Role of p38 mitogen-activated protein kinase pathway in estrogen-mediated cardioprotection following trauma-hemorrhage

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

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37 Scopus citations

Abstract

p38 mitogen-activated protein kinase (MAPK) activates a number of heat shock proteins (HSPs), including HSP27 and αB-crystallin, in response to stress. Activation of HSP27 or αB-crystallin is known to protect organs/cells by increasing the stability of actin microfilaments. Although our previous studies showed that 17β-estradiol (E2) improves cardiovascular function after trauma-hemorrhage, whether the salutary effects of E2 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 ∼90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were injected intravenously with vehicle, E2 (1 mg/kg body wt), E2 + 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 E2 administration, and phosphorylation of cardiac p38 MAPK, HSP27, and αB-crystallin was increased. The E 2-mediated improvement of cardiac function and increase in p38 MAPK, HSP27, and αB-crystallin phosphorylation were abolished with coadministration of SB-203580. These results suggest that the salutary effect of E2 on cardiac function after trauma-hemorrhage is in part mediated via upregulation of p38 MAPK and subsequent phosphorylation of HSP27 and αB-crystallin.

Original languageEnglish (US)
Pages (from-to)H2982-H2987
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number6
DOIs
Publication statusPublished - Jun 1 2007

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Keywords

  • Heat shock proteins
  • p38 mitogen-activated protein kinase inhibitor
  • α-crystallin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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