肌細胞的表現
論文名稱(英文) The expression of extracellular matrix synthetic enzymes, lysyl oxidase and prolyl 4-hydroxylase, in human abdominal aortic aneurysm-derived vascular smooth muscle cells
校院名稱 成功大學
系所名稱(中) 細胞生物及解剖學研究所
系所名稱(英) Institute of Cell Biology and Anatomy
學年度 95
學期 2
出版年 96
研究生(中文) 鄔孟陵
研究生(英文) Meng-Ling Wu
學號 t9694101
學位類別 碩士
語文別 英文
論文頁數 64頁
口試委員 口試委員-楊倍昌
中文關鍵字 腹主動脈瘤  血管平滑肌  細胞外基質 
英文關鍵字 abdominal aortic aneurysms  smooth muscle cells  extracellular matrix  prolyl 4-hydroxylase  lysyl oxidase 
中文摘要 腹主動脈瘤在65歲以上人口的發生率為3-9%,一旦動脈瘤發生破裂時,其致死率高達50-70%。腹主動脈瘤主要的特徵包括,動脈管壁中層受到蛋白酵素的破壞,以及平滑肌細胞大量減少。截至目前對於腹主動脈瘤的研究大多在探討細胞外間質的破壞,而導致腹主動脈瘤的形成,但對於生成細胞外間質機制的變化,並不是很清楚。血管平滑肌細胞分泌細胞外間質,負責維持血管的結構。Lysyl oxidase (Lox)為一促進膠原蛋白與彈力蛋白的連結與堆積的酵素;Prolyl 4-hydroxylases (P4H)為膠原蛋白合成過程中的速率調控酵素,兩者都是調控細胞外間質合成與修補的關鍵酵素。現有的證據顯示活性氧分子(ROS)參與了腹主動脈瘤的形成,在本實驗室先前的研究發現,在Angiotensin II的刺激下由人類腹主動脈瘤檢體所培養出的血管平滑肌細胞,其超氧自由基(O2-)的生成與NADPH oxidase酵素活性皆有大量增加。因此我們假設在主動脈瘤培養出的血管平滑肌細胞中,超氧自由基的增加會對於Lox和P4H的表現或活性造成影響。本實驗利用由腹主動脈瘤檢體培養出的血管平滑肌細胞作為體外實驗的實驗組,並以冠狀動脈繞道手術時在升主動脈打洞所取得的檢體培養出的血管平滑肌細胞做為對照組。利用半定量RT-PCR來偵測三種P4H-α次單元體(α1、α2和α3)及P4H-β、Lox訊息核醣核酸的表現,除此之外也利用免疫轉漬法偵測P4H-β的表現。在腹主動脈瘤及冠狀動脈繞道手術所取得的檢體中,P4H-β次單元體蛋白的表現並無差異。在細胞培養的結果,實驗組及對照組細胞在P4H各次單元體及Lox 訊息核醣核酸的表現皆無顯著差異。而給予實驗組和對照組細胞Angiotensin II的刺激對P4H次單元體和Lox的訊息核醣核酸的表現則亦無影響。另外,以超氧自由基產生劑-LY83583刺激人類主動脈平滑肌細胞,會對P4H-α1次單元體訊息核醣核酸的表現產生抑制。由超氧自由基和一氧化氮的作用而產生的活性氧分子-過氧硝酸根(ONOO-)處理則顯著地抑制人類主動脈平滑肌中P4H-β次單元體蛋白的表現,而且抑制的效果隨著過氧硝酸根劑量的增加而增強,但另一種活性氧分子-過氧化氫對P4H-β次單元體蛋白的表現則沒有影響。由上面這些實驗結果顯示在血管平滑肌細胞中,P4H次單元體的表現會受到氧化壓力的影響而減少,但在目前的實驗條件下,Angiotensin II對於P4H次單元體的表現並無刺激作用,此外,對於Lox及P4H次單元體的表現在人類腹主動脈瘤的檢體中到底有沒有受到影響需要更進一步的確認。
英文摘要 Abdominal aortic aneurysm (AAA) occurs in 3~9% of the population over 65 years of age and exhibits a high mortality rate of 50% to 70% when rupture. Destruction of medial wall by proteinases and smooth muscle cell depletion are prominent characteristics of AAA. The mechanisms of extracellular matrix (ECM) degradation have been examined extensively, but much less are known about the regulatory mechanisms of ECM biosynthesis in AAA. Vascular smooth muscle cells (VSMCs) are responsible for synthesizing ECM proteins and maintaining structural integrity of the vascular wall. Lysyl oxidase (Lox), the enzyme initiating the covalent crosslinking of collagen and elastin in the extracellular space, and prolyl 4-hydroxylases (P4H), the rate-limiting enzyme for collagen biosynthesis, are key enzymes regulating ECM biosynthesis and repair. Reactive oxygen species (ROS) have been shown to be involved in the pathogenesis of AAA. Previous studies in our lab indicated that AAA-derived VSMCs exhibited greater capability of ROS production and higher NAD(P)H oxidase activity upon angiotensin II (Ang II) stimulation. Therefore, we hypothesize that increased ROS may modulate Lox and P4H expression in AAA-derived VSMCs. This study used cultured VSMCs derived from AAA specimens as an in vitro model with VSMC derived