( 您好!臺灣時間:2022/08/15 23:48
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::


研究生(外文):De-Chang Tsai
論文名稱(外文):Study on the effect of 3-amino-1,2,4-triazole on the cadmium-induces metallothioneins in HepG2 cells
指導教授(外文):Lih-Yuan Lin
外文關鍵詞:metallothioneinHepG2 cell linescadmium
  • 被引用被引用:0
  • 點閱點閱:510
  • 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
Metallothionein (MTs)是一種低分子量、含高量cystein並且容易被重金屬誘導的蛋白質。除了重金屬以外,氧化逆境也是誘導MT基因表現的一個因子。在本篇研究當中,我使用catalase的抑制劑3-amino-1,2,4-triazole (3-AT)來研究鎘在人類肝癌細胞株(HepG2)內對MT基因表現的影響。首先我以北方墨漬法,發現隨著3-AT劑量的提高能夠有效的抑制鎘或鋅所引起的MT基因的表現。 此外,另一種catalase抑制劑,salicylic acid也能夠隨著劑量的提高有效的抑制鎘所引起的MT基因的表現。其次我分析了3-AT 與salicylic acid對鎘進入細胞內的影響,結果顯示隨著salicylic acid劑量的提高能夠有效的減少細胞內鎘的含量,低劑量(10 mM)的3-AT也能夠有效的減少細胞內鎘的含量,然而高劑量(80 mM)的3-AT只能夠稍微減少細胞內鎘的含量。另一方面,我發現高劑量(80 mM)的3-AT在鎘所處理的細胞中,能夠有效的降低細胞增殖以及存活度,而低劑量的3-AT或單獨以鎘做處理,則在細胞增殖以及存活度上沒有明顯的抑制效果。 此外,以過氧化氫與鎘共同處理的細胞並不能夠增強MT的表現。這些結果均顯示3-AT抑制鎘所誘導的MT基因表現,有可能不是借由氧化逆境的產生,而是因為3-AT減少鎘進入細胞所造成的結果。

Metallothioneins (MTs) are a group of low molecular weight proteins which rich in cystein residues, and induced markedly by metal ions. In addition, oxidative stress was also a factor to induce the MT gene expression. Previous reports have been demonstrated that cadmium was able to induce the gene expression of metallothionein (MT), but the underlying mechanisms were not well understood. In this study, we used the catalase inhibitor, 3-amino-1, 2, 4-triazole (3-AT), to investigate the effects of cadmium on the gene expression of MT in human hepatoma cell lines (HepG2). First, we found that 3-AT significantly suppressed the gene expression of MT induced by cadmium or zinc using the Northern blot. 3-AT inhibited the gene expression of MT was a dose-dependent manner. Another catalase inhibitor, salicylic acid, also suppressed the gene expression of MT and shown a dose-dependent manner. Second, we tested the effects of 3-AT and salicylic acid on the intracellular level of cadmium in cadmium treatment cells. The results shown that salicylic acid significantly decreased the intracellular level of cadimium in dose-dependent manner. Low dose of 3-AT (10 mM) significantly decreased the intracellular level of cadmium, however, high dose of 3-AT (80 mM) slightly decreased the intracellular level of cadmium. Third, we found that high concentration of 3-AT (80 mM) significantly decreased the proliferation rate and viability in cadmium treatment cells. Low concentration of 3-AT or cadmium alone exhibited no significant effect in the inhibition of cell proliferation and viability. Furthermore, cotreatment of hydrogen peroxide and cadmium was not able to enhance the gene expression of MT compare with cadmium alone. These results suggested that induction of MT gene expression by cadmium might not mediate the generation of oxidative stress. It is possible that 3-AT decreased the cadmium into the cells and resulted in low intracellular level of cadmium and MT expression.

