Influence of calcium and other divalent cations on protein turnover in rat skeletal muscle.
When rat muscles were incubated in Ca2+-free media, their rates of protein break-down were significantly lower than in complete medium (2.58 mM Ca2+). Dantrolene and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, inhibitors of Ca2+ release from the sarcoplasmic reticulum, also reduced muscle proteolysis. When Ca2+ was added (up to 5.16 mM), proteolysis increased progressively up to 70% in the intact soleus and extensor digitorum longus muscles and up to 300% in the cut diaphragm preparation. Addition of Ca2+ did not affect the muscles' ATP or phosphocreatine content and increased protein synthesis slightly or not at all. Sr2+, Ba2+, and Mn2+ also increased proteolysis, but were less effective than Ca2+. Mg2+ inhibited the enhancement of proteolysis by Ca2+. This stimulation by Ca2+ was not affected by inhibitors of voltage-dependent Ca2+ channels, calmodulin, metalloendoproteases, microfilament or microtubule formation, or mersalyl. High Ca2+ levels also increased prostaglandin (PG) E2 production, although a rise in PGE2 did not appear essential for the increased proteolysis. The proteolysis induced by Ca2+ was prevented in muscles treated with Ep-475 or leupeptin. By contrast, these inhibitors of thiol proteases did not affect protein breakdown in Ca2+-free medium. Thus extracellular Ca2+ activates and Mg2+ inhibits a proteolytic pathway involving thiol proteases.
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002413:Cations, Divalent; D003546:Cysteine Endopeptidases; D003620:Dantrolene / Q000494:pharmacology; D003964:Diaphragm / Q000378:metabolism; D015232:Dinoprostone; D010450:Endopeptidases / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013324:Strontium / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D002121:Calcium Channel Blockers; D002413:Cations, Divalent; D009124:Muscle Proteins; D011458:Prostaglandins E; D011480:Protease Inhibitors; D001464:Barium; D014443:Tyrosine; D008345:Manganese; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D003620:Dantrolene; D008274:Magnesium; D015232:Dinoprostone; D002118:Calcium; D013324:Strontium