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Glucocorticoid effects on oxidative stress and mitochondrial dysfunction Tang, Victor Mark


Background: Many major psychiatric illnesses have been associated with aberrant stress response systems. In particular, those with mood disorders have been found to have an excessive and prolonged release of glucocorticoid stress hormones. Studies have also begun to reveal increased oxidative damage through mitochondrial dysfunction as part of the pathophysiology of such disorders. As both behaviorally induced stress and glucocorticoid treatment can increase the production of reactive oxygen species, this study aims to look at the effects of glucocorticoids on protein oxidative damage, mitochondrial function, and antioxidant activity. Methods: The effects of chronic treatment with corticosterone on cultured rat PC12 cells were examined. Protein oxidative damage was measured using both a spectrophotometric and immunoblotting method for protein carbonylation. Activity of the mitochondrial electron transport chain protein was examined through spectrophotometric techniques that measured complex I by quantifying NADH oxidation and complex III by cytochrome C reduction. Total antioxidant capacity (TAC) was measured to assess intracellular antioxidant capacity using a spectrophotometric assay. Results: It was found that chronic treatment with corticosterone was able to increase the amount of protein carbonylation in PC12 cells. Complex I activity, but not complex III, was decreased with drug treatment. TAC did not show any significant differences at doses which affected carbonylation or complex I activity. Limitations: The effects found with the time course and dosage of glucocorticoid treatment used here in cultured cells may be different then those found in normal or pathophysiological human conditions. Further research should also determine whether there are significant effects on neuronal function. Conclusions: Excessive glucocorticoid activity can decrease mitochondrial activity, leading to oxidative damage. Thus, over-active stress response systems and oxidative stress may be interrelated in the neurobiology of mood disorders, and may underlie neuronal pathophysiology in associated diseases. Moreover, chronic psychological stress could lead to detrimental effects on the brain through protein oxidation and mitochondrial dysfunction. Elucidation of these processes may open new possibilities for psychiatric treatments.

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