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

J. Biol. Chem., Vol. 283, Issue 3, 1628-1636, January 18, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/3/1628    most recent M708622200v1 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 Kono, N. Articles by Arai, H. Search for Related Content PubMed PubMed Citation Articles by Kono, N. Articles by Arai, H. Social Bookmarking                      What's this?

Protection against Oxidative Stress-induced Hepatic Injury by Intracellular Type II Platelet-activating Factor Acetylhydrolase by Metabolism of Oxidized Phospholipids in Vivo^*

Nozomu Kono, Takao Inoue, Yasukazu Yoshida^¶, Hiroyuki Sato^||, Tomokazu Matsusue^||, Hiroyuki Itabe^**, Etsuo Niki^¶, Junken Aoki, and Hiroyuki Arai¹

From the Graduate School of Pharmaceutical Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, ^¶Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, 1-8-31, Midorikawa, Ikeda, Osaka, 563-8577, ^||Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., 722 Uenohara, Jimba, Gotenba, Shizuoka, 412-8524, ^**Department of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Graduate School of Pharmaceutical Science, Tohoku University, 6-3 Aoba, Aramaki-aza, Aoba-ku, Sendai 980-8578, and PRESTO and CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan

Membrane phospholipids are susceptible to oxidation, which is involved in various pathological processes such as inflammation, atherogenesis, neurodegeneration, and aging. One enzyme that may help to remove oxidized phospholipids from cells is intracellular type II platelet-activating factor acetylhydrolase (PAF-AH (II)), which hydrolyzes oxidatively fragmented fatty acyl chains attached to phospholipids. Overexpression of PAF-AH (II) in cells or tissues was previously shown to suppress oxidative stress-induced cell death. In this study we investigated the functions of PAF-AH (II) by generating PAF-AH (II)-deficient (Pafah2^-/-) mice. PAF-AH (II) was predominantly expressed in epithelial cells such as kidney proximal and distal tubules, intestinal column epithelium, and hepatocytes. Although PAF-AH activity was almost abolished in the liver and kidney of Pafah2^-/- mice, Pafah2^-/- mice developed normally and were phenotypically indistinguishable from wild-type mice. However, mouse embryonic fibroblasts derived from Pafah2^-/- mice were more sensitive to tert-butylhydroperoxide treatment than those derived from wild-type mice. When carbon tetrachloride (CCl₄) was injected into mice, Pafah2^-/- mice showed a delay in hepatic injury recovery. Moreover, after CCl₄ administration, liver levels of the esterified form of 8-iso-PGF₂, a known in vitro substrate of PAF-AH (II), were higher in Pafah2^-/- mice than in wild-type mice. These results indicate that PAF-AH (II) is involved in the metabolism of esterified 8-isoprostaglandin F₂ and protects tissue from oxidative stress-induced injury.

Received for publication, October 17, 2007 , and in revised form, November 16, 2007.

^* This study was supported by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and by Core Research for Evolutional Science and Technology (CREST) and Precursory Research for Embryonic Science and Technology (PRESTO) of the Japan Science and Technology Corp. 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 a supplemental figure.

¹ To whom correspondence should be addressed: 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Tel.: 81-3-5841-4720; Fax: 81-3-3818-3173; E-mail: harai{at}mol.f.u-tokyo.ac.jp.

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

This article has been cited by other articles:

				T. M. McIntyre, S. M. Prescott, and D. M. Stafforini The emerging roles of PAF acetylhydrolase J. Lipid Res., April 1, 2009; 50(Supplement): S255 - S259. [Abstract] [Full Text] [PDF]

				S. C. Frasch, K. Z. Berry, R. Fernandez-Boyanapalli, H.-S. Jin, C. Leslie, P. M. Henson, R. C. Murphy, and D. L. Bratton NADPH Oxidase-dependent Generation of Lysophosphatidylserine Enhances Clearance of Activated and Dying Neutrophils via G2A J. Biol. Chem., November 28, 2008; 283(48): 33736 - 33749. [Abstract] [Full Text] [PDF]