Platelet cytochrome c oxidase activity is an indicator of copper status in rats

Johnson, W. Thomas; Dufault, Steven N.; Thomas, Anne C.

doi:10.1016/s0271-5317(05)80739-0

Cited by 31 publications

(15 citation statements)

References 27 publications

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“…It has been shown that partial inhibition of CCO activity in mitochondria from flight muscle of houseflies increases hydrogen peroxide production (12). This finding indicates that declining CCO activity may contribute to the increase in mitochondrial ROS production that occurs with advancing age~ Suppression of CCO activity in a variety of tissues is also one of the most prominent biochemical changes that occurs during copper deficiency (17)(18)(19). However, it is not known whether the inhibition of CCO activity resulting from copper deficiency is similar to the age-dependent decline in CCO activity in its ability to stimulate mitochondrial ROS production.…”

Section: Introductionmentioning

confidence: 99%

Copper deficiency: A potential model for determining the role of mitochondria in cardiac aging

Johnson

Newman

2003

AGE

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Heart mitochondria experience age-related declines in cytochrome c oxidase (CCO) activity and increases in the generation of reactive oxygen species (ROS) that may contribute to loss of cardiac function and the development of disease that occur with advancing age. In a manner similar to aging, copper deficiency also suppresses heart CCO activity and has cardiovascular consequences related to increased peroxidation. Food restriction is often used as a tool to study oxidative mechanisms of aging and the present study examines the potential of copper deficiency to model the role of mitochondria in cardiac aging by determining if the effect of food restriction on CCO activity and oxidative stress in heart mitochondria parallels its effect on cardiac mitochondria during aging. Overall, copper deficiency severely inhibited CCO activity and increased both Mn superoxide dismutase (MnSOD) and glutathione peroxidase (GPX) in isolated heart mitochondria. However, a 20% reduction in food intake by copper-deficient rats increased CCO activity by 65% and decreased MnSOD activity by 25% but had no effect in rats fed adequate copper. Copper deficiency also reduced the carbonyl content of 80-100 kDa mitochondrial proteins, but the reduction in carbonyl content was unaffected by food restriction. Food restriction did, however, completely prevent the enlargement of cardiac mitochondria in copper-deficient rats. Together, these findings indicate that copper deficiency induces mitochondrial antioxidant enzyme activity and hypertrophy in cardiac tissue in response to reduced CCO activity and that food restriction may counteract these changes by reducing oxidative stress. Because the action of food restriction on CCO activity and mitochondrially generated oxidative stress are similar in copper deficiency and aging, copper deficiency may serve as a short-term model for studying the potential roles of mitochondria in cardiac aging.

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Section: Introductionmentioning

confidence: 99%

Copper deficiency: A potential model for determining the role of mitochondria in cardiac aging

Johnson

Newman

2003

AGE

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“…The lyophilized liver and kidney samples were ashed by using a previously reported method [17] and their Cu concentrations were measured by inductively coupled plasma-emission spectroscopy (Optima 3100 XL, Perkin Elmer, Waltham, MA). The Cu analysis was validated by simultaneous assay of a bovine liver reference sample (No.…”

Section: Methodsmentioning

confidence: 99%

Serum superoxide dismutase 3 (extracellular superoxide dismutase) activity is a sensitive indicator of Cu status in rats

Johnson

Lukaski

2005

The Journal of Nutritional Biochemistry

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“…The rest nuclear-encoded subunits may modulate catalysis, stabilize the catalytic subunits, or assist the assembly of the holoenzyme [15]. COX activity is regulated by Cu and highly sensitive to changes in Cu status [16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Cytochrome c Oxidase is Essential for Copper-Induced Regression of Cardiomyocyte Hypertrophy

et al. 2010

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Previous studies have shown that both copper (Cu) and vascular endothelial growth factor (VEGF) reduce the size of hypertrophic cardiomyocytes, but the Cu-induced regression is VEGF dependent. Studies in vivo have shown that hypertrophic cardiomyopathy is associated with a depression in cytochrome c oxidase (COX) activity, which could be involved in VEGF-mediated cellular function. The present study was undertaken to test the hypothesis that COX is a determinant factor in Cu-induced regression of cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were treated with phenylepherine (PE) at a final concentration of 100 microM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cells were then treated with Cu sulfate at a final concentration of 5 microM in cultures for 24 h with a concomitant presence of PE to examine the effect of Cu on the regression of cardiomyocyte hypertrophy. Cell size changes were determined by flow cytometry, protein content, and molecular markers. Gene silencing was applied to study the effect of COX activity change on the regression of cardiomyocyte hypertrophy. PE treatment decreased COX activity in hypertrophic cardiomyocytes, and Cu addition restored the activity along with the regression of cell hypertrophy. Gene silencing using siRNA targeting COX-I significantly inhibited COX activity and blocked the Cu-induced regression of cell hypertrophy. VEGF alone also restored COX activity; but under the condition of COX inhibition by gene silencing, VEGF-induced regression of cell hypertrophy was suppressed. This study demonstrates that both Cu and VEGF can restore COX activity that is depressed in hypertrophic cardiomyocytes, and COX plays a determinant role in both Cu- and VEGF-induced regression of cardiomyocyte hypertrophy.

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Platelet cytochrome c oxidase activity is an indicator of copper status in rats

Cited by 31 publications

References 27 publications

Copper deficiency: A potential model for determining the role of mitochondria in cardiac aging

Copper deficiency: A potential model for determining the role of mitochondria in cardiac aging

Serum superoxide dismutase 3 (extracellular superoxide dismutase) activity is a sensitive indicator of Cu status in rats

Cytochrome c Oxidase is Essential for Copper-Induced Regression of Cardiomyocyte Hypertrophy

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