蛋白質激

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范智鈞(Chih-Chun Fan) 查詢紙本館藏

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生命科學系

論文名稱

蛋白質激
(Protein kinase C involved in low dose sodium arsenite-mediated heme oxygenase-1 expression)

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摘要(英)

Sodium arsenite is a well-known carcinogen and may cause cardiovascular disease, such as atherosclerosis and blackfoot disease. Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes heme degradation into iron, biliverdin, and carbon monoxide. HO-1 is induced by a variety of agents, such as heme, oxidative stress, heat shock, UV irradiation, and some heavy metals (arsenite and cadmium). HO-1 has been proposed to play a dual role in protecting cells against or stimulating intracellular oxidative injury. We investigated the induction of HO-1 by low doses of sodium arsenite (< 1 micro mol/L) in bovine aortic endothelial cells (BAEC). Our results show that both HO-1 protein and mRNA are significantly induced by treatment of BAEC cells with 1mM sodium arsenite. To examine which pathway or which signaling molecule is involved in low dose sodium arsenite-mediated induction of HO-1, several enzyme inhibitors were adopted in this study. Among these inhibitors, protein kinase C (PKC) inhibitors such as H7, staurosporine, and chelerythrine chloride decreased 1 mM sodium arsenite-induced HO-1 expression, whereas inhibitors of tyrosine kinase, nitric oxide synthase (NOS), extracellular-regulated kinase (ERK), and PI-3 kinase are unable to inhibit HO-1 induction. Furthermore, the translocation of various PKC isoforms is then examined by histoimmunochemical technique. The present results have shown that PKC-eta and PKC-epsilon are apparently translocated from cytosol to membrane after 1 micro mol/L sodium arsenite treatment. Therefore PKC-eta and PKC-epsilon is probably involved in low dose sodium arsenite-indued HO-1 expression in BAEC.

關鍵字(中)

★ 亞砷酸鈉
★ 血色素加氧
★ 蛋白質激

關鍵字(英)

★ sodium arsenite
★ heme oxygenase-1
★ protein kinase C

論文目次

中文摘要 ----------------------------------------------- 3
英文摘要 ----------------------------------------------- 5
緒論 --------------------------------------------------- 7
材料與方法 --------------------------------------------- 15
結果 --------------------------------------------------- 23
討論 --------------------------------------------------- 30
圖表 --------------------------------------------------- 37
參考文獻 ----------------------------------------------- 52

