Mechanism of estrogen-mediated improvement in cardiac function after trauma-hemorrhage: p38-dependent normalization of cardiac Akt phosphorylation and glycogen levels

Jun Te Hsu, Wen Hong Kan, Ya Ching Hsieh, Mashkoor A. Choudhry, Martin G. Schwacha, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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 17β-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 3β 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.

Original languageEnglish (US)
Pages (from-to)372-378
Number of pages7
JournalShock
Volume30
Issue number4
DOIs
StatePublished - Oct 2008
Externally publishedYes

Keywords

  • Akt
  • Cardiac function
  • GLUT-4
  • Glycogen
  • p38 MAPK inhibitor

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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