中文摘要................................ 1
英文摘要................................ 3
緒言.................................... 5
材料與方法.............................. 14
結果.................................... 24
討論.................................... 30
參考資料................................ 36
附圖.................................... 50

Andersen, R. D., Birren, B. W., Ganz, T., Herschman, H. R., and Piletz, J. E.(1983). Molecular-cloning of the rat metallothionein-1 (MT-1) messenger-RNA sequence. DNA-a journal of molecular. 2, 15-22.
Andersen, R. D., Taplitz, S. J., Oberbauer, A. M., Calame, K. L., and Herschman, H. R. (1990). Metal-dependent binding of a nuclear factor to the rat metallothionein-I promoter, Nucleic Acids Res. 18, 6049-6055.
Andrews, G. K. (2000). Regulation of metallothionein gene expression by oxidative stress and metal iones. Biochem. Pharmacol. 59, 95-104.
Arizono, K., Peterson, K. L., and Brady, F. O. (1993).Inhibitors of Ca+2 channels, calmodulin and protein kinase prevent A23187 and other inductions of metallothionein mRNA in EC3 rat hepatoma cells. Life Sci. 53, 1031-1037.
Baba, T., Nakano, H., Tamai, K., Sawamura, D., Hanada, K., Hashimoto, I., and Arima, Y. (1998). Inhibitory effect of beta thujaplicin on ultraviolet B induced apoptosis in mouse keratinocytes, Journal of Investigative Dermatology, 110, 24-28.
Barceloux, D. G. (1999). Zinc, J. Toxicol. Clin. Toxicol. 37, 279-292.
Bauman, J. W., Liu, J., Liu, Y. P., and Klaassen, C. D. (1991). Increase in metallothionein produced by chemicals that induce oxidative stress, Toxicol. App. Pharmacol., 110, 347-354.
Beattie, J. H., Marion, M., Denizeau, F. (1987).The modulation by metallothionein of cadmium-induced cytotoxicity in primary hepatocyte cultures. Toxicology. 44, 329-339.
Blazka, M. E., and Shaikh, Z. A. (1992). Cadmium and mercury accumulation in rat hepatocytes: Interactions with other metal ions. Toxicol. Appl. Pharmacol. 113, 118-125.
Block, C., Freyermuth, S., Beyersmann, D., and Malviya, A. N. (1992). Role of cadmium in actvating nuclear protein kinase C and the enzyme binding to nuclear protein. J. Biol. Chem., 267, 19824-19828.
Brugnera, E., Georgiev, O., Radtke, F., Heuchel, R., Baker,E., Sutherland, G. R., and Schaffner, W. (1994). Cloning, chromosomal mapping and characterization of the human metal-regulatory transcription factor MTF-1. Nucleic Acids Res. 22, 3167-3173.
Burlando, B., Viarengo, A., Pertica, M., Ponzano, E., and Orunesu, M. (1997). Effects of free oxygen radicals on Ca2+ release mechanisms in the sarcoplasmic reticulum of scallop (Pecten jacobaeus) adductor muscle. Cell Calcium. 22, 83-90.
Camhi, S. L., Lee, P., and Choi, A. M. (1995). The oxidative stress response, New Horizons. 3, 170-182.
Cherian, M. G., Apostolova, M. D. (2000). Nuclear localization of metallothionein during cell proliferation and differentiation. Cell Mol Biol. 46, 347-356.
Cotgreave, I. A., and Gerdes, R. G. (1998). Recent trends in glutathione biochemistry-glutathione-protein interactions: a molecular link between oxidative stress and cell proliferation. Biochem. Biophys. Res. Commun. 242, 1-9.
Coyle, P., Philcox, J. C., carey, L. C., and Rofe, A. M. (2002). Metallothionein: multipurpose protein. Cell. Mol. Life. Sci. 59, 627-647.
Dalton, T. P., Li, Q., Bittel, D., Liang, L., and Andrews, G. K. (1996). Oxidative stress activates metal-responsive transcription factoe-1 binding activity. occupancy in vivo of metal response elements in the metallothionein-I gene promoter. J. Biol. Chem. 271, 26233-26241.
