Estrogen may contribute to ischemic tolerance through modulation of cellular stress-related proteins.

Abstract

Ischemic tolerance describes a phenomenon whereby subcritical stimuli evoke cellular protective mechanisms resulting in increased tolerance to subsequent ischemia. In the present study we propose that the cytoprotective effects attributed to 17beta-estradiol and tunicamycin in an in vivo rodent model of ischemia are reflected by changes in neuronal tissue levels of m-calpain, HSP70, GRP94 and GRP78. Rats pretreated with 17beta-estradiol, tunicamycin or both demonstrated dose-dependent reductions in infarct area following 4 h of permanent middle cerebral artery occlusion (MCAO). Western blot analysis revealed that 4 h of MCAO was associated with decreased cortical expression of HSP70 and m-calpain and increased expression of GRP78. Pretreatment with 12.5 microg/kg 17beta-estradiol did not change this pattern of protein expression following MCAO. While GRP94 expression was elevated in sham-operated rats pretreated with 17beta-estradiol, the ensuing ischemic tolerance did not appear to be mediated by changes in cellular stress proteins. Pretreatment with 50 microg/kg tunicamycin significantly reduced HSP70 in cortical tissue samples taken from sham-operated rats and appeared to attenuate the threshold for activation of m-calpain in rats undergoing 4 h of MCAO. Lastly, a combined treatment in which rats undergoing MCAO were pretreated with both tunicamycin (24 h prior) and 17beta-estradiol (30 min prior) was associated with an attenuated stress response as indicated by reduced expression of GRP78 and GRP94 when compared to saline-treated controls. The results of this study suggest that the ischemic tolerance observed following MCAO in rats pretreated with either 17beta-estradiol or tunicamycin is likely mediated in part through differential effects on cellular stress proteins.

• Authors: Monique C Saleh, Barry J Connell, Tarek M Saleh
• Journal: Neuroscience research (Neurosci Res) Vol. 63 Issue 4 Pg. 273-9 (Apr 2009) ISSN: 0168-0102 [Print] Ireland
• PMID: 19367787 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogens
• GRP78 protein, rat
• HSP70 Heat-Shock Proteins
• Heat-Shock Proteins
• Membrane Proteins
• Molecular Chaperones
• glucose-regulated proteins
• Tunicamycin
• Estradiol
• Calpain
• m-calpain

Topics

• Animals
• Calpain (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Interactions
• Estradiol (pharmacology)
• Estrogens (pharmacology)
• Gene Expression Regulation (drug effects)
• HSP70 Heat-Shock Proteins (metabolism)
• Heat-Shock Proteins (metabolism)
• Infarction, Middle Cerebral Artery (pathology, prevention & control)
• Male
• Membrane Proteins (metabolism)
• Molecular Chaperones (metabolism)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Tunicamycin (pharmacology)