Mechanism of the inhibition of myocardial protein synthesis during oxygen deprivation.

Abstract

Inhibition of protein synthesis during anoxia in the isolated rabbit right ventricular papillary muscle preparation is totally reversible for up to 2 h if glucose concentration is increased during anoxia. The degree of inhibition of protein synthesis during anoxia is, however, not altered by the presence of increased glucose. Thus inhibition of myocardial protein synthesis induced by anoxia need not be related to irreversible disruption of cellular integrity but may represent metabolic regulation of the synthesis. Tissue content of ATP, ADP, AMP, CP, and lactate and phenylalanine incorporation into protein were measured in individual papillary muscles incubated with varying degrees of O2 deprivation and varying substrates and metabolic inhibitors to determine if the inhibition during anoxia could be ascribed to alterations in tissue high-energy phosphate, adenine nucleotide levels, or rate of metabolic flux through the glycolytic and/or Krebs cycle. Protein synthesis was inhibited in muscles incubated in 15 mM glucose during anoxia despite the fact that in the presence of increased glucose, tissue levels of ATP, ADP, and AMP were equal to that of controls. Protein synthesis was normal in muscles made sufficiently hypoxic so that ATP and CP were significantly decreased and lactate increased. Inhibition of Krebs cycle activity with pentenoate failed to effect the rate of protein synthesis. We conclude that anoxic inhibition of myocardial protein synthesis is due neither to high-energy phosphate depletion nor inhibition of Krebs cycle acitivity. The possibility remains that the inhibition may be related to accumulation of glycolytic intermediates or by-products other than lactate.