| Project/Area Number |
08670174
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Osaka University |
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Principal Investigator |
SUZUKI Keiichiro Osaka University Medical School, Assistant Professor, 医学部, 助手 (70221322)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Junichi Osaka University Medical School, Associate Professor, 医学部, 助教授 (00222258)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | endothelial cells / apoptosis / glutathione / SOD / reactive oxygen species / 抗酸化物質 / NO (peroxynitrite) |
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| Research Abstract |
The Apoptosis of various cells requires inducers including free radicals. Endothelial cells and vascular smooth muscle cells are generally considered to be resistant to apoptosis but recent studies suggest that such changes in these cells relate to atherosclerotic changes. Snake venom generates intracellular peroxides in endothelial cells, which leads to apoptosis. This cell type play an important role in atherosclerosis and its normal resistance to apoptosis may be related to its anti-oxidant levels.
When the intracellular glutathione and Cu, Zn-SOD levels were decreased by the sddition of buthionine sulfoximine (BSO) and diethyldithiocarbamate (DDC), respectively, the apoptosis of endothelial cells was accelerated. The addition of acetylated LDL and glucose enhanced the cytotoxicity of snake venom whereas pretreatment with tumor necrosis factor (TNF) or phorbol ester (TPA), which increases the Mn-SOD level, prevented the apoptosis of endothelialcells. These data suggest that peroxides enhance apoptosis whereas several anti-oxidative agents, such as glutathione and SOD,are protective. The induction of apoptosis by peroxides of endothelial cells may be related to initiation of atheroscrelosis.
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