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Mechanism of cardioprotection following trauma-hemorrhagic shock by a selective estrogen receptor-beta agonist: up-regulation of cardiac heat shock factor-1 and heat shock proteins.

Abstract：

:Although 17beta-estradiol (E2) administration following trauma-hemorrhage (T-H) improves cardiac function in male rodents, it is not known whether the salutary effects of E2 are mediated via estrogen receptor (ER)-alpha or ER-beta, and whether cardiac heat shock proteins (Hsp) are affected by E2 administration. Male Sprague-Dawley rats underwent T-H (mean BP 40 mmHg for 90 min, then resuscitation). ER-alpha agonist propyl pyrazole triol (PPT) (5 microg/kg), ER-beta agonist diarylpropiolnitrile (DPN) (5 microg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. At 24 h after T-H or sham operation, cardiac output (CO), stroke volume (SV), mean blood pressure, and +/- dP/dt max were measured (n=6 rats per group). Cardiac Hsp32, 60, 70, and 90 mRNA/protein expressions and heat shock factor (HSF)-1 DNA binding activity were determined. One-way ANOVA and Tukey's test were used for statistical analysis. CO, SV and +/- dP/dt(max) decreased significantly after T-H, however, administration of ER-beta agonist DPN after T-H restored the above parameters. Moreover, DPN treatment prevented T-H-mediated decrease in Hsp60 mRNA/protein and Hsp90 protein expressions in the heart. Hsp32 and Hsp70 mRNA/protein expression and HSF-1 DNA binding activity in the hearts were increased even above the shams in DPN treated T-H rats. In contrast, no significant change in the above parameters was observed in T-H rats treated with ER-alpha agonist PPT. Thus, the salutary effects of E2 on cardiac function are mediated via ER-beta and ER-beta-induced up-regulation of Hsp likely plays a significant role in the E2-mediated cardioprotection after T-H.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Yu HP,Shimizu T,Choudhry MA,Hsieh YC,Suzuki T,Bland KI,Chaudry IH

doi

10.1016/j.yjmcc.2005.10.001

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

185-94

issue

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(05)00314-7

journal_volume

pub_type

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Mechanism of cardioprotection following trauma-hemorrhagic shock by a selective estrogen receptor-beta agonist: up-regulation of cardiac heat shock factor-1 and heat shock proteins.