ALPHA-KETOACIDS SCAVENGE H2O2 IN-VITRO AND IN-VIVO AND REDUCE MENADIONE-INDUCED DNA INJURY AND CYTOTOXICITY
ALPHA-KETOACIDS SCAVENGE H2O2 IN-VITRO AND IN-VIVO AND REDUCE MENADIONE-INDUCED DNA INJURY AND CYTOTOXICITY
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DOI：
10.1152/ajpcell.1995.268.1.c227
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发表时间：
1995-01-01
影响因子：
5.5
通讯作者：
NUTTER, LM
中科院分区：
文献类型：
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作者：
NATH, KA;NGO, EO;NUTTER, LM
我们证明，α-酮酸减少，并在某些情况下，消除甲萘醌诱导的DNA损伤和细胞毒性的人乳腺癌细胞系，MCF 7。我们证实，α-酮酸淬灭甲萘醌产生的大量过氧化氢，而这些α-酮酸进行非酶氧化脱羧，因此，我们的数据支持增强过氧化氢的生产作为甲萘醌诱导的DNA损伤和细胞毒性的重要途径。我们还表明，α-酮酸类H2 O2产生的线粒体和微粒体时，这些细胞器暴露于甲萘醌;此外，α-酮酸类保护氧化剂易受损伤的酶对H2 O2诱导的功能障碍。最后，我们提供了第一个在体内的演示，急性升高的α-酮酸在大鼠组织和尿液中的H2 O2的浓度。我们的结论是，增强过氧化氢的产生是甲萘醌诱导的DNA损伤和细胞毒性的主要途径，细胞内存在的各种α-酮酸必须考虑，沿着谷胱甘肽过氧化物酶和过氧化氢酶，作为细胞内抗氧化防御机制的一部分，调节周围的过氧化氢水平。
We demonstrate that alpha-ketoacids reduce and, in some instances, abrogate menadione-induced DNA damage and cytotoxicity in the human breast cancer cell line, MCF7. We confirm that alpha-ketoacids quench the copious amounts of H2O2 generated by menadione while these alpha-ketoacids undergo nonenzymatic oxidative decarboxylation; our data thus support enhanced H2O2 production as an important pathway for menadione-induced DNA damage and cytotoxicity. We also demonstrate that alpha-ketoacids scavenge H2O2 generated by mitochondria and microsomes when these organelles are exposed to menadione; additionally, alpha-ketoacids protect oxidant-vulnerable enzymes against functional impairment induced by H2O2. Finally, we provide the first in vivo demonstration that acute elevations in concentrations of alpha-ketoacids in rat tissues and urine scavenge H2O2. We conclude that enhanced H2O2 production is a major pathway for menadione-induced DNA damage and cytotoxicity and that the diverse alpha-ketoacids present within the cell must be considered, along with glutathione peroxidase and catalase, as part of the intracellular antioxidant defense mechanisms that regulate the ambient levels of H2O2.