title: Alcohol-induced oxidative/nitrosative stress alters brain mitochondrial membrane properties.
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.
authors.affiliation: Department of Biochemistry, Sri Krishnadevaraya University, Anantapur 515 055, AP, India.
authors.forename: Vaddi Damodara
authors.initials: VD
authors.lastname: Reddy
authors.forename: Pannuru
authors.initials: P
authors.lastname: Padmavathi
authors.forename: Godugu
authors.initials: G
authors.lastname: Kavitha
authors.forename: Bulle
authors.initials: B
authors.lastname: Saradamma
authors.forename: Nallanchakravarthula
authors.initials: N
authors.lastname: Varadacharyulu
mesh_terms: D000818:Animals; D016880:Anisotropy; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000201:enzymology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D045222:Electron Transport Chain Complex Proteins; D000431:Ethanol; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009566:Nitrates; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites; D000254:Sodium-Potassium-Exchanging ATPase; D013482:Superoxide Dismutase; D017392:Thiobarbituric Acid Reactive Substances; D000099156:Superoxide Dismutase 2; C497444:Hif1a protein, rat; C496318:Nos2 protein, rat