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

J. Biol. Chem., Vol. 280, Issue 28, 26339-26348, July 15, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/28/26339    most recent M414409200v1 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 Pedram, A. Articles by Levin, E. R. Search for Related Content PubMed PubMed Citation Articles by Pedram, A. Articles by Levin, E. R. Social Bookmarking                      What's this?

Estrogen Inhibits Cardiomyocyte Hypertrophy in Vitro

ANTAGONISM OF CALCINEURIN-RELATED HYPERTROPHY THROUGH INDUCTION OF MCIP1^*

Ali Pedram, Mahnaz Razandi¶, Mark Aitkenhead, and Ellis R. Levin¶||

From the ^¶Division of Endocrinology, Veterans Affairs Medical Center, Long Beach, California 90822 and the Departments of Medicine and Pharmacology, University of California, Irvine, California 92717

Evidence from in vivo studies suggests that some inputs to cardiac hypertrophy are opposed by the actions of estrogen. However, the mechanisms of E₂ action in this respect are mainly unknown. An important pathway that is utilized by multiple hypertrophic stimuli involves the activation of the tyrosine phosphatase, calcineurin (PP2B). Here we show that 17-estradiol (E₂) significantly prevents angiotensin II (AngII)- or endothelin-1 (ET-1)-induced new protein synthesis, skeletal muscle actin expression, and increased surface area in cultured rat cardiomyocytes. ET-1 stimulated calcineurin phosphatase activity, resulting in new protein synthesis, and both were prevented by E₂. E₂ induced the MCIP1 gene, an inhibitor of calcineurin activity, via phosphatidylinositol 3-kinase, transcriptional, and mRNA stability mechanisms. Small interfering RNA for MCIP1 significantly reversed both the E₂ restraint of protein synthesis and the inhibition of AngII-induced calcineurin activity. AngII-induced the translocation of the hypertrophic transcription factor, NF-AT, to the nucleus of the cardiomyocyte and stimulated NF-AT transcriptional activity. Both were prevented by E₂. AngII also stimulated the activation of ERK and protein kinase C, contributing to cardiac hypertrophy. E₂ inhibited these pathways, related to the stimulation of atrial natriuretic peptide production and secretion. Thus, restraint of calcineurin and kinase signaling to the hypertrophic program underlie these important effects of E₂.

Received for publication, December 22, 2004 , and in revised form, May 9, 2005.

^* This work was supported by grants from the Research Service of the Department of Veterans Affairs and by National Institutes of Health Grants HL-59890 and CA-100366 (to E. R. L.). 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.

^|| To whom correspondence should be addressed: Medical Service (111-I) Long Beach Veterans Affairs Medical Center, University of California, 5901 E. 7th St., Long Beach, CA 90822. Tel.: 562-826-5748; Fax: 562-826-5515; E-mail: ellis.levin{at}med.va.gov.

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

This article has been cited by other articles:

				E. R. Levin Rapid signaling by steroid receptors Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1425 - R1430. [Abstract] [Full Text] [PDF]

				E. Zhan, T. Keimig, J. Xu, E. Peterson, J. Ding, F. Wang, and X.-P. Yang Dose-dependent cardiac effect of oestrogen replacement in mice post-myocardial infarction Exp Physiol, August 1, 2008; 93(8): 982 - 993. [Abstract] [Full Text] [PDF]

				A. Pedram, M. Razandi, D. Lubahn, J. Liu, M. Vannan, and E. R. Levin Estrogen Inhibits Cardiac Hypertrophy: Role of Estrogen Receptor-{beta} to Inhibit Calcineurin Endocrinology, July 1, 2008; 149(7): 3361 - 3369. [Abstract] [Full Text] [PDF]

				A. Karatas, B. Hegner, L. J. de Windt, F. C. Luft, C. Schubert, V. Gross, Y. J. Akashi, D. Gurgen, U. Kintscher, A. C. da Costa Goncalves, et al. Deoxycorticosterone Acetate-Salt Mice Exhibit Blood Pressure-Independent Sexual Dimorphism Hypertension, April 1, 2008; 51(4): 1177 - 1183. [Abstract] [Full Text] [PDF]

				S. R. Hammes and E. R. Levin Extranuclear Steroid Receptors: Nature and Actions Endocr. Rev., December 1, 2007; 28(7): 726 - 741. [Abstract] [Full Text] [PDF]

				E. Hirsch, C. Costa, and E. Ciraolo Phosphoinositide 3-kinases as a common platform for multi-hormone signaling J. Endocrinol., August 1, 2007; 194(2): 243 - 256. [Abstract] [Full Text] [PDF]

				J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF]

				A. Kenessey and K. Ojamaa Thyroid Hormone Stimulates Protein Synthesis in the Cardiomyocyte by Activating the Akt-mTOR and p70S6K Pathways J. Biol. Chem., July 28, 2006; 281(30): 20666 - 20672. [Abstract] [Full Text] [PDF]

				M. Wang, P. Crisostomo, G. M. Wairiuko, and D. R. Meldrum Estrogen receptor-{alpha} mediates acute myocardial protection in females Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2204 - H2209. [Abstract] [Full Text] [PDF]

				J. K. Kim, A. Pedram, M. Razandi, and E. R. Levin Estrogen Prevents Cardiomyocyte Apoptosis through Inhibition of Reactive Oxygen Species and Differential Regulation of p38 Kinase Isoforms J. Biol. Chem., March 10, 2006; 281(10): 6760 - 6767. [Abstract] [Full Text] [PDF]

				W. Zhang, T. Anger, J. Su, J. Hao, X. Xu, M. Zhu, A. Gach, L. Cui, R. Liao, and U. Mende Selective Loss of Fine Tuning of Gq/11 Signaling by RGS2 Protein Exacerbates Cardiomyocyte Hypertrophy J. Biol. Chem., March 3, 2006; 281(9): 5811 - 5820. [Abstract] [Full Text] [PDF]