from the punctured ascending aortae at coronary artery bypass graft (CABG) surgery as control. The mRNA expression of three P4H-α subunits (α1, α2 and α3), P4H-β, and Lox was examined by semi-quantitative RT-PCR. In addition, P4H-β protein expression was examined by immunoblotting. At tissue level, no difference in P4H-β expression was detected between CABG and AAA specimens. In cultured cells, no significant differences in mRNA expression were detected between AAA- and CABG-derived VSMCs for all P4H subunits and Lox. Ang II treatment had no effects on P4H-α1, P4H-α2, P4H-α3, P4H-β or Lox mRNA expression in both AAA- and CABG-derived VSMCs. In human aortic VSMCs, LY83583, a superoxide anion-generating agent, decreased P4H-α1 mRNA expression. In addition, peroxynitrite, an ROS formed by the reaction between superoxide and nitric oxide, decreased P4H-β expression in a dose-dependent manner whereas H2O2 had no effect. These results suggest that oxidative stress may contribute to decreased P4H subunit expression in VSMCs but Ang II does not appear to be the stimulant under current experimental conditions. Further studies are needed to verify whether the expression of Lox and P4H subunits is affected in human AAA specimens.
論文目次 Chinese Abstract……………………………………………………Ⅱ
Materials and Methods………………………………………………12
Discussion ……………………………………………………………35
References ……………………………………………………………39
Tables …………………………………………………………………62
參考文獻 1.Owens GK. Regulation of differentiation of vascular smooth muscle cells. Physiological Reviews. 1995;75(3):487-517.
2.Johnston KW, Rutherford RB, Tilson MD, Shah DM, Hollier L, Stanley JC. Suggested standards for reporting on arterial aneurysms. Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery. Journal of Vascular Surgery. 1991;13(3):452-458.
3.Grange JJ, Davis V, Baxter BT. Pathogenesis of abdominal aortic aneurysm: an update and look toward the future. Cardiovascular Surgery.1997;5(3):256-265.
4.Thompson RW. Basic science of abdominal aortic aneurysms: emerging therapeutic strategies for an unresolved clinical problem. Current Opinion in Cardiology. 1996;11(5):504-518.
5.Kniemeyer HW, Kessler T, Reber PU, Ris HB, Hakki H, Widmer MK. Treatment of ruptured abdominal aortic aneurysm, a permanent challenge or a waste of resources? Prediction of outcome using a multi-organ-dysfunction score. European Journal of Vascular and Endovascular Surgery. 2000;19(2):190-196.
6.Thompson MM. Controlling the expansion of abdominal aortic aneurysms. The British Journal of Surgery. 2003;90(8):897-898.
7.Scott RA, Ashton HA, Kay DN. Abdominal aortic aneurysm in 4237 screened patients: prevalence, development and management over 6 years. The British Journal of Surgery. 1991;78(9):1122-1125.
8.Wilmink TB, Quick CR, Hubbard CS, Day NE. The influence of screening on the incidence of ruptured abdominal aortic aneurysms. Journal of Vascular Surgery. 1999;30(2):203-208.
