Mechanism of peroxide-induced cellular injury in cultured adult cardiac myocytes
- Oregon Health Sciences Univ., Portland (United States)
Cultured adult rat cardiomyocytes were incubated with physiological concentrations of peroxide. The cellular extract and incubation medium were analyzed for adenine nucleotides and purines by reverse-phase high-pressure liquid chromatography. Cellular glutathione efflux was determined by enzymatic analysis of the incubation medium. Pyruvate dehydrogenase (PDH) activity was determined in the cultured myocytes as well as in freshly isolated cardiac mitochondria using (1-C{sup 14}) pyruvate. Extracellular glutathione rose 3.3-fold in response to small doses of peroxide. Likewise, small quantities of peroxide reduced total cellular adenine nucleotides to 50-60% of control values with only a modest reduction in energy charge. Peroxide-treated myocytes selectively release inosine and adenosine, as only these two purine degradation products were detected in the incubation medium. The most dramatic response was a peroxide dose-dependent inhibition of PDH activity in cultured myocytes as well as freshly isolated mitochondria; just 65 and 30 nmol peroxide/mg protein induced a 50% reduction in cellular and mitochondrial PDH activity, respectively. In conclusion, physiological quantities of peroxide potently inhibit PDH in cultured cardiomyocytes and isolated cardiac mitochondria. PDH inhibition blocks the aerobic oxidation of glucose and inhibits the oxidative phosphorylation of ADP, which in turn lead to cellular adenine nucleotide degradation.
- OSTI ID:
- 5886072
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Vol. 5:11; ISSN FAJOE; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALDEHYDES
ANIMAL CELLS
ANIMALS
ATP
BODY
CARBOHYDRATES
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CELL CULTURES
CHEMICAL REACTIONS
GLUCOSE
HEART
HEXOSES
INHIBITION
KETO ACIDS
MAMMALS
METABOLISM
MITOCHONDRIA
MONOSACCHARIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDATION
OXYGEN COMPOUNDS
PEROXIDES
PHOSPHORYLATION
PYRUVIC ACID
RATS
RODENTS
SACCHARIDES
TOXICITY
VERTEBRATES