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

J. Biol. Chem., Vol. 283, Issue 16, 10357-10365, April 18, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/16/10357    most recent M800269200v1 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 Google Scholar Articles by Davis, M. C. Articles by Distelhorst, C. W. PubMed PubMed Citation Articles by Davis, M. C. Articles by Distelhorst, C. W. Social Bookmarking                      What's this?

Dexamethasone-induced Inositol 1,4,5-Trisphosphate Receptor Elevation in Murine Lymphoma Cells Is Not Required for Dexamethasone-mediated Calcium Elevation and Apoptosis^*

From the Division of Hematology/Oncology, Departments of Medicine and Pharmacology, Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106

Glucocorticosteroid hormones, including dexamethasone, have diverse effects on immature lymphocyte function that ultimately lead to cell death. Previous studies established that glucocorticoid-induced alterations in intracellular calcium homeostasis promote apoptosis, but the mechanism by which glucocorticoids disrupt calcium homeostasis is unknown. Through gene expression array analysis, we found that dexamethasone induces a striking elevation of inositol 1,4,5-trisphosphate receptor (IP₃R) levels in two murine lymphoma cell lines, WEHI7.2 and S49.A2. IP₃R elevation was confirmed at both mRNA and protein levels. However, there was not a strong correlation between IP₃R elevation and altered calcium homeostasis in terms of either kinetics or dose response. Moreover, IP₃R knockdown, by either antisense or small interfering RNA, did not prevent either calcium disruption or apoptosis. Finally, DT40 lymphoma cells lacking all three IP₃R isoforms were just as sensitive to dexamethasone-induced apoptosis as wild-type DT40 cells expressing all three IP₃R isoforms. Thus, although alterations in intracellular calcium homeostasis contribute to glucocorticoid-induced apoptosis, these calcium alterations are not directly attributable to IP₃R elevation.

Received for publication, January 10, 2008 , and in revised form, February 12, 2008.

^* This work was supported by National Institutes of Health Grants R01 CA042755 (to C. W. D.) and T32 HL07147 (to M. C. D.). 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: Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106. Fax: 216-368-8919; E-mail: cwd{at}case.edu.

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