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Effect of chronic heart failure on mitochondrial function and apoptotic susceptibility in rat skeletal muscle
Author(s) -
Nguyen Linda M.D.,
CareyLove Sean D.,
Ahn Bumsoo,
Ferreira Leonardo F.,
Adhihetty Peter J.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1209.19
Subject(s) - mitochondrion , skeletal muscle , apoptosis , heart failure , cytochrome c , medicine , respiration , endocrinology , oxidative phosphorylation , reactive oxygen species , oxidative stress , biology , microbiology and biotechnology , biochemistry , anatomy
Chronic heart failure (CHF) is marked by myocardial dysfunction and is also associated with skeletal muscle metabolic abnormalities but the underlying cellular mechanisms are not well understood. Thus, we investigated whether CHF alters mitochondrial function/content and apoptotic susceptibility in skeletal muscle. Young Lewis rats (8 wks) were subjected to either myocardial infarction to induce CHF or, Sham (Sh) operation, and hindlimb muscles were removed 16‐weeks post‐surgery (n=6/group). Mitochondrial function tended to be impaired in CHF as indicated by a reduced respiratory control ratio (RCR‐State 3/4 respiration). CHF‐induced impairments in respiration coincided with significant reductions in cytochrome c and the mitochondrial anti‐oxidant, MnSOD, in isolated mitochondria. Additionally, oxidative damage, indicated by protein carbonylation was significantly elevated in CHF. CHF animals tended to exhibit greater mitochondrial apoptotic susceptibility (Bax:Bcl‐2) but this surprisingly did not alter the vulnerability to exogenous H2O2‐ induced pro‐apoptotic release from isolated mitochondria. Our preliminary results indicate CHF impairs mitochondrial function and/or content, increases mitochondrial apoptotic susceptibility and enhances ROS‐induced damage in muscle, and these deleterious mitochondrial‐associated adaptations likely contribute towards CHF pathogenesis.