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

J. Biol. Chem., Vol. 282, Issue 33, 24166-24174, August 17, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/33/24166    most recent M703212200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kanayama, M. Articles by Uchida, K. Search for Related Content PubMed PubMed Citation Articles by Kanayama, M. Articles by Uchida, K. Social Bookmarking                      What's this?

Identification of a Serum Component That Regulates Cyclooxygenase-2 Gene Expression in Cooperation with 4-Hydroxy-2-nonenal^*

Masaya Kanayama, Satoru Yamaguchi, Takahiro Shibata, Noriyuki Shibata, Makio Kobayashi, Ryoji Nagai^¶, Hiroyuki Arai^||, Kazuhiko Takahashi^**, and Koji Uchida¹

From the Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan, Department of Pathology, Tokyo Women's Medical University, Tokyo 162-8666, Japan, ^¶Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan, ^||Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan, and ^**Department of Nutritional Biochemistry, Hokkaido Pharmaceutical University, Otaru 047-0264, Japan

Atherosclerosis is a disorder of lipid metabolism as well as a chronic inflammatory disease. Cyclooxygenase-2 (COX-2), an inducible isoform responsible for high levels of prostaglandin production during inflammation and immune responses, mediates a variety of biological actions involved in vascular pathophysiology. We have previously shown that COX-2 gene expression is dramatically induced by a lipid-derived endogenous electrophile, 4-hydroxy-2-nonenal (HNE) (Kumagai, T., Matsukawa, N., Kaneko, Y., Kusumi, Y., Mitsumata, M., and Uchida, K. (2004) J. Biol. Chem. 279, 48389–48396). In the present study, based on the finding that HNE induced COX-2 expression only in the serum-containing media, we characterized a serum component essential for the HNE-induced COX-2 induction and found that low density lipoprotein (LDL) that had been denatured by freeze-thawing or oxidized LDL might be involved in the COX-2 induction. Moreover, we characterized the cellular events triggered by the combined stimulus of HNE and oxidized LDL and established that COX-2 induction is regulated by two sets of signaling mechanisms, one for the up-regulation of the scavenger receptor CD36 by HNE and one for the CD36-mediated COX induction by oxidized LDL. These findings represent a demonstration of a link between lipoprotein modification and activation of the inflammatory potential of macrophages.

Received for publication, April 17, 2007 , and in revised form, May 30, 2007.

^* This work was supported by a research grant from the Ministry of Education, Culture, Sports, Science, and Technology and by the Center of Excellence (COE) Program in the 21st Century in Japan (to K. U.), by a research grant from the Institute for Advance Research, Nagoya University (to K. U.), and by the COE Program in the 21st Century in Japan (to K. U.). 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. S1–S5.

¹ To whom correspondence should be addressed: Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan. Tel.: 81-52-789-4127; Fax: 81-52-789-5741; E-mail: uchidak{at}agr.nagoya-u.ac.jp.

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

This article has been cited by other articles:

				N. Shanmugam, J. L. Figarola, Y. Li, P. M. Swiderski, S. Rahbar, and R. Natarajan Proinflammatory Effects of Advanced Lipoxidation End Products in Monocytes Diabetes, April 1, 2008; 57(4): 879 - 888. [Abstract] [Full Text] [PDF]