Detection of a mouse OGG1 fragment during caspase-dependent apoptosis: oxidative DNA damage and apoptosis.
We investigated the expression of mouse 8-oxoguanine DNA glycosylase 1 (mOGG1) in mouse non-parenchymal hepatocytes (NCTC) during etoposide- or mitomycin C (MMC)-induced apoptosis. We observed mOGG1 fragmentation in apoptotic cells. The apoptosis accompanying the fragmentation of mOGG1 was caspase-dependent. The mOGG1 fragment existed in both the cytoplasm and nucleus of the etoposide-treated NCTC, indicating that the mOGG1 fragment could be transferred into the nucleus. In addition, 8-hydroxyguanine (8-OH-Gua, 7,8-dihydro-8-oxoguanine) accumulated in the DNA of NCTC treated with etoposide, suggesting that the mOGG1 fragment might not function as a normal repair enzyme in etoposide-treated NCTC. Although we have not clarified in detail the mechanism and the significance of the mOGG1 fragmentation, further study of the fragmentation of DNA repair enzymes might provide insights into the relationship between oxidative DNA damage and apoptosis.
Hirano
Takeshi
T
Department of Environmental Oncology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.
Kawai
Kazuaki
K
Ootsuyama
Yuko
Y
Orimo
Hiroshi
H
Kasai
Hiroshi
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000494:pharmacology*; D002467:Cell Nucleus / Q000737:chemistry; D004249:DNA Damage; D045647:DNA Glycosylases / Q000096:biosynthesis* / Q000378:metabolism*; D004260:DNA Repair; D005047:Etoposide / Q000494:pharmacology; D022781:Hepatocytes; D015151:Immunoblotting; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D018384:Oxidative Stress; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D016685:Mitomycin; D005047:Etoposide; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D020169:Caspases