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J. Biol. Chem., Vol. 280, Issue 24, 23203-23214, June 17, 2005

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Neuronal Expression and Neuritogenic Action of Group X Secreted Phospholipase A₂^*

Seiko Masuda, Makoto Murakami**, Yasukazu Takanezawa, Junken Aoki, Hiroyuki Arai, Yukio Ishikawa¶, Toshiharu Ishii¶, Manabu Arioka||, and Ichiro Kudo

From the Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, ^**The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan, Graduate School of Pharmaceutical Sciences, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, the ^||Department of Biotechnology, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, and the ^¶Department of Pathology, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ohta-ku, Tokyo 143-8540, Japan

Although individual mammalian secreted phospholipase A₂ (sPLA₂) enzymes exhibit unique tissue and cellular distributions, the cell type-specific functions of each enzyme remain largely unknown. In this study, we found by immunohistochemistry that group X sPLA₂ (sPLA₂-X) is uniquely located in the peripheral neuronal fibers, an observation that was supported by detection of its transcript and protein in the neuronal cell line PC12 and in primary dorsal root ganglia neurons. Adenoviral expression of sPLA₂-X in PC12 cells facilitated neurite outgrowth, particularly when combined with a suboptimal concentration of nerve growth factor. In neuronally differentiated PC12 cells, sPLA₂-X was preferentially localized in the Golgi apparatus and growth cones, and proteolytic conversion of the proenzyme to mature enzyme mainly occurred after the secretion process. The neurite-extending ability of sPLA₂-X depended on the production of its catalytic product, lysophosphatidylcholine. Moreover, nerve growth factor-induced neurite extension of PC12 cells was modestly but significantly attenuated by an anti-sPLA₂-X antibody or by a small interfering RNA for sPLA₂-X. These observations suggest the potential contribution of sPLA₂-X to neuronal differentiation, and possibly repair, under certain conditions.

Received for publication, January 26, 2005 , and in revised form, March 18, 2005.

^* This work was supported by grants-in aid for scientific research from the Ministry of Education, Science, Culture, Sports and Technology of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. Tel.: 81-3-3794-8197; Fax: 81-3-3784-8245; E-mail: mako{at}pharm.showa-u.ac.jp and mako{at}rinshoken.or.jp.

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