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.
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.
Yu
Huang-Ping
HP
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall, Room G094, Birmingham, AL 35294-0019, USA.
Shimizu
Tomoharu
T
Choudhry
Mashkoor A
MA
Hsieh
Ya-Ching
YC
Suzuki
Takao
T
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists; D047629:Estrogen Receptor beta / Q000819:agonists*; D000077267:Fulvestrant; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D010636:Phenols; D011422:Propionates / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000378:metabolism*; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation; D014947:Wounds and Injuries / Q000150:complications / Q000378:metabolism
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D020011:Protective Agents; D011720:Pyrazoles; D020845:Selective Estrogen Receptor Modulators; D014157:Transcription Factors; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D000077267:Fulvestrant; D004958:Estradiol