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Hydrogen peroxide‐induced oxidative stress to the mammalian heart‐muscle cell (cardiomyocyte): Nonperoxidative purine and pyrimidine nucleotide depletion
Author(s) -
Janero David R.,
Hreniuk David,
Sharif Haamid M.
Publication year - 1993
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041550308
Subject(s) - phosphocreatine , oxidative stress , oxidative phosphorylation , purine , biochemistry , adenine nucleotide , chemistry , adenosine triphosphate , hydrogen peroxide , nucleotide , biology , endocrinology , energy metabolism , enzyme , gene
Hydrogen peroxide (H 2 O 2 ) overload may contribute to cardiac ischemia‐reperfusion injury. We report utilization of a previously described cardiomyocyte model (J. Cell. Physiol., 149:347, 1991) to assess the effect of H 2 O 2 ‐induced oxidative stress on heart‐muscle purine and pyrimidine nucleotides and high‐energy phosphates (ATP, phosphocreatine). Oxidative stress induced by bolus H 2 O 2 elicited the loss of cardiomyocyte purine and pyrimidine nucleotides, leading to eventual de‐energization upon total ATP and phosphocreatine depletion. The rate and extent of ATP and phosphocreatine loss were dependent on the degree of oxidative stress within the range of 50 μM to 1.0 mM H 2 O 2 . At the highest H 2 O 2 concentration, 5 min was sufficient to elicit appreciable cardiomyocyte highenergy phosphate loss, the extent of which could be limited by prompt elimination of H 2 O 2 from the culture medium. Only H 2 O 2 dismutation completely prevented ATP loss during H 2 O 2 ‐induced oxidative stress, whereas various freeradical scavengers and metal chelators afforded no significant ATP preservation. Exogenously‐supplied catabolic substrates and glycolytic or tricarboxylic acidcycle intermediates did not ameliorate the observed ATP and phosphocreatine depletion, suggesting that cardiomyocyte de‐energization during H 2 O 2 ‐induced oxidative stress reflected defects in substrate utilization/energy conservation. Compromise of cardiomyocyte nucleotide and phosphocreatine pools during H 2 O 2 ‐induced oxidative stress was completely dissociated from membrane peroxidative damage and maintenance of cell integrity. Cardiomyocyte de‐energization in response to H 2 O 2 overload may constitute a distinct nonperoxidative mode of injury by which cardiomyocyte energy balance could be chronically compromised in the post‐ischemic heart. © 1993 Wiley‐Liss, Inc.