Mitochondrial Injury as the Mechanism of Paraquat Toxicity

线粒体损伤是百草枯毒性的机制

• 批准号: 06807124
• 负责人: HIRAI Keiichi
• 金额: $ 1.28万
• 依托单位: Kanazawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06807124/
• 关键词: paraquat; lung injury; mitochondria; free radicals; superoxide; rotenone-insensitive NADH oxidation; herbicide; ミトコンドリア; パラコート中毒; ロテノン非感受性NADHオキシダーゼ; 農薬中毒

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.

一般认为，NADPH-细胞色素c还原酶系统在体外NADPH存在的情况下还原百草枯，因此微粒体组分（对应于内质网）是毒性机制的细胞内位点。相反，我们认为内质网系统可能在百草枯的解毒过程中起作用。百草枯在体内不改变内质网结构，但损伤肺、肝和培养的肺泡II型细胞的线粒体。百草枯和NADH可使离体大鼠肝线粒体肿胀和破坏，SOD、细胞色素C或对苯醌可保护线粒体。电子细胞化学技术被用来证明百草枯依赖的自由基产生网站的亚细胞位置。超氧化物或过氧化氢的产生仅限于线粒体外膜，并受到过氧化氢酶、细胞色素c、SOD和对苯醌的抑制。经DEAE柱层析、凝胶过滤和CM柱层析，从大鼠肝线粒体中分离出代表52 kD单多肽的“NADH-百草枯还原酶”。该肽对鱼藤酮不敏感，在百草枯和NADH存在下产生超氧阴离子。

项目成果

平井圭一: "身体とそのしくみ(酸素とのお付き合い):老化からガンまで" 石川自治と教育. 484. 36-49 (1994)

Keiichi Hirai：“身体及其机制（与氧气的关系）：从衰老到癌症”石川治一教育。 484. 36-49 (1994)

平井圭一: "組織学・組織化学的アプローチ" 朝倉書店, 310 (1996)

平井敬一：“组织学/组织化学方法”朝仓书店，310（1996）

平井圭一: "パラコート急性中毒の機構" 金医大誌. 20(発表予定). (1996)

Keiichi Hirai：“急性百草枯中毒的机制”Jin医科大学学报20（待出版）。

Kei-Ichi Hirai: The World of Human Body.Huujinsha Co, Ltd., Tokyo.,

Kei-Ichi Hirai：人体的世界。Huujinsha Co., Ltd.，东京。

Kei-Ichi Hirai: Histology.Histochemical Approaches.Asakura-Shoten Inc., Tokyo,

Kei-Ichi Hirai：组织学。组织化学方法。Asakura-Shoten Inc.，东京，