Deng, D. X., Ono, S., Koropatnick, J., and Cherian, M. G. (1998b). Metallothionein and apoptosis in the toxic milk mutant mouse, Laboratory Investigation. 78, 175-183.
Dnyanesh, A., Limaye and Zahir, A. Shaikh. (1999). Cytotocicity of cadmium and characteristics of its Transport in cardiomyocytes. Toxicol. Appl. Pharmacol. 154, 59-66.
Dudley, R. E., Svoboda, D. J., and Klaassen, C. D. (1982). Acute exposure to cadmium causes severe liver injury in rats. Toxicol. Appl. Pharmacol. 65, 302-313.
Durner, J., Klessig, D. F. (1996). Salicylic acid is a modulator of tobacco and mammalian catalases. J Biol. Chem. 271, 28492-28501.
Ebadi, M., Leuschen, M. P., Elrefaey, H., Hamada, F. M., and Rojas, P. (1996). The antioxidant properties of zinc and metallothionein, Neurochemistry International. 29, 159-166.
Endo, T., and Shaikh, Z. A. (1993). Cadmium uptake by primary cultures of rat renal cortical epithelial cells: Influence of cell density and other metal ions. Toxicol. Appl. Pharmacol. 121, 203-209.
Fornace, A. J., Schalch, J. H., and Issac, A. J. (1988). Coordinate induction of metallothionein I and II in rodent cells by UV irradiation. Mol. Cell. Biol. 8, 4716-4720.
Fukino, H., Hirai, M., Hsueh, Y. M., Moriyusu, S., and Yamane, Y. (1986). Mechanism of protection by zinc against mercuric chloride toxicity in rats. Effects of zinc and mercury on glutathione metabolism. J. Toxicol. Environ. Health, 19, 75-89.
Furey, W. F., Clancy, L. L., Robbins, A. H., Stout, C. D., Wang, B. C., and Winge, D. R. (1986). Crystal-structure of CD,Zn Metallothionein. Science. 231, 704-710.
Furst, P., Hamer, D., Hackett, R., and Hu, S. (1988) Copper activates metallothionein gene transcription by altering the conformation of a specific DNA binding protein. Cell 55, 705-717.
Ganesan, V., Thomas, G. (2001). Salicylic acid response in rice: influence of salicylic acid on H(2)O(2) accumulation and oxidative stress. Plant science. 160, 1095-1106.
Haidara, K., Moffatt, P., Denizeau, F. (1999). Metallothionein induction attenuates the effects of glutathione depletors in rat hepatocytes. Toxicol Science. 49, 297-305.
Hanada, K., Baba, T., Hashimoto, I., Fukui, R., Watanabe, S. (1993). Possible role of cutaneous metallothionein in protection against photo-oxidative stress epidermal localization and scavenging activity for superoxide and hydroxyl radical. Photodermatol Photoimmunol Photomed. 9, 209-213.
Hart, B. A., Prabhu, R. M., Eneman, J. D., Durieux-Lu C. C., Janssen, A. M., Borm, P. J. (1995). Oxidant resistance of cadmium-adapted human lung fibroblasts. Toxicology. 98, 1-13.
Hellquist, H. B. (1997). Apoptosis in epithelial hyperplastic laryngeal lesions. Acta. Oto-Laryngologica. 527, 25-29.
Hinkle, P. M., and Osborne, M. E. (1994). Cadmium toxicity in rat pheochromocytoma cells; Studies on the mechanism of uptake. Toxicol. Appl. Pharmacol. 124, 91-98.
Hussain, S., Slikker, W., and Ali, S. F. (1996). Role of metallothionein and other antioxidants in scavenging superoxide radicals and their possible role in neuroprotection, Neurochem. Int. 29, 145-152.
Imbert, J., Hamer, D., Zafarullah, M., Culotta, V. C., and Gedamu, L. (1989). Transcription factor-MBF-I interacts with metal regulatory elements of higher eukaryotic metallothionein genes, Mol. Cell. Biol., 9, 5315-5323.
