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

J. Biol. Chem., Vol. 282, Issue 22, 16244-16255, June 1, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/22/16244    most recent M700297200v1 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 Google Scholar Google Scholar Articles by Si, J. Articles by Cao, W. Search for Related Content PubMed PubMed Citation Articles by Si, J. Articles by Cao, W. Social Bookmarking                      What's this?

NADPH Oxidase NOX5-S Mediates Acid-induced Cyclooxygenase-2 Expression via Activation of NF-Bin Barrett's Esophageal Adenocarcinoma Cells^*

Jin Si, Xiaoying Fu, Jose Behar, Jack Wands, David G. Beer, Rhonda F. Souza^¶, Stuart J. Spechler^¶, David Lambeth^||, and Weibiao Cao¹

From the Department of Medicine, Rhode Island Hospital and Brown Medical School, Providence, Rhode Island 02903, the Department of Surgery, Section of General Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, the ^||Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322, and the ^¶Division of Gastroenterology, Dallas Veterans Affairs Medical Center and University of Texas Southwestern Medical School, Dallas, Texas 76235

We have shown that the NADPH oxidase NOX5-S may play an important role in the progression from Barrett's esophagus to esophageal adenocarcinoma (EA) by increasing cell proliferation and decreasing apoptosis. However, the mechanism of the acid-induced NOX5-S-mediated increase in cell proliferation is not known. We found that, in SEG1 EA cells, the acid-induced increase in prostaglandin E₂ (PGE₂) production was mediated by activation of cyclooxygenase-2 (COX2) but not by COX1. Acid treatment increased intracellular Ca²⁺, and a blockade of intracellular Ca²⁺ increase inhibited the acid-induced increase in COX2 expression and PGE₂ production. Knockdown of NOX5-S or NF-B1 p50 by their small interfering RNA significantly inhibited acid-induced COX2 expression and PGE₂ production in SEG1 cells. Acid treatment significantly decreased IB and increased luciferase activity when SEG1 cells were transfected with an NF-B in vivo activation reporter plasmid, pNF-B-Luc. In a novel Barrett's cell line overexpressing NOX5-S, IB was significantly reduced, and luciferase activity increased when these Barrett's cells were transfected with pNF-B-Luc. Overexpression of NOX5-S in Barrett's cells significantly increased H₂O₂ production, COX2 expression, PGE₂ production, and thymidine incorporation. The increase in thymidine incorporation occurring in NOX5-S-overexpressing Barrett's cells or induced by acid treatment in SEG1 EA cells was significantly decreased by COX2 inhibitors or small interfering RNA. We conclude that acid-induced COX2 expression and PGE₂ production depend on an increase in cytosolic Ca²⁺ and sequential activation of NOX5-S and NF-B in SEG1 cells. COX2-derived PGE₂ production may contribute to NOX5-S-mediated cell proliferation in SEG1 cells.

Received for publication, January 11, 2007 , and in revised form, March 1, 2007.

^* This work was supported in part by National Institutes of Health (NIH) COBRE Grant P20 RR17695 from the Institutional Development Award Program of the National Center for Research Resources, a component of the NIH and by NIDDK, NIH, Grant R21 DK073327-01. These data were presented in part at the 105th annual meeting of the American Gastroenterological Association, in New Orleans, LA, in May 2004. 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.

¹ To whom correspondence should be addressed: Dept. of Medicine, Brown Medical School and Rhode Island Hospital, 55 Claverick St., Rm. 337, Providence, RI 02903. Tel.: 401-444-8308; Fax: 401-444-5890; E-mail: wcao{at}hotmail.com.

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