title: Mechanism of estrogen-mediated improvement in cardiac function after trauma-hemorrhage: p38-dependent normalization of cardiac Akt phosphorylation and glycogen levels.
abstract: Both p38 mitogen-activated protein kinase (p38) activation and protein kinase B (Akt) activation have been reported to regulate glucose transport during myocardial I/R. An increase in cardiac glycogen levels prevents myocardial injury in the ischemic or stressed heart. Although studies have shown that 17"-estradiol (E2)-mediated improvement in cardiac function after trauma-hemorrhage is via p38 activation, it remains unknown whether p38/Akt plays any role in regulation of cardiac glycogen levels under these conditions. To study this, male rats underwent trauma-hemorrhage(mean blood pressure, x40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats (n=6 per group) were treated with vehicle, E2 (1 mg/kg body weight), the p38 inhibitor SB203580 (2 mg/kg body weight), or E2 and SB203580. Various parameters were measured at 2 h after resuscitation. One-way ANOVA and Tukey test were used for statistical analysis, and differences were considered significant at P<0.05. The depressed cardiac function after trauma-hemorrhage was restored by E2 treatment (P<0.05). Administration of E2 after trauma-hemorrhage also normalized the p38/Akt phosphorylation, which was associated with restoration of cardiac glycogen, glycogen synthase kinase 3"activation, glucose transporter 4 translocation, and increased hexokinase II levels (all parameters, P<0.05). Inhibition of the p38 pathway abolished the E2-induced restoration in above parameters after trauma-hemorrhage. These results suggest that p38-dependent normalization of cardiac Akt phosphorylation and glycogen levels plays an important role in E2-mediated restoration of cardiac function after trauma-hemorrhage.
authors.affiliation: Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
authors.forename: Jun-Te
authors.initials: JT
authors.lastname: Hsu
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Kan
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006352:Heart Ventricles / Q000473:pathology; D006470:Hemorrhage / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D004967:Estrogens; D007093:Imidazoles; D011725:Pyridines; D006003:Glycogen; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580