1995 Fiscal Year Final Research Report Summary
Mitochondrial Injury as the Mechanism of Paraquat Toxicity
| Project/Area Number |
06807124
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
HIRAI Keiichi Kanazawa Medical University, Anatomy, Professor, 医学部, 教授 (60027092)
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| Co-Investigator(Kenkyū-buntansha) |
SIMAMURA Eriko Kanazawa Medical University, Anatomy, Assistant, 医学部, 助手 (00267741)
SIMADA Hiroki Kanazawa Medical University, Anatomy, Assistant, 医学部, 助手 (60278108)
AONO Makoto Kanazawa Medical University, Anesthesiology, Professor, 医学部, 教授 (10014218)
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| Project Period (FY) |
1994 – 1995
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| Keywords | paraquat / lung injury / mitochondria / free radicals / superoxide / rotenone-insensitive NADH oxidation / herbicide |
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| Research Abstract |
In has generally been believed that NADPH-cytochrome c reductase systems reduce paraquat in the presence of NADPH in vitro, and therefore the microsomal fractions (correponding to the endoplasmic reticulum) are the intracellular site of the toxic mechanism. Contraversely, we deonstrated that the endoplasmic reticular systems may play a role in the detoxication of paraquat. Paraquat did not alter the endoplasmic reticulum structure in vivo but damaged mitochondria alone of the lung and liver, and of cultured alveolar type II cells.
Isolated rat liver mitochodnria were swollen and destructed in the presence of paraquat and NADH,and protected by SOD,cytochorme c or p-benzoquinone. Electron-cytochemical techniques were used to demonstrate the subcellular location of paraquat-dependent free radical production sites. The production of superoxide or hydrogen peroxide was restricted to the outer mitochondrial membrane and inhibited by catalase, cytochrome c, SOD and p-benzoquinone.
"NADH-paraquat reductase" repesenting 52 kD single polypeptide was ioslated from the rat liver mitochndoria through DEAE chromatography, gel filtration and CM chromatography. This peptide was insensitive to rotenone and produced superoxide anions in the presence of paraquat and NADH.
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