Interaction and Cytotoxic Effect of Superoxide and NO in Reperfusion Injury

超氧化物和 NO 在再灌注损伤中的相互作用和细胞毒性作用

• 批准号: 05670635
• 负责人: NAKAZAWA Hiroe
• 金额: $ 1.34万
• 依托单位: Tokai university school of medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670635/
• 关键词: superoxide; nitric oxide; peroxynitrite; myocyte; cytotoxicity; active oxygen; Reperfusion Injury; NADPHオキシダーゼ

The effects of peroxynitrite (ONOO^-) on cultured cardiac myocytes were examined by simultaneous measurements of intracellular Ca^<2+> ([Ca^<2+>]i) and contractile function. On exposure to 0.2mM ONOO^-, [Ca^<2+>]i increased to beyond the systolic level within 5 min with a concomitant decrease in spontaneous contraction, followed by complete arrest. Addition of a L-type Ca^<2+> channel blocker or removal of extracellular Ca^<2+> prevented the ONOO^--induced increase in [Ca^<2+>]i ; indicating that the increase in [Ca^<2+>]i was caused by the enhanced influx of Ca^<2+> through the plasma membrane and not by the enhanced release from sarcoplasmic reticulum (SR). Plasma membrane fluidity and concentration of the thiobarbiturate acid-reactive substance (TBARS) in the cells remained unchanged by the ONOO^- treatment. The complete cessation of contraction of myocytes persisted even under the massive increase in [Ca^<2+>]i which was induced by an additional saponin (5muM) treatment. In conclusion, ONOO^- increases [Ca^<2+>]i in myocytes through disturbance of Ca^<2+> transport systems in the plasma membrane and impairs contractile protein.

用同步测定心肌细胞内Ca^2+（[Ca^2+]i）和收缩功能的方法，观察了过氧亚硝基阴离子（ONOO^-）对培养心肌细胞的影响。当暴露于0.2mM ONOO^-时，[Ca^2+]i在5分钟内升高至收缩水平以上，同时自发收缩减少，随后完全停止。加入L-型Ca^<2+>通道阻滞剂或去除细胞外Ca^<2+>可阻止ONOO^-诱导的[Ca^<2+]i增加;这表明[Ca^<2+]i的增加是由Ca^<2 +>通过质膜的内流增加引起的，而不是由肌浆网（SR）的释放增加引起的。细胞中硫代巴比妥酸反应物质（TBARS）的质膜流动性和浓度在ONOO^-处理后保持不变。即使在额外的皂苷（5 μ M）处理诱导的[Ca^2+]i大量增加的情况下，肌细胞收缩的完全停止仍然持续。总之，ONOO^-通过干扰质膜Ca^2+转运系统和损害收缩蛋白来增加心肌细胞内[Ca^2+]i。

项目成果

Nakazawa H,Ichimori K,Ishida H,Fukahori M,Umezawa K,Ymashita T: "Cytotoxic effect of superoxide and its interaction with nitric oxide in reperfusion injury, in Feher (eds) : Oxygen Stress and Tissue Damage." Akademiai Kiado, Budapest. 115-129 (1994)

Nakazawa H、Ichimori K、Ishida H、Fukahori M、Umezawa K、Ymashita T：“超氧化物的细胞毒性作用及其在再灌注损伤中与一氧化氮的相互作用，Feher（编辑）：氧应激和组织损伤。”

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