9.Lopez-Candales A, Holmes DR, Liao S, Scott MJ, Wickline SA, Thompson RW. Decreased vascular smooth muscle cell density in medial degeneration of human abdominal aortic aneurysms. The American Journal of Pathology. 1997;150(3):993-1007.
10.Rizzo RJ, McCarthy WJ, Dixit SN, Lilly MP, Shively VP, Flinn WR, Yao JS. Collagen types and matrix protein content in human abdominal aortic aneurysms. Journal of Vascular Surgery. 1989;10(4):365-373.
11.Baxter BT, McGee GS, Shively VP, Drummond IA, Dixit SN, Yamauchi M, Pearce WH. Elastin content, cross-links, and mRNA in normal and aneurysmal human aorta. Journal of Vascular Surgery. 1992;16(2):192-200.
12.Dobrin PB, Mrkvicka R. Failure of elastin or collagen as possible critical connective tissue alterations underlying aneurysmal dilatation. Cardiovascular Surgery. 1994;2(4):484-488.
13.Gandhi RH, Irizarry E, Cantor JO, Keller S, Nackman GB, Halpern VJ, Newman KM, Tilson MD. Analysis of elastin cross-linking and the connective tissue matrix of abdominal aortic aneurysms. Surgery. 1994;115(5):617-620.
14.Saraff K, Babamusta F, Cassis LA, Daugherty A. Aortic dissection precedes formation of aneurysms and atherosclerosis in angiotensin II-infused, apolipoprotein E-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23(9):1621-1626.
15.Deng GG, Martin-McNulty B, Sukovich DA, Freay A, Halks-Miller M, Thinnes T, Loskutoff DJ, Carmeliet P, Dole WP, Wang YX. Urokinase-type plasminogen activator plays a critical role in angiotensin II-induced abdominal aortic aneurysm. Circulation Research. 2003;92(5):510-517.
16.Yoshimura K, Aoki H, Ikeda Y, Fujii K, Akiyama N, Furutani A, Hoshii Y, Tanaka N, Ricci R, Ishihara T, Esato K, Hamano K, Matsuzaki M. Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase. Nature Medicine. 2005;11(12):1330-1338.
17.Freestone T, Turner RJ, Coady A, Higman DJ, Greenhalgh RM, Powell JT. Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. Arteriosclerosis, Thrombosis, and Vascula Biology. 1995;15(8):1145-1151.
18.Thompson RW, Parks WC. Role of matrix metalloproteinases in abdominal aortic aneurysms. Annals of the New York Academy of Sciences. 1996;800:157-174.
19.Newman KM, Malon AM, Shin RD, Scholes JV, Ramey WG, Tilson MD. Matrix metalloproteinases in abdominal aortic aneurysm: characterization, purification, and their possible sources. Connective Tissue Research. 1994;30(4):265-276.
20.Dollery CM, McEwan JR, Henney AM. Matrix metalloproteinases and cardiovascular disease. Circulation Research. 1995;77(5):863-868.
21.Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circulation Research. 2003;92(8):827-839.
22.Ferrans VJ. New insights into the world of matrix metalloproteinases. Circulation. 2002;105(4):405-407.
23.Nagase H, Woessner JF, Jr. Matrix metalloproteinases. The Journal of Biological Chemistry. 1999;274(31):21491-21494.
24.Suzuki K, Enghild JJ, Morodomi T, Salvesen G, Nagase H. Mechanisms of activation of tissue procollagenase by matrix metalloproteinase 3 (stromelysin). Biochemistry. 1990;29(44):10261-10270.
25.Nagase H, Enghild JJ, Suzuki K, Salvesen G. Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl)mercuric acetate. Biochemistry. 1990;29(24):5783-5789.
26.Reilly JM, Sicard GA, Lucore CL. Abnormal expression of plasminogen activators in aortic aneurysmal and occlusive disease. Journal of Vascular Surgery. 1994;19(5):865-872.
27.Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. European Journal of Cell Biology. 1997;74(2):111-122.