Jeane, M. D., Freitas., Amir, Liba, Rogerio, Meneghini, Joan, Selverstone Valentine, Edith., Butler., and Gralla. (2000). Yeast lacking Cu-Zn superoxide Dismutase show altered iron homeostasis. J. Biol. Chem. 275, 11645-11649.
Koizumi, T., Shirakura, H., Kumagai, H., Tatsumoto, H., Suzuki, K. T. (1996). Mechanism of cadmium-induced cytotocity. In rat Hepatocyte: cadmium-induced active oxygen-related permeability changes of the plasma membrane. Toxicology. 114, 125-134.
Kagi, J. H. R., and Kojima, Y. (1987). Chemistry and Biochemistry of Metallothionein, Experientia (Suppl.), 52, 25-61.
Kagi, J. H. R., and Schaffer, A. (1988). Biochemistry of metallothionein, Biochemistry, 27, 8509-8515.
Kalpana, Ghoshal, Wang, Y. John, F. Sheridan., and Samson, T. Jacob. (1998). Metallothionein induction in response to restraint stress. J. Biol. Chem. 273, 27904-27910.
Karin, M., Cooke, T., Dietlin, T., Haslinger, A., and Heguy, A. (1987). Metal responsive elements act as positive modulators of human metallothionein-IIa enhancer activity, Mol. Cell. Biol. 7, 606-613.
Karin, M., Wong, G., Imbra, R. J., and Heguy, A. (1985). Interleukin-1 regulates human metallothionein gene expression , Mol. Cell. Biol. 5, 2866-2869.
Kershaw, W. C., Iga, T. and Klaassen, C. D. (1990). Ethanol decreases cadmium hepatotoxicity in rats - possible role of hepatic metallothionein induction, Toxicol. App. Pharmacol. 106, 448-455.
Khayat A, Dencker L. (1982). Fetal uptake and distribution of metallic mercury vapor in the mouse: influence of ethanol and aminotriazole. Int J Biol Res Pregnancy. 3, 38-46.
Kiningham, k., and Kasarskis, E. (1998). Antioxidant function of metallothionein, J. Trace Elements in Exper. Med. 11, 219-226.
Klaassen, C. D., Dorian, C. (1995). Protection by zinc-metallothionein (ZnMT) against cadmium-metallothionein-induced nephrotoxicity. Fundam Appl Toxicol. 26, 99-106.
Koizumi, S., Yamada, H., Suzuki, K., and Otsuka, F. (1992). Zinc specific activation of a HeLa cell nuclear protein which interacts with a metal responsive element of the human metallothionein-IIa gene, Eur. J. Biochem., 210, 555-560
Koizumi, T., Shirakura, H., Kumagai, H., Tatsumoto, H., and Suzuk, K. T. (1996). Mechanism of cadmium-induced cytotoxicity in rat hepatocytes: cadmium-induced active oxygen-related permeability changes of the plasma membrane. Toxicology 114, 125-134.
Kondo, Y., Woo, E. S., Michalska, A. E., Choo, K. H. A. and Lazo, J. S. (1995). Metallothionein null cells have increased sensitivity to anticancer drugs. Cancer Research. 55, 2021-2023.
Kondo, Y., Rusnak, J. M., Hoyt, D. G. Settineri, C. E. Pitt, B. R. and Lazo, J. S. (1997). Enhanced apoptosis in metallothionein null cells, Molecular Pharmacology. 52, 195-201.
Krasne, S., Eisenman, G., and Szabo, G. (1971). Freezing and melting of lipid bilayers and the mode of action of nonactin, valinomycin, and gramicidin. Science. 174, 412-415.
Lazo, J. S., and Pitt, B. R. (1995). Metallothioneins and cell death by anticancer drugs, Annual Review of Pharmacology and Toxicology. 35, 635-653.
