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PMID: 3136925 Published · ppublish English Journal Article

Are lysosomal enzymes involved in rapid damage in vertebrate muscle cells? A study of the separate pathways leading to cellular damage.

Cell and tissue research ·Vol. 253 ·No. 2 ·1988-08-00 ·Pages 447-55

Duncan CJ, Rudge MF

Abstract

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.

MeSH Terms
Acid Phosphatase/metabolism Animals Calcimycin/pharmacology Calcium/pharmacology Cathepsin D/metabolism Cell-Free System Dinitrophenols/pharmacology Guinea Pigs Hydrogen-Ion Concentration In Vitro Techniques Liver/drug effects,enzymology Lysophosphatidylcholines/pharmacology Lysosomes/drug effects,enzymology,ultrastructure Mice Mice, Inbred BALB C Microscopy, Electron Muscles/drug effects,enzymology,ultrastructure Myocardium/enzymology,ultrastructure Nucleotides, Cyclic/pharmacology Rana temporaria Subcellular Fractions/enzymology
Chemicals
Dinitrophenols Lysophosphatidylcholines Nucleotides, Cyclic Calcimycin Acid Phosphatase Cathepsin D Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Duncan C J
Department of Zoology, University of Liverpool, United Kingdom.
Rudge M F
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Article Info
Journal
Cell and tissue research
Abbr.
Cell Tissue Res
ISSN
0302-766X
DOI
10.1007/BF00222302
Published
1988-08-00
Pages
447-55
Language
English
Region
Germany
NLM ID
0417625
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00222302 View journal details
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