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PMID: 19741144 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Caspase-9 activation revealed by semaphorin 7A cleavage is independent of apoptosis in the aged olfactory bulb.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 29 ·No. 36 ·2009-09-09 ·Pages 11385-92

Ohsawa S, Hamada S, Asou H, Kuida K, Uchiyama Y, Yoshida H, Miura M

Abstract

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.

MeSH Terms
Aging/metabolism,pathology Animals Antigens, CD/metabolism Apoptosis/physiology Caspase 9/metabolism Enzyme Activation/physiology Mice Mice, Inbred C57BL Mice, Knockout Olfactory Bulb/cytology,enzymology,metabolism Semaphorins/metabolism Substrate Specificity/physiology
Chemicals
Antigens, CD Sema7a protein, mouse Semaphorins Caspase 9
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ohsawa Shizue
Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, and CREST, JST, Bunkyo-ku, Tokyo 113-0033, Japan.
Hamada Shun
Asou Hiroaki
Kuida Keiuke
Uchiyama Yasuo
Yoshida Hiroki
Miura Masayuki
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4780-08.2009
Published
2009-09-09
Pages
11385-92
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6665912
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.4780-08.2009 PMC Full Text View journal details
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