Pyruvate prevents hydrogen peroxide-induced apoptosis.
Studies were carried out to investigate the protective effects of pyruvate, a key glycolytic intermediate and alpha-keto-monocarboxylate, against oxidative stress-induced apoptosis. Oxidative stress was induced by treating mouse thymocytes with 25 microM hydrogen peroxide for 15 min at 37 degrees C under 5% CO2 in air. Pre- and post-treatment of cells with 10 mM pyruvate inhibited morphological changes, internucleosomal DNA fragmentation, and translocation of phosphatidylserine to the plasma membrane surface, which are characteristic features of apoptosis. L-lactate (10 mM) and acetate (10 mM) were ineffective in inhibiting apoptosis and appeared to be toxic to the cells under similar conditions. The results suggest that pyruvate has therapeutic potential for use in the treatment of oxidative stress-induced disorders associated with increased apoptosis.
Ramakrishnan
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Department of Applied Cellular Radiobiology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5603, USA. Rama@mx.afrri.usuhs.mil
Chen
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McClain
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DE
Bünger
R
R
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019344:Lactic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D011419:Propidium; D019289:Pyruvic Acid / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland
D000085:Acetates; D017304:Annexin A5; D010718:Phosphatidylserines; D019344:Lactic Acid; D011419:Propidium; D019289:Pyruvic Acid; D006861:Hydrogen Peroxide