參考文獻

Abraham, N. G., Y. Lavrovsky, M. L. Schwartzman, R. A. Stoltz, R. D. Levere, M. E. Gerritsen, S. Shibahara & A. Kappas: Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity. Proc Natl Acad Sci U S A 1995, 92, 6798-802.
Aposhian: Biochemical toxicology of arsenic. Review of biochemical toxicology 1989, 10, 265-299.
Balla, G., H. S. Jacob, J. Balla, M. Rosenberg, K. Nath, F. Apple, J. W. Eaton & G. M. Vercellotti: Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem 1992, 267, 18148-53.
Barrett, J. C., P. W. Lamb, T. C. Wang & T. C. Lee: Mechanisms of arsenic-induced cell transformation. Biol Trace Elem Res 1989, 21, 421-9.
Bradford, M. M.: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976, 72, 248-54.
Bunker, B. & J. Fleury: Noncardiac surgery in individuals with coronary heart disease. Semin Perioper Nurs 1999, 8, 137-45.
Chen, C., M. Wu, S. Lee, J. Wang, S. Cheng & H. Wu: Atherogenicity and carcinogenicity of high-arsenic artesian well water: mutiple risk factors and related malignant neoplasms of blackfoot disease. Artherosclerosis 1988, 8, 452-460.
Chen, C. C., J. K. Wang, W. C. Chen & S. B. Lin: Protein kinase C eta mediates lipopolysaccharide-induced nitric-oxide synthase expression in primary astrocytes. J Biol Chem 1998, 273, 19424-30.
Chen, C. J., H. Y. Chiou, M. H. Chiang, L. J. Lin & T. Y. Tai: Dose-response relationship between ischemic heart disease mortality and long-term arsenic exposure. Arterioscler Thromb Vasc Biol 1996, 16, 504-10.
Chen, C. J., Y. M. Hsueh, M. S. Lai, M. P. Shyu, S. Y. Chen, M. M. Wu, T. L. Kuo & T. Y. Tai: Increased prevalence of hypertension and long-term arsenic exposure. Hypertension 1995, 25, 53-60.
Chiou, H. Y. Epidemiological studies on inorganic methylation capacity and inorganic induced health effects among residents in the blackfoot disease endemic area and Lanyang Basin in Taiwan. Ph.D. Dissertation. Taipei: National Taiwan University, 1996.
Choi, A. M. & J. Alam: Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Respir Cell Mol Biol 1996, 15, 9-19.
Coceani, F.: Carbon monoxide and dilation of blood vessels [letter; comment]. Science 1993, 260, 739.
Dennery, P. A., H. E. Wong, K. J. Sridhar, P. A. Rodgers, J. E. Sim & D. R. Spitz: Differences in basal and hyperoxia-associated HO expression in oxidant-resistant hamster fibroblasts. Am J Physiol 1996, 271, L672-9.
Durante, W., M. H. Kroll, N. Christodoulides, K. J. Peyton & A. I. Schafer: Nitric oxide induces heme oxygenase-1 gene expression and carbon monoxide production in vascular smooth muscle cells. Circ Res 1997, 80, 557-64.
Elbirt, K. K., A. J. Whitmarsh, R. J. Davis & H. L. Bonkovsky: Mechanism of sodium arsenite-mediated induction of heme oxygenase-1 in hepatoma cells. Role of mitogen-activated protein kinases [published erratum appears in J Biol Chem 1998 Jul 10;273(28):179]. J Biol Chem 1998, 273, 8922-31.
Engler Blum, G., M. Meier, J. Frank & G. A. Muller: Reduction of background problems in nonradioactive northern and Southern blot analyses enables higher sensitivity than 32P-based hybridizations. Anal Biochem 1993, 210, 235-44.
Fan, S. R., I. C. Ho, F. L. Yeoh, C. J. Lin & T. C. Lee: Squalene inhibits sodium arsenite-induced sister chromatid exchanges and micronuclei in Chinese hamster ovary-K1 cells. Mutat Res 1996, 368, 165-9.
Foresti, R., J. E. Clark, C. J. Green & R. Motterlini: Thiol compounds interact with nitric oxide in regulating heme oxygenase-1 induction in endothelial cells. Involvement of superoxide and peroxynitrite anions. J Biol Chem 1997, 272, 18411-7.
Gurley, L. R., R. A. Walters, J. H. Jett & R. A. Tobey: Response of CHO cell proliferation and histone phosphorelation to sodium arsenite. J Toxicol Environ Health 1980, 6, 87-105.
