| 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)
MANN Giovann ロンドン大学, キングスカレッジ, 教授
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | oxidative stress / stress protein / macrophages / vascular smooth muscle cell / amino acid transporter / heme oxygenase / glutathione / atherosclerosis / アミノ酸トシンスポーター / ストレス タンパク質 / 一酸化窒素 / 定密度リポタンパク |
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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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