Peroxide production and apoptosis in cultured cells carrying mtDNA mutation causing encephalomyopathy.
When cybrids with a point mutation, which locates in the tRNALeu(UUR) gene of mtDNA and causes a mitochondrial encephalomyopathy (MELAS syndrome), were exposed to a high concentration of oxygen (95%), the peroxide production markedly increased by 6 h of oxygen exposure, whereas the peroxide production was similar among the cybrids under a normal concentration of oxygen. The peroxide production by oxygen exposure was enhanced particularly in cybrids with high proportions of the mutant mtDNA and low respiratory capacities. The appearance of apoptotic cells by oxygen exposure was high in cybrids with the impaired respiratory function due to the mutation. An antioxidant NAC successfully suppressed both the peroxide production and apoptosis. These results imply that the peroxide production plays an important role in inducing apoptosis in cells carrying the mtDNA mutation causing encephalomyopathy.
Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
J
J
Zhang
M
M
Yoneda
K
K
Naruse
H J
HJ
Borgeld
J S
JS
Gong
S
S
Obata
M
M
Tanaka
K
K
Yagi
D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000235:genetics*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006822:Hybrid Cells; D017241:MELAS Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010100:Oxygen / Q000494:pharmacology; D010545:Peroxides / Q000378:metabolism*; D017354:Point Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism
D004272:DNA, Mitochondrial; D016166:Free Radical Scavengers; D010545:Peroxides; D017382:Reactive Oxygen Species; D010100:Oxygen; D000111:Acetylcysteine