TY - JOUR
T1 - Early decrease of mitochondrial DNA repair enzymes in spinal motor neurons of presymptomatic transgenic mice carrying a mutant SOD1 gene
AU - Murakami, Tetsuro
AU - Nagai, Makiko
AU - Miyazaki, Kazunori
AU - Morimoto, Nobutoshi
AU - Ohta, Yasuyuki
AU - Kurata, Tomoko
AU - Takehisa, Yasushi
AU - Kamiya, Tatsushi
AU - Abe, Koji
N1 - Funding Information:
This work was partly supported by Grants-in-Aid for Scientific Research (Start-up) 188901112, (B) 18390257, (C) 18590957, (Hoga) 17659445 and the National Project on Protein Structural and Functional Analyses (Nakagawa A) from the Ministry of Education, Science, Culture and Sports of Japan, and by grants (Itoyama Y, Imai T and Kuzuhara S) from the Ministry of Health and Welfare of Japan.
PY - 2007/8/31
Y1 - 2007/8/31
N2 - 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 β (polβ), and DNA polymerase γ (polγ) 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.
AB - 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 β (polβ), and DNA polymerase γ (polγ) 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.
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U2 - 10.1016/j.brainres.2007.02.057
DO - 10.1016/j.brainres.2007.02.057
M3 - Article
C2 - 17434152
AN - SCOPUS:34247880172
VL - 1150
SP - 182
EP - 189
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1
ER -