Inhibition of protein degradation in the energy-poor heart.
Hypoxia and anoxia were induced in isolated perfused rat hearts by reduction of perfusate oxygen. Ischemia was produced by restricting coronary flow in hearts working against high resistance. Protein degradation, estimated from release of phenylalanine into the perfusate in the presence of cycloheximide, was inhibited in both anoxic and ischemia as compared to aerobic hearts. The effect of ischemia was greater than that of anoxia. A similar inhibitory effect was observed in energy-poor hearts when insulin was present in the perfusate. Other experiments indicated that the effects of energy depletion were exerted at a step early in the degradative pathway, since peptide products of partial proteolysis did not accumulate. A graded reduction in perfusate oxygen tension (hypoxia) led to a significant inhibition of proteolysis with unaltered tissue levels of nucleotides and creatine phosphate. Protein degradation was inhibited in aerobic and anoxic hearts exposed to increasing extracellular levels of hydrogen ions and lactate, suggesting that reduced proteolysis in hearts that are provided limited oxygen may result from accumulation of metabolites as well as from energy depletion per se.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology; D004734:Energy Metabolism; D000860:Hypoxia / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D000596:Amino Acids; D007328:Insulin; D010455:Peptides; D011506:Proteins; D010649:Phenylalanine; D000255:Adenosine Triphosphate; D010100:Oxygen