Are lysosomal enzymes involved in rapid damage in vertebrate muscle cells? A study of the separate pathways leading to cellular damage.
Experiments with lysosomotropic agents suggest that the sarcotubular system subserves some of the functions of the lysosomal apparatus in frog skeletal muscle. Dinitrophenol or A23187 trigger lysosome labilization and myofilament damage in mammalian cardiac muscle. Lysolecithin labilizes isolated liver lysosomes, but has no action following phospholipase A2 activation in vivo. Zinc ions or a pHi of 7.5 do not protect against myofilament damage. In fractions from mammalian cardiac muscle, calcium and calmodulin do not cause lysosomal labilization whereas cGMP does but only at high concentration (10(-4) M). It is concluded that lysosomal hydrolases play no significant part in rapid muscle damage. It is suggested that rises in [Ca]i activate two separate pathways causing (i) myofilament damage; (ii) sarcolemmal (and possibly lysosomal) membrane damage via phospholipase A2 and lipoxygenase activity. Dinitrophenol triggers both pathways independently and thus may cause lysosome labilization. The possibility that the sarcoplasmic reticulum is the site generating myofilament damage is discussed.
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002402:Cathepsin D / Q000378:metabolism; D002474:Cell-Free System; D004140:Dinitrophenols / Q000494:pharmacology; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009132:Muscles / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D011896:Rana temporaria; D013347:Subcellular Fractions / Q000201:enzymology
D004140:Dinitrophenols; D008244:Lysophosphatidylcholines; D009712:Nucleotides, Cyclic; D000001:Calcimycin; D000135:Acid Phosphatase; D002402:Cathepsin D; D002118:Calcium