Skeletal muscle mitochondria from azt-treated rats have a
diminished response to chronic electrical stimulation.
McCurdy, Daniel T., John M. Kennedy.
Department of Physiology and BioPhysics, University of Illinois at
Chicago, 901 S. Wolcott, Chicago, IL, 60612
APStracts 3:0092A, 1996.
AZT-mediated inhibition of DNA polymerase [gamma] function has been
proposed to cause a myopathy by reducing mitochondrial DNA (mtDNA)
replication. Repeated bouts of exercise stimulate an increase in
mtDNA replication, mitochondrial content, and mitochondrial volume
fraction. Therefore, adaptation of rat skeletal muscle (tibialis
anterior,TA) mitochondria exposed to AZT (35 days, 1 mg/ml) and then
8 h/day electrical stimulation (7, 14, 21 days) with continued AZT
treatment was examined. Fourteen and 21 days of stimulation increased
TA cytochrome oxidase (COX) activity, mtDNA, COX subunit III and VIc
mRNA levels in both groups. The TA COX activity and COX III mRNA
increases after 14 and 21 days of stimulation were diminished in AZT
-treated rats. TA glyceraldhyde 3-phosphate dehydrogenase was reduced
in normal rats after chronic stimulation but was unchanged in AZT
-treated rats. Chronic stimulation increased the mitochondrial volume
fraction by 80% in normal rats and 40% in AZT-treated rats. These
results indicate diminution, but not complete inhibition, of
mitochondrial adaptation by AZT-treated skeletal muscle in response
to stimulation.
Received 14 November 1995; accepted in final form 5 February
1996.
APS Manuscript Number A1197-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96