TAILIEUCHUNG - Báo cáo khoa học: Adaptive changes in the expression of nuclear and mitochondrial encoded subunits of cytochrome c oxidase and the catalytic activity during hypoxia

The effects of physiologically relevant hypoxia on the catalytic activity of cytochromecoxidase (CytOX), mito-chondrial gene expression, and both nuclear and mito-chondrial encoded CytOX mRNA levels were investigated in murine monocyte macrophages, mouse C2C12 skeletal myocytes and rat adrenal pheochromocytoma PC12 cells. Our results suggest a coordinated down regulation of mito-chondrial genome-coded CytOX I and II and nuclear genome-codedCytOX IV andVbmRNAs during hypoxia. | Eur. J. Biochem. 270 871-879 2003 FEBS 2003 doi Adaptive changes in the expression of nuclear and mitochondrial encoded subunits of cytochrome c oxidase and the catalytic activity during hypoxia C. Vijayasarathy1 t Shirish Damle1 Subbuswamy K. Prabu1 Cynthia M. Otto2 and Narayan G. Avadhani1 1 Department of Animal Biology and department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Philadelphia PA USA The effects of physiologically relevant hypoxia on the catalytic activity of cytochrome c oxidase CytOX mitochondrial gene expression and both nuclear and mitochondrial encoded CytOX mRNA levels were investigated in murine monocyte macrophages mouse C2C12 skeletal myocytes and rat adrenal pheochromocytoma PC12 cells. Our results suggest a coordinated down regulation of mitochondrial genome-coded CytOX I and II and nuclear genome-coded CytOX IV and Vb mRNAs during hypoxia. Hypoxia also caused a severe decrease in mitochondrial transcription rates and associated decrease in mitochondrial transcription factor A. The enzyme from hypoxia exposed cells exhibited altered subunit content as revealed by blue native gel electrophoresis. There was a generalized decline in mitochondrial function that led to a decrease in total cellular heme and ATP pools. We also observed a decrease in mitochondrial heme aa3 content and decreased levels of CytOX subunit I IV and Vb though the catalytic efficiency of the enzyme TN for cytochrome c oxidase remained nearly the same. Increased glycolytic flux and alterations in the kinetic characteristics of the CytOX might be the two mechanisms by which hypoxic cells maintain adequate ATP levels to sustain life processes. Reoxygenation nearly completely reversed hypoxia-mediated changes in CytOX mRNA contents rate of mitochondrial transcription and the catalytic activity of CytOX enzyme. Our results show adaptive changes in CytOX structure and activity during physiological hypoxia. .

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