Lazo, J. S., Kondo, Y., Dellapiazza, D., Michalska, A. E., Choo, K. H. A., and Pitt, B. R. (1995). Enhanced sensitivity to oxidative stress in cultured embryonic cells from transgenic mice deficient in metallothionein-I and metallothionein-II genes, J. Biol. Chem. 270, 5506-5510.
Lazo, J. S., Kuo, S. M., Woo, E. S., and Pitt, B. R. (1998). The protein thiol metallothionein as an antioxidant and protectant against antineoplastic drugs. Chemico-Biological Interactions. 112, 255-262.
Lehman-Mckeeman, L. D., Klaassen, C. D., and Andrews, G. K. (1988). Mechanisms of regulation of rat hepatic metallothionein-I and metallothionein-II levels following administration of zinc, Toxicol. App. Pharmacol., 92, 1-9
Lehman-Mckeeman, L. D., Klaassen, C. D., and Andrews, G. K. (1988).Ontogeny and induction of hepatic isometallothioeins in immature rats, Toxicol. App. Pharmacol., 92, 10-17
Liang, Y. C., Tsai, S. H., Tsai, D. C., Lin-Shiau S.Y., Lin, J. K. (2001). Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-gamma by flavonoids in mouse macrophages. FEBS Lett. 496, 12-18.
Liu, J., Corton, C., Dix, D. J., Liu, Y., Waalkes, M. P., Klaassen, C. D. (2001). Genetic background but not metallothionein phenotype dictates sensitivity to cadmium-induced testicular injury in mice. Toxicol Appl Pharmacol. 176 (1):1-9.
Liu, Y., Liu, J., Habeebu, S. M., Waalkes, M. P., and Klaassen, C. D. (2000). Metallothionein-I/II null mice are sensitive to chromic oral cadmium-induced nephrotoxicity. Toxicol. Sci. 57, 167-176.
Magos, L., Sugata, Y., Clarkson, T. W. (1974). Effect of 3-amino-1,2,4-triazole on mercury uptake by in vitro human blood samples and by whole rats. Toxicol. Appl. Pharmacol. 28, 367-373.
Masao, Sato. and Bremner. (1993). Oxygen free radicals and metallothionein. Free Radical & Medicine. 14, 325-337.
Masters, B. A., Kelly, E. J., Quaife, C. J., Brinster, R. L., and Palmiter, R. D. (1994). Targeted disruption of metallothionein I and II genes increases sensitivity to cadmium. Proc. Natl. Acad. Sci. USA. 91, 584-588.
Meguro, K., Kobayashi, E., Maki, Y. (1987). Acute brain swelling during evacuation of subdural hematoma caused by delayed contralateral extradural hematoma: report of two cases. Neurosurgery. 20, 326-328.
McCormick, C. C., and Lin, L. Y. (1988). Accumulation of Hepatic Zn7 and Zn/Cu Metallothionein in Copper-loaded Chicks: Isolation and Characterization., Hurley-LS Keen-Cl Lonnerdal-B Rucker-RB (Eds.) Trace Elements in Man and Animals 6, Plenum Press, New York and London, 39-40.
Mueller, P. R., Salser, S. J., and Wold, B. (1988). Constitutive and metal inducible protein - DNA interactions at the mouse metallothionein-I promoter examined by in vivo and in vitro footprinting, Genes & Dvelopment, 2, 412-427.
Murakami, K., Routtenberg, A., and Whiteley, M. K. (1987). Regulation of protein kinase C activity by cooperative interaction of Zn+2 and Ca+2., J. Biol. Chem. 262, 3902-3906.
Murakami, K., Irie, K., Morimoto, A., Ohigashi, H., Shindo, M., Nagao, M., Shimizu, T., and Shirasawa, T. (2002). Synthesis, aggregation, neurotoxicity, and secondary structure of various Abeta1-42 mutants of familial Alzheimer's disease at positions 21-23. Biochem Biophys Res Commun. 294, 5-10.
Nagel, W. W., and Vallee, B. L. (1995). Cell cycle regulation of metallothionein in human colonic cancer cells. Proc. Natl. Acad. Sci. U. S. A. 92:579-583.
