Role of p38 mitogen-activated protein kinase pathway in estrogen-mediated cardioprotection following trauma-hemorrhage.
p38 mitogen-activated protein kinase (MAPK) activates a number of heat shock proteins (HSPs), including HSP27 and alpha(B)-crystallin, in response to stress. Activation of HSP27 or alpha(B)-crystallin is known to protect organs/cells by increasing the stability of actin microfilaments. Although our previous studies showed that 17beta-estradiol (E(2)) improves cardiovascular function after trauma-hemorrhage, whether the salutary effects of E(2) under those conditions are mediated via p38 MAPK remains unknown. Male rats (275-325 g body wt) were subjected to soft tissue trauma and hemorrhage (35-40 mmHg mean blood pressure for approximately 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were injected intravenously with vehicle, E(2) (1 mg/kg body wt), E(2) + the p38 MAPK inhibitor SB-203580 (2 mg/kg body wt), or SB-203580 alone, and various parameters were measured 2 h thereafter. Cardiac functions that were depressed after trauma-hemorrhage were returned to normal levels by E(2) administration, and phosphorylation of cardiac p38 MAPK, HSP27, and alpha(B)-crystallin was increased. The E(2)-mediated improvement of cardiac function and increase in p38 MAPK, HSP27, and alpha(B)-crystallin phosphorylation were abolished with coadministration of SB-203580. These results suggest that the salutary effect of E(2) on cardiac function after trauma-hemorrhage is in part mediated via upregulation of p38 MAPK and subsequent phosphorylation of HSP27 and alpha(B)-crystallin.
Hsu
Jun-Te
JT
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
Hsieh
Ya-Ching
YC
Kan
Wen Hong
WH
Chen
Jian Guo
JG
Choudhry
Mashkoor A
MA
Schwacha
Martin G
MG
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000005:Abdomen / Q000601:surgery; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D005440:Fluid Therapy; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D019106:Postoperative Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods; D015854:Up-Regulation; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects; D038203:alpha-Crystallin B Chain / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002316:Cardiotonic Agents; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D007093:Imidazoles; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D038203:alpha-Crystallin B Chain; D004958:Estradiol; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580