Hartsfield, C. L., J. Alam, J. L. Cook & A. M. Choi: Regulation of heme oxygenase-1 gene expression in vascular smooth muscle cells by nitric oxide. Am J Physiol 1997, 273, L980-8.
Hei, T. K., S. X. Liu & C. Waldren: Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species. Proc Natl Acad Sci U S A 1998, 95, 8103-7.
Heydorn, K.: environmental variation of arsenic levels in human blood determined by neutron activation analysis. Clinica Chimica Acta 1970, 28, 349-357.
Huang, R. N. & T. C. Lee: Cellular uptake of trivalent arsenite and pentavalent arsenate in KB cells cultured in phosphate-free medium. Toxicol Appl Pharmacol 1996, 136, 243-9.
IARC: Carcinogenesis of arsenic compounds. IARC 1980, 23, 37-141.
Keyse, S. M. & R. M. Tyrrell: Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci U S A 1989, 86, 99-103.
Lai, M. S., Y. M. Hsueh, C. J. Chen, M. P. Shyu, S. Y. Chen, T. L. Kuo, M. M. Wu & T. Y. Tai: Ingested inorganic arsenic and prevalence of diabetes mellitus. Am J Epidemiol 1994, 139, 484-92.
Lakka, T. A., R. Salonen, G. A. Kaplan & J. T. Salonen: Blood pressure and the progression of carotid atherosclerosis in middle-aged men. Hypertension 1999, 34, 51-6.
Lee, P. J., J. Alam, G. W. Wiegand & A. M. Choi: Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia. Proc Natl Acad Sci U S A 1996, 93, 10393-8.
Lee, T. C. & I. C. Ho: Modulation of cellular antioxidant defense activities by sodium arsenite in human fibroblasts. Arch Toxicol 1995, 69, 498-504.
Lee, T. C., J. L. Ko & K. Y. Jan: Differential cytotoxicity of sodium arsenite in human fibroblasts and Chinese hamster ovary cells. Toxicology 1989, 56, 289-99.
Lee, T. C., N. Tanaka, P. W. Lamb, T. M. Gilmer & J. C. Barrett: Induction of gene amplification by arsenic. Science 1988, 241, 79-81.
Leffler, C. W., A. Nasjletti, C. Yu, R. A. Johnson, A. L. Fedinec & N. Walker: Carbon monoxide and cerebral microvascular tone in newborn pigs. Am J Physiol 1999, 276, H1641-6.
Li, W. & I. N. Chou: Effects of sodium arsenite on the cytoskeleton and cellular glutathione levels in cultured cells. Toxicol Appl Pharmacol 1992, 114, 132-9.
Li, Y. S., J. Y. Shyy, S. Li, J. Lee, B. Su, M. Karin & S. Chien: The Ras-JNK pathway is involved in shear-induced gene expression. Mol Cell Biol 1996, 16, 5947-54.
Liu, Y. C. & H. Huang: Involvement of calcium-dependent protein kinase C in arsenite-induced genotoxicity in Chinese hamster ovary cells. J Cell Biochem 1997, 64, 423-33.
Lovell, M. A. & J. G. Farmer: Arsenic speciation in urine from humans intoxicated by inorganic arsenic compounds. Hum Toxicol 1985, 4, 203-14.
Lynn, S., J. R. Gurr, H. T. Lai & K. Y. Jan: NADH oxidase activation is involved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells. Circ Res 2000, 86, 514-9.
Lynn, S., J. N. Shiung, J. R. Gurr & K. Y. Jan: Arsenite stimulates poly(ADP-ribosylation) by generation of nitric oxide. Free Radic Biol Med 1998, 24, 442-9.
Maines, M. D.: The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997, 37, 517-54.
Masuya, Y., K. Hioki, R. Tokunaga & S. Taketani: Involvement of the tyrosine phosphorylation pathway in induction of human heme oxygenase-1 by hemin, sodium arsenite, and cadmium chloride. J Biochem Tokyo 1998, 124, 628-33.
McCoubrey, W. K., Jr., T. J. Huang & M. D. Maines: Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 1997, 247, 725-32.
Morton, W. & D. Dunnette: Health effect of environmental arsenic, In arsenic in environment. 1994.
Neuzil, J. & R. Stocker: Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J Biol Chem 1994, 269, 16712-9.
Oberly, T. J., C. E. Piper & D. S. McDonald: Mutagenicity of metal salts in the L5178Y mouse lymphoma assay. J Toxicol Environ Health 1982, 9, 367-76.
Oguro, T., M. Hayashi, S. Nakajo, S. Numazawa & T. Yoshida: The expression of heme oxygenase-1 gene responded to oxidative stress produced by phorone, a glutathione depletor, in the rat liver; the relevance to activation of c-jun n-terminal kinase. J Pharmacol Exp Ther 1998, 287, 773-8.
