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Alcohol-induced oxidative/nitrosative stress alters brain mitochondrial membrane properties

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Abstract

Chronic alcohol consumption causes numerous biochemical and biophysical changes in the central nervous system, in which mitochondria is the primary organelle affected. In the present study, we hypothesized that alcohol alters the mitochondrial membrane properties and leads to mitochondrial dysfunction via mitochondrial reactive oxygen species (mROS) and reactive nitrogen species (RNS). Alcohol-induced hypoxia further enhances these effects. Administration of alcohol to rats significantly increased the mitochondrial lipid peroxidation and protein oxidation with decreased SOD2 mRNA and protein expression was decreased, while nitric oxide (NO) levels and expression of iNOS and nNOS in brain cortex were increased. In addition, alcohol augmented HIF-1α mRNA and protein expression in the brain cortex. Results from this study showed that alcohol administration to rats decreased mitochondrial complex I, III, IV activities, Na+/K+-ATPase activity and cardiolipin content with increased anisotropic value. Cardiolipin regulates numerous enzyme activities, especially those related to oxidative phosphorylation and coupled respiration. In the present study, decreased cardiolipin could be ascribed to ROS/RNS-induced damage. In conclusion, alcohol-induced ROS/RNS is responsible for the altered mitochondrial membrane properties, and alcohol-induced hypoxia further enhance these alterations, which ultimately leads to mitochondrial dysfunction.

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Acknowledgments

The authors thank the Director and staff of the Center for Cellular and Molecular Biology, Hyderabad, India, for providing facilities to carry out fluidity studies. This study was supported in part by the University Grants Commission (Grant No. F-3-11/97), New Delhi, India.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, 515 055, AP, India

    Vaddi Damodara Reddy, Godugu Kavitha, Bulle Saradamma & Nallanchakravarthula Varadacharyulu

  2. Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL, 60637, USA

    Vaddi Damodara Reddy

  3. Section of Hematology/Oncology, Department of Medicine, University of Illinois, Chicago, IL, 60612, USA

    Pannuru Padmavathi

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  1. Vaddi Damodara Reddy
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Correspondence to Nallanchakravarthula Varadacharyulu.

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Reddy, V.D., Padmavathi, P., Kavitha, G. et al. Alcohol-induced oxidative/nitrosative stress alters brain mitochondrial membrane properties. Mol Cell Biochem 375, 39–47 (2013). https://doi.org/10.1007/s11010-012-1526-1

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