| Project/Area Number |
63440025
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
TAGAWA Kunio Osaka Univ., Physiol. Chem., Prof., 医学部, 教授 (40028296)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIIKE Wataru Osaka Univ., Surgery, Assist., 医学部, 助手 (40152847)
KAZUHEI Kurosawa Osaka Univ., Physiol. Chem., Assist., 医学部, 助手 (70178127)
YOSHIDA Yukuo Osaka Univ., Physiol. Chem., Assoc. Prof., 医学部, 助教授 (10144453)
古谷 榮助 大阪大学, 医学部, 助教授 (00028523)
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| Project Period (FY) |
1988 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥31,400,000 (Direct Cost: ¥31,400,000)
Fiscal Year 1991: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1990: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1989: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1988: ¥20,400,000 (Direct Cost: ¥20,400,000)
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| Keywords | calcium / ischemia / anoxia / cytoskelton / reoxygenation / cyclosporin A / mitochondria / bleb / 虚血 / 細胞内カルシウム / 潅流 / 再潅流障害 / グルタチオン / Indo 1 / 灌流 / 再灌流障害 / Bleb / 細胞骨格系 / 過酸化障害 |
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| Research Abstract |
In an attempt to clarify the process of ischemic or anoxic injury, we studied mechanisms involved in the dysfunction of mitochondria and disruption of cytoskelton system during anoxia, making focus on the homeostasis and variation in the intracellular level of calcium.
Results obtained from the prigment study are as follows : (1) The leakage of cytosolic enzymes from anoxic heart or liver is due to disruption of blebs which have been formed during anoxia by mechanical stress of blood flow or contraction of muscles. (2) Application of a newly-developed spectrofluorophotometer combined with fiber to the perfused heart enabled to make a real-time measurement of variation of intracellular calcium in response to muscle contraction, and to directly observe changes in the calcium level during anoxia and reoxygenation. (3) In the perfused liver and heart, matrix enzymes were leaked out during reoxygenation, mechanism of which was considered to be different from that of leakage of cytosolic enzymes. (4) Reoxygenation of isolated mitochondria caused leakage of matrix'enzymes, simultaneously with the generation of hydrogen peroxide. This was not due to activation of phospholipase A2, but was a calcium-dependent phenomenon which is strongly inhibited by ATP or cyclosporin A. This non-specific increase in permeability of the inner membrane was considered to be the main cause of reoxygenation injury of mitochondria.
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