Major growth reduction and minor decrease in mitochondrial enzyme activity in cultured human muscle cells after exposure to zidovudine
✍ Scribed by Nicole H. Herzberg; Ina Zorn; Rob Zwart; Peter Portegies; Pieter A. Bolhuis
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 406 KB
- Volume
- 15
- Category
- Article
- ISSN
- 0148-639X
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✦ Synopsis
Zidovudine-induced rnitochondrial myopathy in AIDS patients reported recently might be due to inhibition of mitochondrial DNA polymerase y. We investigated the effect of zidovudine on proliferation, differentiation, activity of mitochondrial-and nuclear-encoded enzymes, and rnitochondrial DNA (mtDNA), in cultured human muscle cells. Marked inhibition of cell proliferation was found, even in the presence of low (10 pmol/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.