Metabolic myopathy produced by acute inhibition of glyceraldehyde-3-phosphate dehydrogenase with ortho-iodosobenzoic acid.
A previously developed model of exercise-induced muscle contracture using iodoacetate to inhibit glyceraldehyde-3-phosphate dehydrogenase in rat hindlimb muscles produced selective type II myofiber damage. Utilizing a modification of the same model system, rats were given intra-aortic ortho-iodosobenzoic acid (700 nmol/kg body weight), which cleaves tryptophanyl peptides from glyceraldehyde-3-phosphate dehydrogenase. Within 2-4 h, spontaneous electrically-silent contracture developed in the injected musculature resulting in a plantar-flexed position of the hindlimb. After 24 h, the extensor digitorum longus and tibialis anterior muscles appeared grossly swollen (edematous) and discolored. Microscopically, the extensor digitorum longus (composed predominantly of type II myofibers) contained many randomly scattered, damaged myofibers, reduced glycogen content, absent glyceraldehyde-3-phosphate dehydrogenase activity, interstitial edema and focal collections of mononuclear phagocytes. Damaged fibers showed degenerative changes and contained stainable intracellular calcium. On modified trichrome-stained sections, an outer red staining rim of material was identifiable in many fibers. The fibers of the soleus muscle (composed predominantly of type I myofibers) were not damaged, indicating a preferential ortho-iodosobenzoic acid effect on type II myofibers.
Locklear
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Department of Anatomical Sciences, University of Oklahoma College of Medicine, Oklahoma City 73190.
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D000818:Animals; D004139:Dinitrofluorobenzene / Q000633:toxicity; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors*; D007461:Iodoacetates / Q000633:toxicity; D019807:Iodoacetic Acid; D007463:Iodobenzoates / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009135:Muscular Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013439:Sulfhydryl Reagents / Q000633:toxicity
D007461:Iodoacetates; D007463:Iodobenzoates; D013439:Sulfhydryl Reagents; C008154:2-iodosobenzoic acid; D004139:Dinitrofluorobenzene; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D019807:Iodoacetic Acid