Evidence of two mechanisms of prostaglandin release in an in vitro model of muscle damage. Possible therapeutic implications.
In spite of recent progress, treatment of muscle disease based on specific gene therapy is not yet available. An alternative approach is to develop treatment which affords non-specific protection against general factors involved in cell damage. This approach is used effectively to prevent neuronal damage in experimental brain ischemia in animals and has been proposed for human trials. The most effective intervention is the use of mild (35 degrees C) hypothermia. An in vitro model to study muscle cell damage employs the rat epitrochlearis muscle exposed to low concentrations of 2:4-dinitrophenol, an uncoupler of oxidative phosphorylation. The efflux of prostaglandin E2 (PGE2) from the muscle is used as an indicator of muscle damage. We now show that there are two types of PGE2 release. "Basal" efflux gradually declines with decreasing temperatures and is not affected by removal of calcium from the medium. The efflux of PGE2 in response to metabolic stress is dependent on the presence of calcium and is abolished by mild hypothermia of 35 degrees C. The latter effect suggests that cell death is muscle and neurons have features in common and that muscle may be a useful tissue in which to investigate this phenomenon further.
Majumdar
R
R
Division of Neurology, University of Alberta, Edmonton, Canada.
Cwik
V A
VA
Brooke
M H
MH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004140:Dinitrophenols / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D007773:Lactates / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004140:Dinitrophenols; D007773:Lactates; D011453:Prostaglandins; D000255:Adenosine Triphosphate; D015237:Dinoprost; D015232:Dinoprostone