Nartey, N., Banerjee, D., and Cherian, M. G. (1987). Immunohistochemical localization of metallothionein in human thyroid tumors, American Journal of Pathology, 129, 177-182.
Najer, A., Parnowska, W., Lukasiewicz, A. (1997). New polymerized complexes of amino-triazole with transition metals as potential fungicidal drugs. Acta Pol Pharm. 54, 203-205.
Norbert, Weissmann, Friedrich, Grimminger., Robert, Voswingckel., Jorg, C. Z., and Werner, Seeger. (1998). Nitro blue tetrazolium inhibits but does not mimic hypoxic vasoconstriction in isolated rabbit lungs. American journal of physiology. 274, 721-727.
Nobuhiko, Miura., Yoko, Matsumoto., Shinichi, Miyairi., Shoji, Nishiyama., and Akira, Naganuma. (1999). Protective effects of triterpene compounds against the cytotoxicity of cadmium in HepG2 cells. Molecular Pharmacology. 56, 1324-1328.
Oh, S. H., Deagen, J. T., Whanger, P. D., and Weswig, P. H. (1978). Biological function of metallothionein. V. Its induction in rats by various stress, Am. J. Physiol., 234, E282-285.
Ossola, J. O., Tomaro, M. L. (1995). Heme oxygenase induction by cadmium chloride: evidence for oxidative stress involvement. Toxicology. 104, 141-147.
Palmiter, R. D. (1994). Regulation of metallothionein genes by heavy metals appears to be mediated by a zinc-sensitive inhibitor that interacts with a constitutively active transcription factor, MTF-1, Proc. Natl. Acad. Sci. USA. 91, 1219-1223.
Phillips, J. C., Lake, B. G., Gangolli, S. D., Grasso, P., Lloyd, A. G. (1977). Effects of pyrazole and 3-amino-1,2,4-triazole on the metabolism and toxicity of dimethylnitrosamine in the rat. J Natl. Cancer Inst. 58, 629-633.
Piedboeuf, B., Johnston, C. J., Watkins, R. H., Hudak, B. B., Lazo, J. S., Cherian, M. G., and Horowitz, S. (1994). Increased expression of tissue inhibitor of metalloproteinases (TIMP-I) and metallothionien in murine lungs after hyperoxic exposure, American Journal of Respiratory Cell and Molecular Biology. 10, 123-132.
Plisov, S. Y., Nichiporenko, M. G., Shkapenko, A. L., Kumarev, V. P., Baranova, L. V., and Merkulova, T. I. (1994). The immediate vicinity of mouse metallothionein-I gene contains two sites conferring glucocorticoid inducibility to the heterologous promoter. FEBS Lett. 352, 339-341.
Quest, A. F. G., Bloomenthal, J., Brades, E. S. G., and Bell, R. M. (1992). The regulatory domain of protein kinase C coordinates four atoms of zinc. J. Biol. Chem. 267, 10193-10197.
Radtke, F., Georgiev, O., Muller, H. P., Brugnera, E., and Schaffner, W. (1995). Functional domains of the heavy metal-responsive transcription regulator MTF-1, Nucleic Acids Res., 23, 2277-2286.
Ren, Y. F., and smith, A. (1995). Mechanism of metallothionein gene, regulation by heme, hemopexin: rolrs of protein kinase C, reactive oxygen species, and cis, acting elements, J. Biol. Chem. 270, 23988-23995.
Roesijadi, G., Brubacher, L. L., Unger, M. E., Anderson, R. S. (1997). Metallothionein mRNA induction and generation of reactive oxygen species in molluscan hemocytes exposed to cadmium in vitro.Comp. Biochem physiol. C pharmarcol Toxicology Endocrinol. 118, 171-176.
Rosner, J. L., Aumercier, M. (1990). Potentiation by salicylate and salicyl alcohol of cadmium toxicity and accumulation in Escherichia coli. Antimicrob Agents Chemother. 34, 2402-2406.
Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual. 2nd Ed. Cold Spring Harbor Laboratories, Cold Spring Harbor, New York.
Salmela, K. S., Tsyrlov, I. B., and Lieber, C. S. (2001). Azide inhibits human cytochrome P -4502E1, 1A2, and 3A4. Alcohol Clin Exp Res. 25, 253-260.
Sato, M., Sasaki, M., and Hojo, H. (1993). in Metallothionein III (Suzuki, K.T. and Imura, N., and Kimura, M. eds) pp. 125-150, Birkhauser, Basel.
Searle, P. F., Stuart, G. W., and Palmiter, R. D. (1985). Building a metal-responsive promoter with synthetic regulatory elements, Mol. Cell. Biol., 5, 1480-1489.
Shinogi, M., Sakaridani, M., and Yokoyama, I. (1999).Metallothionein induction in rat liver by dietary restriction or exercise and reduction of exercise-induced hepatic lipid peroxidation, Biol. Pharm. Bull. 22, 132-136.
Shiraishi, N., Taniguchi, S., Hayashi, H., Hiraki, Y., Itano, Y., Kosaka, F., Aono, K., and Noji, S. (1989). Elevation in metallothionein messenger-RNA in rat tissues after exposure to X-irradiation. Toxicol. Appl. Pharmacol. 98, 501-506.
Slater, A. F. G., Nobel, C. S. I., Van den Dbbelstein, D., and Orrenius, S. (1996). Dithiocarbamates and the redox regulation of cell death. Cell Death Differ. 3, 57-62.
Smirnova, I. V., Bittel, D. C., Ravindra, R., Jiang, H., and Andrews, G. K. (2000). Zinc and cadmium can promote rapid nuclear translocation of metal response element-binding transcription factor-1, J. Biol. Chem., 275, 9377-9384.
Smith, J. B., Dwyer, S. D., and Smith, L. (1989). Cadmium evokes inositol polyphosphate formation and calcium mobilization. J. Biol. Chem. 264, 7115-7118.
Stevenson, G. F., Chan, H. M., and Cherian, M. G. (1994). Copper-metallothionein from the toxic milk mutant mouse enhances lipid-peroxidation initiated by an organic hydroperoxide, Toxicol. Appl. Pharmacol. 125, 90-96.
Stuart, G. W., Searle, P. F., and Palmiter, R. D. (1985). Identification of multiple metal regulatory elements in mouse metallothionein-I promoter by assaying synthetic sequences , Nature, 317, 828-831.
Studer, R., Vogt, C. P., Cavigelli, M., Hunziker, P. E., and Kagi, J. H. (1997). Metallothionein accretion in human hepatic cells is linked to cellular proliferation, Biochem. J., Vol 328, p63-67.
Sundaresan, M., Yu, Z.-X., Ferrans, V. J., Irani, K., and Finkel, T. (1995). Requirement for generation of H2O2 for paltelet-derived growth factor signal transduction, Science. 270, 296-299.
Sundelin, K., Jadner, M., Norberg-Spaak, L., Davidsson, A., and Hellquist, H. B.(1997) Metallothionein and Fas(CD95) are expressed in squamous cell carcinoma of the tongue. Eur. J. Cancer. 33:1860-1864.
Souza, V., Bucio, L., Gutierrez-Ruiz, M. C. (1997). Cadmium uptake by a human hepatic cell line (WRL-68 cells). Toxicology. 120, 215-220.
Thomas, J. P., Bachowski, G. J., and Girotti, A. W. (1986). Inhibition of cell membrane lipid peroxidation by cadmium metallothioneins and zinc metallothioneins, Biochim. Biophys. Acta. 884, 448-461.
Thornalley, P. J., and Vasak, M. (1985). Possible role for metallothionein in protection against radiation induced oxidative stress - kinetics and mechanism of its reaction with superoxide and hydroxyl radicals, Biochim. Biophys. Acta. 827, 36-44.
