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

Abstract

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.

• Authors: Jun-Te Hsu, Ya-Ching Hsieh, Wen Hong Kan, Jian Guo Chen, Mashkoor A Choudhry, Martin G Schwacha, Kirby I Bland, Irshad H Chaudry
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 292 Issue 6 Pg. H2982-7 (Jun 2007) ISSN: 0363-6135 [Print] United States
• PMID: 17293487 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cardiotonic Agents
• HSP27 Heat-Shock Proteins
• Heat-Shock Proteins
• Hspb1 protein, rat
• Imidazoles
• Neoplasm Proteins
• Protein Kinase Inhibitors
• Pyridines
• alpha-Crystallin B Chain
• Estradiol
• p38 Mitogen-Activated Protein Kinases
• SB 203580

Topics

• Abdomen (surgery)
• Animals
• Blood Pressure (drug effects)
• Cardiotonic Agents (pharmacology)
• Disease Models, Animal
• Estradiol (pharmacology)
• Fluid Therapy
• HSP27 Heat-Shock Proteins
• Heat-Shock Proteins (metabolism)
• Imidazoles (pharmacology)
• Male
• Myocardium (enzymology, metabolism)
• Neoplasm Proteins (metabolism)
• Phosphorylation
• Postoperative Hemorrhage (drug therapy, metabolism, physiopathology, therapy)
• Protein Kinase Inhibitors (pharmacology)
• Pyridines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Resuscitation (methods)
• Up-Regulation
• Ventricular Function, Left (drug effects)
• Ventricular Pressure (drug effects)
• alpha-Crystallin B Chain (metabolism)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)