Tzeng W F, Lee J L, Chiou T J
Department of Biology, Fu Jen University, Taipei, Taiwan, Republic of China.
J Mol Cell Cardiol. 1995 Sep;27(9):1999-2008. doi: 10.1016/0022-2828(95)90021-7.
The role of lipid peroxidation in menadione-mediated toxicity was studied in neonatal rat cardiomyocytes. Incubation of cardiomyocytes with menadione resulted in depleted cellular glutathione levels, increased intracellular Ca2+ and increased lipid peroxidation which all occurred prior to cell degeneration. Pre-treatment of cells with cysteine suppressed the menadione-induced cell degeneration and prevented changes in glutathione levels, intracellular Ca2+, and lipid peroxidation. Pre-treatment of cells with fura-2 acetoxymethyl ester, a Ca2+ chelator, reduced menadione-induced cell degeneration and lipid peroxidation but it did not block cellular glutathione depletion. Pre-treatment of cells with deferoxamine mesylate, an iron chelator, also reduced both menadione-induced cell degeneration and lipid peroxidation; however, it did not prevent the menadione-induced increase in intracellular Ca2+, nor the depletion of glutathione. Thus, the inhibition of menadione-induced lipid peroxidation by deferoxamine mesylate prevented cell degeneration even though intracellular Ca2+ remained elevated and glutathione remained depleted. The protective effects of deferoxamine mesylate and fura-2 AM on menadione's toxicity were inhibited by addition of FeCl3 to cells. Ferric ions did not inhibit the protective effect of cysteine. These data suggest that menadione-induced cardiomyocyte degeneration is directly linked to iron-dependent lipid peroxidation and less tightly coupled to elevation in intracellular Ca2+ or depletion of glutathione.
在新生大鼠心肌细胞中研究了脂质过氧化在甲萘醌介导的毒性中的作用。用甲萘醌孵育心肌细胞导致细胞内谷胱甘肽水平降低、细胞内钙离子增加以及脂质过氧化增加，所有这些都发生在细胞变性之前。用半胱氨酸预处理细胞可抑制甲萘醌诱导的细胞变性，并防止谷胱甘肽水平、细胞内钙离子和脂质过氧化的变化。用钙离子螯合剂fura-2乙酰氧甲酯预处理细胞可减少甲萘醌诱导的细胞变性和脂质过氧化，但它不能阻止细胞内谷胱甘肽的消耗。用铁螯合剂甲磺酸去铁胺预处理细胞也可减少甲萘醌诱导的细胞变性和脂质过氧化；然而，它不能阻止甲萘醌诱导的细胞内钙离子增加，也不能阻止谷胱甘肽的消耗。因此，即使细胞内钙离子仍然升高且谷胱甘肽仍然消耗，甲磺酸去铁胺对甲萘醌诱导的脂质过氧化的抑制作用仍可防止细胞变性。向细胞中添加氯化铁可抑制甲磺酸去铁胺和fura-2 AM对甲萘醌毒性的保护作用。铁离子不抑制半胱氨酸的保护作用。这些数据表明，甲萘醌诱导的心肌细胞变性与铁依赖性脂质过氧化直接相关，而与细胞内钙离子升高或谷胱甘肽消耗的关联较小。