Tohyama, H., Yasuda, K. (2002). The effect of increased stress on the patellar tendon. J Bone Joint Surg Br. 84, 440-446.
Tohyama, H., Yasuda, K. (2000). The effects of stress enhancement on the extracellular matrix and fibroblasts in the patellar tendon. J. Biomech. 33, 559-565.
Uchida, Y., Takio, K., Titani, K., Ihara, Y., and Tomonaga, M. (1991). The growth inhibitory factor that is deficient in the Alzheimer’s disease brain is a 68 amino acid metallothionein-like protein. Neuron 7, 337-347.
Viarengo A, Burlando B, Ceratto N, Panfoli I. (2000). Antioxidant role of metallothioneins: a comparative overview. Cell Mol Biol. 46, 407-417.
Vincent, Coulon., Jean, Luc., Veyrune., Nikolai, Tourkine., Annick, Vie., Robert, A., Hipskind., and Jean-Marie, Blanchard. (1999). A novel calcium signaling pathway targets the c-fos intragenic transcriptional pausing site. J. Biol. Chem. 274, 30439-30446.
Waalkes, M. P. (2000). Cadmium carcinogenesis in review. J. Inorg. Biochem. 79, 241-244.
Webb, M. (1979). Functions of hepatic and renal metallothioneins in the
control of the metabolism of cadmium and certain other bivalent
cations. Experientia. suppl. 34, 313-320.
Wei, H. F., Peter, Leeds, Chen, R. W., Wei, W. L., Leng, Y., Dale, E. Bredesen., and Chuang, D. M. (2000). Neuronal apoptosis induced by pharmacological concentrations dantrolene and Bcl-2 overexpression. Journal of Neurochemistry. 75, 81-90.
Westin, G., and Schaffner, W. (1988). A zinc responsive factor interacts with a metal regulated enhancer element (MRE) of the mouse metallothionein-I gene. EMBO J. 7, 3763-3770.
Woo, D., Cederbaum, A. I. (2001). Sodium salicylate increases CYP2E1 levels and enhances arachidonic acid toxicity in HepG2 cells and cultured rat hepatocytes. Molecular Pharmacology. 59, 795-805.
Yagel, M. K., and Palmiter, R.D. (1985). Coordinate regulation of mouse metallothionein-I and Metallothionein-II genes by heavy-metal and glucocorticoids. Mol. Cell. Biol. 5, 291-294.
Yang, C. F., Shen, H. M., and Ong, C. M. (1999). Protective effect of ebselen against hydrogen peroxide-induced cytotoxicity and DNA damage in HepG2 cells. Biochemical Pharmacology. 57, 273-279.
Yang, C. F., Shen, H. M., and Ong, C. M. (2000). Ebselen induces Apoptosis in HepG2 Cells though Rapid Depletion of intracellular thiols. Archives of Biochemistry and biophysics. 374, 142-152.
Yang, J. L., Chao, J. I., and Lin, J. G. (1996). Reactive Oxygen Species May Participate in the Mutagenicity and Mutational Spectrum of Cadmium in Chinese Hamster Ovary-K1 Cells. Chemical Research in Toxicology. 9, 1360-1367.
Yu, C. W., Chen, J. H., and Lin, L. Y. (1997). Metal-induced metallothionein gene expression can be inactivated by protein kinase C inhibitor. FEBS Lett. 420, 69-73.
Zheng, H., Liu, J., Liu, Y. P., and Klaassen, C. D. (1996). Hepatocytes from metallothionein-I and metallothionein-II knock out mice are sensitive to cadmium induced and tert-butylhydroperoxide induced cytotoxicity, Toxicol. Lett. 87, 139-145.
Zhong, Z. J., Troll, W., Koenig, K. L., Frenkel, K. (1990). Carcinogenic sulfide salts of nickel and cadmium induce H2O2 formation by human polymorphonuclear leukocytes. Cancer Research. 50. 7564-7570.

第一頁 上一頁 下一頁 最後一頁 top