Bcl-2-linked apoptosis due to increase in NO synthase in brain of SAMP10.
We examined the linkage of nitric oxide (NO)-induced apoptosis to acceleration of brain aging of senescence-accelerated mouse prone 10 (SAMP10). The expression of neuronal nitric oxide synthase (nNOS) increased in the cerebral cortex of the brain of SAMP10 in an age-dependent manner and significantly higher levels of neuronal nitric oxide synthase (nNOS) were observed in both young and old SAMP10 as compared to age-matched controls. Moreover, a lower level of anti-apoptotic protein Bcl-2 and a higher level of pro-apoptotic protein cytochrome c in cytosol were observed in SAMP10 compared to the control. However, there was no significant difference in the expression of pro-apoptotic protein p53 between SAMP10 and the control. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive apoptotic cells were more abundant in the cerebral cortex of aged SAMP10 than in the control. The present results suggest that an age-dependent increase of NO by up-regulation of nNOS promotes the Bcl-2-linked apoptosis in the cerebral cortex of SAMP10 and this may cause the acceleration of brain aging of SAMP10.
Numata
Takuya
T
Department of Environmental Medicine and Informatics, Graduate School of Environmental Earth Science, Hokkaido University, Sapporo 060-0810, Japan.
Saito
Takeshi
T
Maekawa
Kazuyo
K
Takahashi
Yasumitsu
Y
Saitoh
Hiroshi
H
Hosokawa
Toshiyuki
T
Fujita
Hiroyoshi
H
Kurasaki
Masaaki
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D002540:Cerebral Cortex / Q000201:enzymology / Q000254:growth & development; D003574:Cytochrome c Group / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D012016:Reference Values
D003574:Cytochrome c Group; D019253:Proto-Oncogene Proteins c-bcl-2; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse