Manganese superoxide dismutase protects mitochondrial complex I against adriamycin-induced cardiomyopathy in transgenic mice

被引:116
作者
Yen, HC
Oberley, TD
Gairola, CG
Szweda, LI
St Clair, DK
机构
[1] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA
[2] Univ Kentucky, Tobacco & Hlth Res Inst, Lexington, KY 40536 USA
[3] Univ Wisconsin, Vet Adm Hosp, Dept Pathol & Lab Med, Madison, WI 53705 USA
[4] Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA
关键词
MnSOD; adriamycin; mitochondria; heart;
D O I
10.1006/abbi.1998.1011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Adriamycin (ADR) is a potent anticancer drug that causes severe cardiomyopathy, We have previously demonstrated that ADR-induced ultrastructural mitochondrial injury in the heart was attenuated in manganese superoxide dismutase (MnSOD) transgenic mice. To further investigate the biochemical mechanisms by which MnSOD protected mitochondria against ADR-induced damage, cardiac mitochondrial function and activities were evaluated, The results showed that ADR caused significant decrease in state 3 respiration and respiratory control ratio using both complex I and II substrates in nontransgenic mice. In transgenic mice, state 3 respiration for complex I substrates remained unaffected by ADR, but was reduced for complex II substrate. Complex I activity was significantly decreased in nontransgenic, but not in transgenic mice after ADR treatment, suggesting that mitochondrial complex I is sensitive to inactivation by superoxide radicals. The activities of complex II and mitochondrial creatine kinase were decreased by ADR in both nontransgenic and transgenic mice. These results support our previous observations on the protective role of MnSOD on the ultrastructural damage of the heart after ADR treatment and extend the understanding of its mechanisms in mitochondria. (C) 1999 Academic Press.
引用
收藏
页码:59 / 66
页数:8
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