Acute alterations in sodium flux in vitro lead to decreased myofibrillar protein breakdown in rat skeletal muscle.
Myofibrillar protein breakdown was evaluated by measuring the release of N tau-methylhistidine by isolated rat skeletal muscles or perfused rat muscles in the presence of a variety of agents known to affect Na+ flux. Total cell proteolysis was evaluated simultaneously by measuring tyrosine release by muscles after the inhibition of protein synthesis with cycloheximide. Treatment of muscles with the Na+ ionophore monensin or inhibitors of Na+-K+ ATPase (ouabain, digoxin or vanadate) decreased N tau-methylhistidine release by muscles by 21-35%. A phorbol ester (phorbol 12-myristate 13-acetate) as well as a synthetic diacylglycerol known to activate protein kinase C and a Na+/H+ antiport also decreased N tau-methylhistidine release by muscles. Removal of extracellular Na+ blocked the ability of these agents to attenuate N tau-methylhistidine release by muscles, suggesting that their effectiveness required a change in Na+ flux. In contrast with N tau-methylhistidine release by muscles, these agents, except for monensin, did not effect the release of tyrosine, suggesting that they attenuate specifically the breakdown of myofibrillar proteins. Overall these results indicate a link between Na+ and the regulation of protein breakdown in rat skeletal muscle, whereby an influx of Na+ can result in a decrease in myofibrillar proteolysis. Left unresolved is whether phospholipid hydrolysis is involved in this scheme.
Goodman
M N
MN
Department of Medicine, University of California at Davis, Sacramento 95817.
D000818:Animals; D004075:Diglycerides / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology; D008297:Male; D008762:Methylhistidines / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects; D009210:Myofibrils / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
D004075:Diglycerides; D008762:Methylhistidines; D009124:Muscle Proteins; D010455:Peptides; D014638:Vanadates; D010042:Ouabain; D004077:Digoxin; C038237:1-oleoyl-2-acetylglycerol; D008985:Monensin; D012964:Sodium; C028118:3-methylhistidine; D013755:Tetradecanoylphorbol Acetate