2000 Fiscal Year Final Research Report Summary
Reactive oxygen species induced apoptosis in ischemia-reperfusion injury
| Project/Area Number |
11470322
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
ARAI Toshiyuki Kyoto University, Medicine, Associated Professor, 医学研究科, 助教授 (80175950)
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| Co-Investigator(Kenkyū-buntansha) |
SASADA Masataka Kyoto University, College of Medical Technology, Professor, 医療技術短期大学部, 教授 (30144364)
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| Project Period (FY) |
1999 – 2000
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| Keywords | 6-formylpterin / geranylgeranylacetone / propofol / peroxynitrite / iNOS / thioredoxin / ROS / apoptosis |
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| Research Abstract |
Effects of 6-formylpterin (6FP), geranylgeranylacetone (GGA) and propofol on the production of reactive oxygen species (ROS) and ischemia-reperfusion injury were investigated using electron paramagnetic resonance (EPR) and flow cytometry.
1) Effects of 6FP on the production of nitrotyrosine as a footprint of tyrosine nitration by peroxynitite, a strong oxidant, were examined. The results showed that 6FP was not necessarily a strong scavenger of peroxynitite.
2) Effects of 6FP on the production of nitric oxide (NO) in macrophages were examined. The results showed that 6FP suppressed both iNOS induction and NOS activity, which resulted in the inhibition of NO production.
3) Effects of GGA on ethanol-induced cytotoxicity in rat hepatocytes were examined. The results showed that GGA facilitated the induction of thioredoxin, an antioxidant, which exerted the cytoprotective effects on the hepatocytes.
4) The chemical property of 6FP and its biological functions were examined. The results showed that 6FP reacted with reducing agents, such as NAD(P)H, and generated ROS, which induced apoptosis, suppression of cell proliferation and inhibition of Fas-induced apoptosis.
5) Effects of propofol on neuronal damage in focal cerebral ischemia in hyperglycemic rats were examined. The results showed that ppropofol suppressed lactate accumulation and edema formation in brain, which resulted in the attenuation of the neuronal damage.
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[Publications] Arai T, Endo N, Yamashita K, Sasada M, Mori H, Ishii H, Hirota K, Makino K, Fukuda K: "6-formylpterin, a xanthine oxidase inhibitor, intracellularly generates reactive oxygen species involved in apoptosis and cell proliferation."Free Radic Biol Med. 30. 248-259 (2001)
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