28.Knox JB, Sukhova GK, Whittemore AD, Libby P. Evidence for altered balance between matrix metalloproteinases and their inhibitors in human aortic diseases. Circulation. 1997;95(1):205-212.
29.Davis V, Persidskaia R, Baca-Regen L, Itoh Y, Nagase H, Persidsky Y, Ghorpade A, Baxter BT. Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms. Arteriosclerosis, Thrombosis, and Vascular Biology.1998;18(10):1625-1633.
30.Thompson RW, Holmes DR, Mertens RA, Liao S, Botney MD, Mecham RP, Welgus HG, Parks WC. Production and localization of 92-kilodalton gelatinase in abdominal aortic aneurysms. An elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages. The Journal of Clinical Investigation. 1995;96(1):318-326.
31.Crowther M, Goodall S, Jones JL, Bell PR, Thompson MM. Increased matrix metalloproteinase 2 expression in vascular smooth muscle cells cultured from abdominal aortic aneurysms. Journal of Vascular Surgery. 2000;32(3):575-583.
32.Yamashita A, Noma T, Nakazawa A, Saito S, Fujioka K, Zempo N, Esato K. Enhanced expression of matrix metalloproteinase-9 in abdominal aortic aneurysms. World Journal of Surgery. 2001;25(3):259-265.
33.McMillan WD, Patterson BK, Keen RR, Shively VP, Cipollone M, Pearce WH. In situ localization and quantification of mRNA for 92-kD type IV collagenase and its inhibitor in aneurysmal, occlusive, and normal aorta. Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15(8):1139-1144.
34.Saito S, Zempo N, Yamashita A, Takenaka H, Fujioka K, Esato K. Matrix metalloproteinase expressions in arteriosclerotic aneurysmal disease. Vascular and Endovascular Surgery. 2002;36(1):1-7.
35.Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT. Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. The Journal of Clinical Investigation. 2002;110(5):625-632.
36.Prockop DJ, Kivirikko KI. Collagens: molecular biology, diseases, and potentials for therapy. Annual Review of Biochemistry. 1995;64:403-434.
37.Myllyharju J. Prolyl 4-hydroxylases, the key enzymes of collagen biosynthesis. Matrix Biology. 2003;22(1):15-24.
38.Vuori K, Pihlajaniemi T, Marttila M, Kivirikko KI. Characterization of the human prolyl 4-hydroxylase tetramer and its multifunctional protein disulfide-isomerase subunit synthesized in a baculovirus expression system. Proceedings of the National Academy of Sciences of the United States of America. 1992;89(16):7467-7470.
39.Vuori K, Pihlajaniemi T, Myllyla R, Kivirikko KI. Site-directed mutagenesis of human protein disulphide isomerase: effect on the assembly, activity and endoplasmic reticulum retention of human prolyl 4-hydroxylase in Spodoptera frugiperda insect cells. The EMBO journal. 1992;11(11):4213-4217.
40.Kivirikko KI, Pihlajaniemi T. Collagen hydroxylases and the protein disulfide isomerase subunit of prolyl 4-hydroxylases. dvances in Enzymology and Related Areas of Molecular Biology. 1998;72:325-398.
41.Kivirikko KI, Helaakoski T, Tasanen K, Vuori K, Myllyla R, Parkkonen T, Pihlajaniemi T. Molecular biology of prolyl 4-hydroxylase. Annals of the New York Academy of Sciences. 1990;580:132-142.
42.Annunen P, Autio-Harmainen H, Kivirikko KI. The novel type II prolyl 4-hydroxylase is the main enzyme form in chondrocytes and capillary endothelial cells, whereas the type I enzyme predominates in most cells. The Journal of Biological Chemistry. 1998;273(11):5989-5992.
43.Nissi R, Autio-Harmainen H, Marttila P, Sormunen R, Kivirikko KI. Prolyl 4-hydroxylase isoenzymes I and II have different expression patterns in several human tissues. The Journal of Histochemistry and Cytochemistry. 2001;49(9):1143-1153.
44.Raveendran M, Senthil D, Utama B, Shen Y, Dudley D, Wang J, Zhang Y, Wang XL. Cigarette suppresses the expression of P4Halpha and vascular collagen production. Biochemical and Biophysical Research Communications. 2004;323(2):592-598.
