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

This Article Full Text Free Full Text (PDF) Free Alert me when this article is cited Alert me if a correction is posted 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 Hsieh, Y.-C. Articles by Chaudry, I. H. Search for Related Content PubMed PubMed Citation Articles by Hsieh, Y.-C. Articles by Chaudry, I. H.

Inhibition of cardiac PGC-1 expression abolishes ERß agonist-mediated cardioprotection following trauma-hemorrhage

Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA

¹Correspondence: Center for Surgical Research, University of Alabama at Birmingham, 1670 University Blvd, Volker Hall, Rm. G094, Birmingham, Alabama 35294-0019 USA. E-mail: ichaudry{at}surg.uab.edu

PGC-1 (peroxisome proliferator-activated receptor [PPAR] coactivator-1) activates PPAR and mitochondrial transcription factor A (Tfam), which regulate proteins, fatty acid and ATP metabolism (i.e., FAT/CD36, MCAD, and COX I). Recently we found that the salutary effects of estradiol (E2) on cardiac function following trauma-hemorrhage (T-H) are mediated via estrogen receptor (ER)ß. In this study we tested the hypothesis that ERß-mediated cardioprotection is induced via up-regulation of PGC-1 through PPAR or Tfam-dependent pathway. Male rats underwent T-H and received ER agonist propylpyrazole-triol (PPT), ERß agonist diarylpropionitrile (DPN), E2, or vehicle. Another group was treated with antisense PGC-1 oligonucleotides prior to administration of DPN. E2 and DPN treatments attenuated the decrease in cardiac mitochondrial ATP, abrogated the T-H-induced lipid accumulation, and normalized PGC-1, PPAR, FAT/CD36, MCAD, Tfam, and COX I after T-H. In contrast, PPT administration did not abrogate lipid accumulation. Moreover, in PPT-treated animals mitochondrial ATP remained significantly lower than those observed in DPN- or E2-treated animals. Prior administration of antisense PGC-1 prevented DPN-mediated cardioprotection and increase in ATP levels and Tfam but not in PPAR following T-H. These findings suggest that the salutary effects of E2 on cardiac function following T-H are mediated via ERß up-regulation of PGC-1 through Tfam-dependent pathway.—Hsieh, Y.-C., Choudhry, M. A., Yu, H.-P., Shimizu, T., Yang, S., Suzuki, T., Chen, J., Bland, K. I., Chaudry, I. H. Inhibition of cardiac PGC-1 expression abolishes ERß agonist-mediated cardioprotection following trauma-hemorrhage.

Key Words: hemorrhagic shock • heart • estrogen receptor • mitochondria

This article has been cited by other articles:

				T. Suzuki, T. Shimizu, H.-P. Yu, Y.-C. Hsieh, M. A. Choudhry, K. I. Bland, and I. H. Chaudry Estrogen receptor-{alpha} predominantly mediates the salutary effects of 17beta-estradiol on splenic macrophages following trauma-hemorrhage Am J Physiol Cell Physiol, September 1, 2007; 293(3): C978 - C984. [Abstract] [Full Text] [PDF]

				E. Murphy and C. Steenbergen Gender-based differences in mechanisms of protection in myocardial ischemia-reperfusion injury Cardiovasc Res, August 1, 2007; 75(3): 478 - 486. [Abstract] [Full Text] [PDF]

				T. Suzuki, T. Shimizu, H.-P. Yu, Y.-C. Hsieh, M. A. Choudhry, and I. H. Chaudry Salutary effects of 17beta-estradiol on T-cell signaling and cytokine production after trauma-hemorrhage are mediated primarily via estrogen receptor-{alpha} Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2103 - C2111. [Abstract] [Full Text] [PDF]

				D. R. Meldrum G-Protein-Coupled Receptor 30 Mediates Estrogen's Nongenomic Effects after Hemorrhagic Shock and Trauma Am. J. Pathol., April 1, 2007; 170(4): 1148 - 1151. [Full Text] [PDF]

				Y.-C. Hsieh, H.-P. Yu, M. Frink, T. Suzuki, M. A. Choudhry, M. G. Schwacha, and I. H. Chaudry G Protein-Coupled Receptor 30-Dependent Protein Kinase A Pathway Is Critical in Nongenomic Effects of Estrogen in Attenuating Liver Injury after Trauma-Hemorrhage Am. J. Pathol., April 1, 2007; 170(4): 1210 - 1218. [Abstract] [Full Text] [PDF]

				T. Suzuki, T. Shimizu, H.-P. Yu, Y.-C. Hsieh, M. A. Choudhry, M. G. Schwacha, and I. H. Chaudry Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage J Appl Physiol, January 1, 2007; 102(1): 163 - 168. [Abstract] [Full Text] [PDF]