QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 9, 2009, 29(36):11385-11392; doi:10.1523/JNEUROSCI.4780-08.2009

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ohsawa, S. Articles by Miura, M. PubMed PubMed Citation Articles by Ohsawa, S. Articles by Miura, M.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Caspase-9 Activation Revealed by Semaphorin 7A Cleavage Is Independent of Apoptosis in the Aged Olfactory Bulb

Shizue Ohsawa,¹ Shun Hamada,³ Hiroaki Asou,⁴ Keiuke Kuida,⁵ Yasuo Uchiyama,⁶ Hiroki Yoshida,⁷ and Masayuki Miura^1,2

¹Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, and ²CREST, JST, Bunkyo-ku, Tokyo 113-0033, Japan, ³Laboratory for Cellular and Molecular Neuroscience, Department of Nutrition and Health Science, Faculty of Human Environmental Science, Fukuoka Women's University, Higashi-ku, Fukuoka 813-8529, Japan, ⁴Department of Neuro-Glia Cell Biology, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo 173-0015, Japan, ⁵Department of Biology, Vertex Pharmaceuticals, Cambridge, Massachusetts 02139, ⁶Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan, and ⁷Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan

Correspondence should be addressed to Masayuki Miura, Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Email: miura{at}mol.f.u-tokyo.ac.jp

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.

---

Received Oct. 4, 2008; revised May 24, 2009; accepted Aug. 4, 2009.

Correspondence should be addressed to Masayuki Miura, Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Email: miura{at}mol.f.u-tokyo.ac.jp

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help