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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #131355
Title: OXIDATIVE STRESS RESULTING FROM INHIBITION OF THE MITOCHONDRIAL ELECTRON TRANSPORT CHAIN CONTRIBUTES TO THE INDUCTION OF HEPATIC HEME OXYGENASE-1 INCOPPER-DEFICIENT RATS

Author
item Johnson, William

Submitted to: Trace Elements in Man and Animals International Symposium
Publication Type: Abstract Only
Publication Acceptance Date: 6/2/2002
Publication Date: 5/1/2003
Citation: Johnson, W.T. 2003. Oxidative stress resulting from inhibition of the mitochondrial electron transport chain contributes to the induction of hepatic heme oxygenase-1 in copper deficient rats [abstract]. Journal of Nutrition. 133(5S-1):203E.

Interpretive Summary:

Technical Abstract: One goal of this study was to determine whether the increase in HO activity caused by Cu deficiency reflects an increase in the expression of HO-1, which is an inducible form of HO, or an increase in P450Red. A second goal was to determine if mitochondrial stress contributes to the induction of heme oxygenase by Cu deficiency. Weanling rats were fed either Cu-deficient t(0.3 mg Cu/kg) or Cu-adequate (5.4 mg Cu/kg) diets for 5 weeks. Optical density units obtained from scanning densitometry (mean+/-SEM) were 4.59+/- 0.17 and 2.66+/-0.34 for HO-1 (P<0.05, one-tail t-test) and 1.11+/-0.08 and 0.99+/-0.15 for P450R (P>0.05) in Cu-deficient (N=10) and control rats (N=9), respectively. This finding indicates that Cu deficiency increases HO-1 but has no effect on P450R and that induction of HO-1 is a likely explanation for increased hepatic HO activity caused by Cu deficiency. Activities of mitochondrial NADH:cytochrome c reductase (NADHCytR), succinate:cytochrome c reductase (SucCytR), and cytochrome c oxidase (CCO) were inhibited 70%, 41% and 31% (P<0.05), respectively, in Cu-deficient rats. In addition, HO-1 content in Cu-deficient rats was inversely correlated with NADHCytR (R**2=0.6, P<0.05). HO-1 content also exhibited negative exponential associations (P<0.001) with CCO activity and NADHCytR activity across both dietary groups. A mechanism for HO-1 induction during Cu deficiency may involve increased mitochondrial oxidative stress resulting from decreased cytochrome c oxidase and respiratory complex I activities. In the present study, rates of hydrogen peroxide production (mean+/-SEM) by isolated hepatic mitochondria in the presence of 10mM glutamate were 1.25+/-0.18 and 0.84+/-0.11 pmol/(sec x mg protein) (P<0.05) for Cu-deficient and control rats, respectively.