HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 17, 11097-11106, April 25, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/17/11097    most recent M708909200v1 Submit a Letter to Editor 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harayama, T. Articles by Shimizu, T. Search for Related Content PubMed PubMed Citation Articles by Harayama, T. Articles by Shimizu, T. Social Bookmarking                      What's this?

Identification of a Novel Noninflammatory Biosynthetic Pathway of Platelet-activating Factor^*

Takeshi Harayama¹, Hideo Shindou¹², Rie Ogasawara, Akira Suwabe, and Takao Shimizu²³

From the Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 and the Department of Laboratory Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan

Platelet-activating factor (PAF) is a potent lipid mediator playing various inflammatory and physiological roles. PAF is biosynthesized through two independent pathways called the de novo and remodeling pathways. Lyso-PAF acetyltransferase (lyso-PAF AT) was believed to biosynthesize PAF under inflammatory conditions, through the remodeling pathway. The first isolated lyso-PAF AT (LysoPAFAT/LPCAT2) had consistent properties. However, we show in this study the finding of a second lyso-PAF AT working under noninflammatory conditions. We partially purified a Ca²⁺-independent lyso-PAF AT from mouse lung. Immunoreactivity for lysophosphatidylcholine acyltransferase 1 (LPCAT1) was detected in the active fraction. Lpcat1-transfected Chinese hamster ovary cells exhibited both LPCAT and lyso-PAF AT activities. We confirmed that LPCAT1 transfers acetate from acetyl-CoA to lyso-PAF by the identification of an acetyl-CoA (and other acyl-CoAs) interacting site in LPCAT1. We further showed that LPCAT1 activity and expression are independent of inflammatory signals. Therefore, these results suggest the molecular diversity of lyso-PAF ATs is as follows: one (LysoPAFAT/LPCAT2) is inducible and activated by inflammatory stimulation, and the other (LPCAT1) is constitutively expressed. Each lyso-PAF AT biosynthesizes inflammatory and physiological amounts of PAF, depending on the cell type. These findings provide important knowledge for the understanding of the diverse pathological and physiological roles of PAF.

Received for publication, October 29, 2007 , and in revised form, February 7, 2008.

^* This work was supported in part by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to T. S.) and the Japan Society for the Promotion of Science (Global Centers of Excellence Program). 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1–6 and primer sequences.

¹ Both authors contributed equally to this work.

² Supported by the Center for NanoBio Integration at the University of Tokyo.

³ To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Tel.: 81-3-5802-2925; Fax: 81-3-3813-8732; E-mail: tshimizu{at}m.u-tokyo.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Zhao, Y.-Q. Chen, S. Li, R. J. Konrad, and G. Cao The microsomal cardiolipin remodeling enzyme acyl-CoA lysocardiolipin acyltransferase is an acyltransferase of multiple anionic lysophospholipids J. Lipid Res., May 1, 2009; 50(5): 945 - 956. [Abstract] [Full Text] [PDF]

				K. Yuki, H. Shindou, D. Hishikawa, and T. Shimizu Characterization of mouse lysophosphatidic acid acyltransferase 3: an enzyme with dual functions in the testis J. Lipid Res., May 1, 2009; 50(5): 860 - 869. [Abstract] [Full Text] [PDF]

				H. Shindou, D. Hishikawa, T. Harayama, K. Yuki, and T. Shimizu Recent progress on acyl CoA: lysophospholipid acyltransferase research J. Lipid Res., April 1, 2009; 50(Supplement): S46 - S51. [Abstract] [Full Text] [PDF]

				H. Shindou and T. Shimizu Acyl-CoA:Lysophospholipid Acyltransferases J. Biol. Chem., January 2, 2009; 284(1): 1 - 5. [Abstract] [Full Text] [PDF]

				D. C. Tsoukatos, I. Brocheriou, V. Moussis, C. P. Panopoulou, E. D. Christofidou, S. Koussissis, S. Sismanidis, E. Ninio, and S. Siminelakis Platelet-activating factor acetylhydrolase and transacetylase activities in human aorta and mammary artery J. Lipid Res., October 1, 2008; 49(10): 2240 - 2249. [Abstract] [Full Text] [PDF]