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Major growth reduction and minor decrease in mitochondrial enzyme activity in cultured human muscle cells after exposure to zidovudine
Author(s) -
Herzberg Nicole H.,
Zorn Ina,
Zwart Rob,
Portegies Peter,
Bolhuis Pieter A.
Publication year - 1992
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.880150613
Subject(s) - zidovudine , mitochondrial dna , biology , cytochrome c oxidase , mitochondrion , microbiology and biotechnology , mitochondrial toxicity , mitochondrial myopathy , cell growth , enzyme , cell culture , citrate synthase , biochemistry , virology , gene , virus , genetics , viral disease
Zidovudine‐induced mitochondrial myopathy in AIDS patients reported recently might be due to inhibition of mitochondrial DNA polymerase γ. We investigated the effect of zidovudine on proliferation, differentiation, activity of mitochondrial‐ and nuclear‐encoded enzymes, and mitochondrial DNA (mtDNA), in cultured human muscle cells. Marked inhibition of cell proliferation was found, even in the presence of low (10 μmol/L) zidovudine concentrations. Enzyme activity of the nuclear‐encoded mitochondrial citrate synthase was not affected, and the partially mitochondrial‐encoded cytochrome c oxidase was not decreased, except only after exposure to high concentrations (5 mmol/L) zidovudine. No decrease of mtDNA content and no mtDNA deletions were found in zidovudine‐exposed muscle cells. We propose that the effect of zidovudine on muscle, seen in zidovudine‐treated AIDS patients, results mainly from decrease in proliferation of muscle cells rather than inhibition of mtDNA replication.