Primiano, T., T. W. Kensler, P. Kuppusamy, J. L. Zweier & T. R. Sutter: Induction of hepatic heme oxygenase-1 and ferritin in rats by cancer chemopreventive dithiolethiones. Carcinogenesis 1996, 17, 2291-6.
Robinson, J. G. & A. S. Leon: The prevention of cardiovascular disease. Emphasis on secondary prevention. Med Clin North Am 1994, 78, 69-98.
Schmidt, H. H., S. M. Lohmann & U. Walter: The nitric oxide and cGMP signal transduction system: regulation and mechanism of action. Biochim Biophys Acta 1993, 1178, 153-75.
Shan, Y., R. W. Lambrecht, T. Hong Lu & H. L. Bonkovsky: Effects of phenylarsine oxide on expression of heme oxygenase-1 reporter constructs in transiently transfected cultures of chick embryo liver cells. Arch Biochem Biophys 1999, 372, 224-9.
Snyder, S. H., S. R. Jaffrey & R. Zakhary: Nitric oxide and carbon monoxide: parallel roles as neural messengers. Brain Res Brain Res Rev 1998, 26, 167-75.
Stocker, R., Y. Yamamoto, A. F. McDonagh, A. N. Glazer & B. N. Ames: Bilirubin is an antioxidant of possible physiological importance. Science 1987, 235, 1043-6.
Suttner, D. M., K. Sridhar, C. S. Lee, T. Tomura, T. N. Hansen & P. A. Dennery: Protective effects of transient HO-1 overexpression on susceptibility to oxygen toxicity in lung cells. Am J Physiol 1999, 276, L443-51.
Terry, C. M., J. A. Clikeman, J. R. Hoidal & K. S. Callahan: TNF-alpha and IL-1alpha induce heme oxygenase-1 via protein kinase C, Ca2+, and phospholipase A2 in endothelial cells. Am J Physiol 1999, 276, H1493-501.
Tseng, C. H., C. K. Chong, C. J. Chen, B. J. Lin & T. Y. Tai: Abnormal peripheral microcirculation in seemingly normal subjects living in blackfoot-disease-hyperendemic villages in Taiwan. Int J Microcirc Clin Exp 1995, 15, 21-7.
Tseng, W., W. Chen, J. Sung & J. Chen: A clinic study of blackfoot disease in Taiwan, an endemic peripheral vascular disease. Mem Coll Med Natl Taiwan Univ 1961, 7, 1-18.
Tseng, W. P.: Effects and dose--response relationships of skin cancer and blackfoot disease with arsenic. Environ Health Perspect 1977, 19, 109-19.
Tseng, W. P., H. M. Chu, S. W. How, J. M. Fong, C. S. Lin & S. Yeh: Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J Natl Cancer Inst 1968, 40, 453-63.
Wen, W. N., T. L. Lieu, H. J. Chang, S. W. Wuu, M. L. Yau & K. Y. Jan: Baseline and sodium arsenite-induced sister chromatid exchanges in cultured lymphocytes from patients with Blackfoot disease and healthy persons. Hum Genet 1981, 59, 201-3.
Xiao, W., L. Wang, T. Scott, R. E. Counsell & H. Liu: Radiolabeled cholesteryl iopanoate/acetylated low density lipoprotein as a potential probe for visualization of early atherosclerotic lesions in rabbits. Pharm Res 1999, 16, 420-6.
Yachie, A., Y. Niida, T. Wada, N. Igarashi, H. Kaneda, T. Toma, K. Ohta, Y. Kasahara & S. Koizumi: Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest 1999, 103, 129-35.
Yamauchi, H., K. Takahashi, M. Mashiko & Y. Yamamura: Biological monitoring of arsenic exposure of gallium arsenide- and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair. Am Ind Hyg Assoc J 1989, 50, 606-12.
Yang, L., S. Quan & N. G. Abraham: Retrovirus-mediated HO gene transfer into endothelial cells protects against oxidant-induced injury. Am J Physiol 1999, 277, L127-33.
Yih, L. H., H. M. Huang, K. Y. Jan & T. C. Lee: Sodium arsenite induces ATP depletion and mitochondrial damage in HeLa cells. Cell Biol Int Rep 1991, 15, 253-64.
Yih, L. H. & T. C. Lee: Effects of exposure protocols on induction of kinetochore-plus and -minus micronuclei by arsenite in diploid human fibroblasts. Mutat Res 1999, 440, 75-82.

指導教授

李德章(Te-Chang Lee)

審核日期

2000-7-12

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