title: Early decrease of mitochondrial DNA repair enzymes in spinal motor neurons of presymptomatic transgenic mice carrying a mutant SOD1 gene.
abstract: Growing evidence has recently shown that mutant SOD1 accumulate in the mitochondria and cause vacuolation in transgenic mice carrying mutant SOD1, an animal model of amyotrophic lateral sclerosis (ALS). In this study, the expressions of DNA repair enzymes, oxoguanine glycosylase 1 (ogg1), DNA polymerase beta (polbeta), and DNA polymerase gamma (polgamma) were examined in transgenic mice with an ALS-linked mutant SOD1 gene, a valuable model for human ALS. In presymptomatic Tg mice, the nuclear form of ogg1 was upregulated, whereas mitochondrial ogg1 remained at the same level. DNA polymerase was selectively downregulated in the mitochondria. This study suggests an impaired protective mechanism against oxidative stress in mitochondria. The expressions of these enzymes are predominant in spinal motor neurons, suggesting a mechanism of selective motor neuron death in this animal model of ALS.
authors: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. neuron@cc.okayama-u.ac.jp
authors: Tetsuro
authors: T
authors: Murakami
authors: Makiko
authors: M
authors: Nagai
authors: Kazunori
authors: K
authors: Miyazaki
authors: Nobutoshi
authors: N
authors: Morimoto
authors: Yasuyuki
authors: Y
authors: Ohta
authors: Tomoko
authors: T
authors: Kurata
authors: Yasushi
authors: Y
authors: Takehisa
authors: Tatsushi
authors: T
authors: Kamiya
authors: Koji
authors: K
authors: Abe
mesh_terms: D000818:Animals; D045647:DNA Glycosylases / Q000378:metabolism; D019951:DNA Polymerase beta / Q000378:metabolism; D000074002:DNA Polymerase gamma; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase; D005786:Gene Expression Regulation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000201:enzymology*; D009154:Mutation; D013116:Spinal Cord / Q000166:cytology*; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D019951:DNA Polymerase beta; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D045643:DNA Repair Enzymes