Increased heme oxygenase-1 expression during copper deficiency in rats results from increased mitochondrial generation of hydrogen peroxide1-4

被引:20
|
作者
Johnson, WT [1 ]
DeMars, LCS [1 ]
机构
[1] USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA
来源
JOURNAL OF NUTRITION | 2004年 / 134卷 / 06期
关键词
heme oxygenase; mitochondria; hydrogen peroxide; respiratory complexes; copper deficiency;
D O I
10.1093/jn/134.6.1328
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
The activity of hepatic heme oxygenase (HO) in rats is elevated in response to copper deficiency. However, the mechanism responsible for the increase in HO activity is; poorly understood. Oxidative stress is a common denominator for many of the signals that induce HO-1, the inducible isoform of HO. The present study evaluated the role of H2O2 and the mitochondrial electron transport chain as a potential mechanism for the induction of HO-1 during copper deficiency. Mitochondria isolated from the livers of young male rats fed a copper-deficient diet for 5 wk had significantly (P < 0.05) reduced levels of NADH:cytochrome c reductase (31% reduction), succinate:cytrochrome c reductase (42% reduction), and cytochrome c oxidase (70% reduction) activities and significantly increased production of H2O2 (48% increase) when glutamate was used as a substrate. Hepatic levels of HO-1 protein and mRNA were also significantly elevated (48 and 20%, respectively) in copper-deficient rats, indicating that copper deficiency stimulated the expression of the HO-1 gene. Furthermore, hepatic HO-1 protein content was best described by a regression model that included mitochondrial NADH:cytochrome c reductase and succinate:cytochrome c reductase activities, but not cytochrome c oxidase activity (R-2 = 0.54, P < 0.02). Hydrogen peroxide is a known inducer of HO-1, and our results suggest that increased mitochondrial H2O2 production resulting from inhibition of respiratory complex activities contributes to the induction of HO-1 during copper deficiency. The levels of HO-1 protein and mRNA were also elevated (85 and 95%, respectively) in hearts from copper-deficient rats, indicating that the effects of copper deficiency on HO-1 gene expression are not limited to hepatic tissue.
引用
收藏
页码:1328 / 1333
页数:6
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