HYDROGEN-PEROXIDE CYTOTOXICITY IN CULTURED CARDIAC MYOCYTES IS IRON-DEPENDENT
HYDROGEN-PEROXIDE CYTOTOXICITY IN CULTURED CARDIAC MYOCYTES IS IRON-DEPENDENT
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DOI：
10.1152/ajpheart.1994.266.1.h121
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发表时间：
1994-01-01
影响因子：
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通讯作者：
HORWITZ, LD
中科院分区：
文献类型：
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作者：
BYLER, RM;SHERMAN, NA;HORWITZ, LD
由于其在心肌缺血和再灌注损伤中的潜在重要性，我们评估了过氧化氢（H2 O2）在培养的鸡胚心肌细胞中的细胞毒性机制。通过乳酸脱氢酶（LDH）或Cr-51的释放定量损伤，这两者均与台盼蓝拒染法评估的细胞活力丧失相关。铁螯合剂去铁胺（0.25-2 mM），但不是等摩尔的铁负载去铁胺，显着减少LDH和Cr-51的释放。还通过可扩散的活性氧代谢物清除剂二甲基硫脲（10-20 mM）和N-（2-巯基丙酰基）-甘氨酸（20 mM）预防或减轻损伤。羟基自由基清除剂二甲基亚砜（200-400 mM）也可减少损伤。其他清除剂，可能仍然是细胞外，超氧化物歧化酶和甘露醇，是无效的。因此，随着心肌细胞暴露于H2 O2，细胞毒性需要细胞内铁催化的反应。
Because of its potential importance in injury during myocardial ischemia and reperfusion, we assessed mechanisms of hydrogen peroxide (H2O2) cytotoxicity in cultured chick embryo cardiac myocytes. Injury was quantitated by release of lactate dehydrogenase (LDH) or Cr-51, both of which correlated with loss of cell viability assessed by trypan blue exclusion. The iron chelator deferoxamine (0.25-2 mM), but not equimolar iron-loaded deferoxamine, markedly reduced LDH and Cr-51 release. Injury was also prevented or attenuated by the diffusible reactive oxygen metabolite scavengers dimethylthiourea (10-20 mM) and N-(2-mercaptopropionyl)-glycine (20 mM). The hydroxyl radical scavenger, dimethyl sulfoxide (200-400 mM), also reduced injury. Other scavengers that probably remained extracellular, superoxide dismutase and mannitol, were ineffective. Thus, with exposure of cardiac myocytes to H2O2, cytotoxicity requires reactions catalyzed by intracellular iron.