2000 Fiscal Year Final Research Report Summary
Response of Vascular Cells to Oxidative Stress
| Project/Area Number |
10044234
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
BANNAI Shiro University of Tsukuba, Institute of Basic Medical Sciences, Professor, 基礎医学系, 教授 (70019579)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Hideyo University of Tsukuba, Institute of Basic Medical Sciences, Lecturer, 基礎医学系, 講師 (60235380)
ISHII Tetsuro University of Tsukuba, Institute of Basic Medical Sciences, Associate Professor, 基礎医学系, 助教授 (20111370)
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| Project Period (FY) |
1998 – 2000
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| Keywords | oxidative stress / stress protein / macrophages / vascular smooth muscle cell / amino acid transporter / heme oxygenase / glutathione / atherosclerosis |
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| Research Abstract |
We have investigated the response to oxidative stress in vascular cells and tissues.
The results are as follows :
1. Macrophages are thought to be able to oxidize low-density lipoprotein (LDL).Oxidation of LDL is probably coupled with reduction of ferric ion. We have obtained evidence showing that activated macrophages can reduce ferric ion though resting macrophages cannot.
2. We have examined the effects of oxidized LDL and the antioxidant vitamin C in human arterial smooth muscle cells. These cells exhibit typical response to oxidized LDL but pretreatment with vitamin C abolishes the response in a dosedependent manner.
3. We have obtained evidence showing the high expression of heme oxygenase 1 in atherosclerotic region, particularly in macrophages.
4. cDNA for cystine/glutamate transporter has been cloned. Two proteins, 4F2hc and xCT, constitute the transporter. xCT is a novel protein with 12 transmembrane domains. The activity of the transporter is important in maintaining intracellular glutathione level and hence in tolerance to oxidative stress. The 5'-flanking region of xCT gene has been analyzed and the regulation of the transcription by the transcription factor Nrf2 has been found.
5. Induction of peroxiredoxin I by oxidative stress has been examined and the transcriptional regulation similar to that of cystine transporter protein xCT has been found.
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[Publications] Tachi, Y., Okuda, Y., Bannai, C., Okamura, N., Bannai, S.and Yamashita, K.: "High concentration of glucose causes impairment of the function of the glutathione redox cycle in huamn vascular smooth muscle cells."FEBS Lett.. 421. 19-22 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Siow, R.C.M., Sato, H., Leake, D.S., Pearson, J.D., Bannai, S., and Mann, G.E.: "Vitamin C Protects Human Arterial Smooth Muscle Cells Against Atherogenic Lipoproteins"Arterioscler Thromb Vasc Biol.. 18. 1662-1670 (1998)
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[Publications] Ishii, T., Itoh, K., Takahashi, S., Sato, H., Yanagawa, T., Katoh, Y., Bannai, S., and Yamamoto, M.: "Transcription factor Nrf-2 coordinately regulates a group of oxidative stress-inducible genes in macrophages."J.Biol.Chem.. 275. 16023-16029 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Hong, Y., Suzuki, S., Yatoh, S., Mizutani, M., Nakajima, T., Bannai, S., Sato, H., Soma, M., Okuda, Y., and Yamada, N.: "Effect of hypoxia on nitric oxide production and its synthase gene expression in rat smooth muscle cells."Biochem.Biophys.Res.Commun.. 268. 329-332 (2000)
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[Publications] Sato, H., Tamba, M., Kuriyama-Matsumura, K., Okuno, S., and Bannai, S.: "Molecular cloning and expression of human xCT, the light chain of amino acid transport system xc-."Antioxi.Redox Signal.. 2. 665-671 (2000)
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[Publications] Sato, H., Kuriyama-Matsumura, K., Hashimoto, T., Sasaki, H., Wang, H., Ishii, T., Mann, G.E., and Bannai, S.: "Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages."J.Biol.Chem.. 276. 10407-10412 (2001)
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