Role of elongation factor 2 in regulating peptide-chain elongation in the heart.
Cardiac muscles of experimentally induced diabetic rats show a progressive decrease in the rate of protein synthesis. The decline in protein synthesis is associated with decreases in both the number and efficiency of cardiac ribosomes. In hearts from 48 h diabetic rats, the decrease in protein synthesis was accounted for solely by a 28% reduction in the ribosome content. In contrast, the inhibition of protein synthesis in hearts from 72 h diabetic rats resulted from a reduction in both the ribosome content (28%) and the translational efficiency (30%). The decreased translational efficiency was not associated with an increase of RNA in ribosomal subunits, indicating the defect resulted from an inhibition of peptide-chain elongation/termination. Diabetes of 72 h duration resulted in a 37% inhibition in the rate of peptide-chain elongation. The decreased rate of peptide-chain elongation was associated with a 66% reduction in the amount of elongation factor 2 (EF-2). Treatment of diabetic rats with insulin for 3 days was sufficient to reverse the effects of 72 h diabetes on protein synthesis, RNA content, and translational efficiency. Also, insulin therapy increased the EF-2 content of diabetic rats to control values. These studies suggest that decreased EF-2 content is a molecular mechanism for the impaired rates of peptide-chain elongation in diabetes.
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Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey 17033.
Nairn
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Lynch
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D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010441:Peptide Chain Elongation, Translational / Q000502:physiology*; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors / Q000502:physiology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000037:antagonists & inhibitors; D012313:RNA / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012270:Ribosomes / Q000648:ultrastructure; D013997:Time Factors
D007328:Insulin; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors; D011506:Proteins; D012335:RNA, Ribosomal; D012313:RNA; D003513:Cycloheximide