Caspase-9 activation revealed by semaphorin 7A cleavage is independent of apoptosis in the aged olfactory bulb.
Caspases are essential in multicellular organisms for inducing cell death during normal development and in the immune system. However, caspases can also trigger the degenerative process under certain conditions such as pathophysiological conditions and aging. Here, we identified Semaphorin 7A (Sema7A) as a novel substrate for caspase-9 that can be used to monitor caspase-9 activity in mice, and found nonapoptotic caspase-9 activation in the aged olfactory bulb (OB). Immunostaining of the OB for the caspase-9-cleaved form of Sema7A revealed abundant caspase-9-activated cells in 2-year-old (aged) but not in 2-month-old (young) mice. In fact, various regions of the aged brain, including the OB, exhibited an increased level of caspase-9 activity. However, the number of dying cells in the aged OB was, intriguingly, much lower (<20%) than in the OB of young mice. Furthermore, we found that the lower number dying cells in the aged OB was accompanied by a decreased expression of procaspase-3. These results suggest a survival strategy for aged OB neurons, which can no longer regenerate, in which the central apoptotic machinery downstream of caspase-9 is inactivated.
Ohsawa
Shizue
S
Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, and CREST, JST, Bunkyo-ku, Tokyo 113-0033, Japan.
Hamada
Shun
S
Asou
Hiroaki
H
Kuida
Keiuke
K
Uchiyama
Yasuo
Y
Yoshida
Hiroki
H
Miura
Masayuki
M
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D053453:Caspase 9 / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009830:Olfactory Bulb / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D039961:Semaphorins / Q000378:metabolism*; D013379:Substrate Specificity / Q000502:physiology
D015703:Antigens, CD; C485571:Sema7a protein, mouse; D039961:Semaphorins; D053453:Caspase 9