45.Zhang C, Zhang MX, Shen YH, Burks JK, Zhang Y, Wang J, Lemaire SA, Yoshimura K, Aoki H, Coselli JS, Wang XL. TNF-{alpha} Suppresses Prolyl-4-Hydroxylase {alpha}1 Expression via the ASK1-JNK-NonO Pathway. Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27(8):1760-7.
46.Hornstra IK, Birge S, Starcher B, Bailey AJ, Mecham RP, Shapiro SD. Lysyl oxidase is required for vascular and diaphragmatic development in mice. The Journal of Biological Chemistry. 2003;278(16):14387-14393.
47.Maki JM, Rasanen J, Tikkanen H, Sormunen R, Makikallio K, Kivirikko KI, Soininen R. Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice. Circulation. 2002;106(19):2503-2509.
48.Bruel A, Ortoft G, Oxlund H. Inhibition of cross-links in collagen is associated with reduced stiffness of the aorta in young rats. Atherosclerosis. 1998;140(1):135-145.
49.Rosenbloom J, Abrams WR, Mecham R. Extracellular matrix 4: the elastic fiber. The FASEB Journal. 1993;7(13):1208-1218.
50.Csiszar K. Lysyl oxidases: a novel multifunctional amine oxidase family. Progress in Nucleic Acid Research and Molecular Biology. 2001;70:1-32.
51.Smith-Mungo LI, Kagan HM. Lysyl oxidase: properties, regulation and multiple functions in biology. Matrix Biology. 1998;16(7):387-398.
52.Trackman PC, Bedell-Hogan D, Tang J, Kagan HM. Post-translational glycosylation and proteolytic processing of a lysyl oxidase precursor. The Journal of Biological Chemistry. 1992;267(12):8666-8671.
53.Cronshaw AD, Fothergill-Gilmore LA, Hulmes DJ. The proteolytic processing site of the precursor of lysyl oxidase. The Biochemical Journal. 1995;306 ( Pt 1):279-284.
54.Uzel MI, Scott IC, Babakhanlou-Chase H, Palamakumbura AH, Pappano WN, Hong HH, Greenspan DS, Trackman PC. Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures. The Journal of Biological Chemistry. 2001;276(25):22537-22543.
55.Rodriguez C, Raposo B, Martinez-Gonzalez J, Casani L, Badimon L. Low density lipoproteins downregulate lysyl oxidase in vascular endothelial cells and the arterial wall. Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22(9):1409-1414.
56.Gacheru SN, Thomas KM, Murray SA, Csiszar K, Smith-Mungo LI, Kagan HM. Transcriptional and post-transcriptional control of lysyl oxidase expression in vascular smooth muscle cells: effects of TGF-beta 1 and serum deprivation. Journal of Cellular Biochemistry. 1997;65(3):395-407.
57.Smith-Mungo L, Kagan HM. PKC-MEK-MAPK-dependent signal transduction pathway mediates the stimulation of lysyl oxidase expression by serum and PDGF in rat aortic smooth muscle cells. Journal of Cellular Biochemistry. 2002;85(4):775-784.
58.Raposo B, Rodriguez C, Martinez-Gonzalez J, Badimon L. High levels of homocysteine inhibit lysyl oxidase (LOX) and downregulate LOX expression in vascular endothelial cells. Atherosclerosis. 2004;177(1):1-8.
59.Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circulation Research. 2000;86(5):494-501.
60.Saari H, Suomalainen K, Lindy O, Konttinen YT, Sorsa T. Activation of latent human neutrophil collagenase by reactive oxygen species and serine proteases. Biochemical and Biophysical Research Communications. 1990;171(3):979-987.
61.Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. The Journal of Clinical Investigation. 1996;98(11):2572-2579.
62.Henderson EL, Geng YJ, Sukhova GK, Whittemore AD, Knox J, Libby P. Death of smooth muscle cells and expression of mediators of apoptosis by T lymphocytes in human abdominal aortic aneurysms. Circulation. 1999;99(1):96-104.
63.Miller FJ, Jr., Sharp WJ, Fang X, Oberley LW, Oberley TD, Weintraub NL. Oxidative stress in human abdominal aortic aneurysms: a potential mediator of aneurysmal remodeling. Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22(4):560-565.
64.Paik D, Tilson MD. Neovascularization in the abdominal aortic aneurysm. Endothelial nitric oxide synthase, nitric oxide, and elastolysis. Annals of the New York Academy of Sciences. 1996;800:277.
65.Sakalihasan N, Pincemail J, Defraigne JO, Nusgens B, Lapiere C, Limet R. Decrease of plasma vitamin E (alpha-tocopherol) levels in patients with abdominal aortic aneurysm. Annals of the New York Academy of Sciences. 1996;800:278-282.
66.Gavrila D, Li WG, McCormick ML, Thomas M, Daugherty A, Cassis LA, Miller FJ, Jr., Oberley LW, Dellsperger KC, Weintraub NL. Vitamin E inhibits abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25(8):1671-1677.
67.Daugherty A, Manning MW, Cassis LA. Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. The Journal of Clinical Investigation. 2000;105(11):1605-1612.
68.Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circulation Research. 1994;74(6):1141-1148.
69.Shah PK. Inflammation, metalloproteinases, and increased proteolysis: an emerging pathophysiological paradigm in aortic aneurysm. Circulation. 1997;96(7):2115-2117.
70.Koslowski R, Seidel D, Kuhlisch E, Knoch KP. Evidence for the involvement of TGF-beta and PDGF in the regulation of prolyl 4-hydroxylase and lysyloxidase in cultured rat lung fibroblasts. Experimental and Toxicologic Pathology. 2003;55(4):257-264.
71.Pischon N, Darbois LM, Palamakumbura AH, Kessler E, Trackman PC. Regulation of collagen deposition and lysyl oxidase by tumor necrosis factor-alpha in osteoblasts. The Journal of Biological Chemistry. 2004;279(29):30060-30065.
72.Green RS, Lieb ME, Weintraub AS, Gacheru SN, Rosenfield CL, Shah S, Kagan HM, Taubman MB. Identification of lysyl oxidase and other platelet-derived growth factor-inducible genes in vascular smooth muscle cells by differential screening. Laboratory Investigation. 1995;73(4):476-482.
73.Radi R, Rodriguez M, Castro L, Telleri R. Inhibition of mitochondrial electron transport by peroxynitrite. Archives of Biochemistry and Biophysics. 1994;308(1):89-95.
74.MacMillan-Crow LA, Crow JP, Kerby JD, Beckman JS, Thompson JA. Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(21):11853-11858.
75.Houston M, Chumley P, Radi R, Rubbo H, Freeman BA. Xanthine oxidase reaction with nitric oxide and peroxynitrite. Archives of Biochemistry and Biophysics. 1998;355(1):1-8.
76.Berlett BS, Friguet B, Yim MB, Chock PB, Stadtman ER. Peroxynitrite-mediated nitration of tyrosine residues in Escherichia coli glutamine synthetase mimics adenylylation: relevance to signal transduction. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(5):1776-1780.
77.Ischiropoulos H. Biological tyrosine nitration: a pathophysiological function of nitric oxide and reactive oxygen species. Archives of Biochemistry and Biophysics. 1998;356(1):1-11.
78.Koritzinsky M, Seigneuric R, Magagnin MG, van den Beucken T, Lambin P, Wouters BG. The hypoxic proteome is influenced by gene-specific changes in mRNA translation. Radiotherapy and Oncology. 2005;76(2):177-186.
79.Takahashi Y, Takahashi S, Shiga Y, Yoshimi T, Miura T. Hypoxic induction of prolyl 4-hydroxylase alpha (I) in cultured cells. The Journal of Biological Chemistry. 2000;275(19):14139-14146.
80.Fahling M, Perlewitz A, Doller A, Thiele BJ. Regulation of collagen prolyl 4-hydroxylase and matrix metalloproteinases in fibrosarcoma cells by hypoxia. Comparative Biochemistry and Physiology. Toxicology & Pharmacology. 2004;139(1-3):119-126.
81.Isselbacher EM. Thoracic and abdominal aortic aneurysms. Circulation. 2005;111(6):816-828.
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