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Reduction of apoptosis and preservation of mitochondrial integrity under ischemia/reperfusion injury is mediated by estrogen receptor β

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Item Type:Article
Title:Reduction of apoptosis and preservation of mitochondrial integrity under ischemia/reperfusion injury is mediated by estrogen receptor β
Creators Name:Schubert, C. and Raparelli, V. and Westphal, C. and Dworatzek, E. and Petrov, G. and Kararigas, G. and Regitz-Zagrosek, V.
Abstract:BACKGROUND: Estrogen improves cardiac recovery after ischemia/reperfusion (I/R) by yet incompletely understood mechanisms. Mitochondria play a crucial role in I/R injury through cytochrome c-dependent apoptosis activation. We tested the hypothesis that 17{beta}-estradiol (E2) as well as a specific ER{beta} agonist improve cardiac recovery through estrogen receptor (ER){beta}-mediated mechanisms by reducing mitochondria-induced apoptosis and preserving mitochondrial integrity. METHODS: We randomized ovariectomized C57BL/6N mice 24h before I/R to pre-treatment with E2 or a specific ER{beta} agonist (ER{beta}A). Isolated hearts were perfused for 20min prior to 30min global ischemia followed by 40min reperfusion. RESULTS: Compared with controls, ER{beta}A and E2 treated groups showed a significant improvement in cardiac recovery, i.e. an increase in left ventricular developed pressure, dP/dtmax and dP/dtmin. ER{beta}A and E2 pre-treatment led to a significant reduction in apoptosis with decreased cytochrome c release from the mitochondria and increased mitochondrial levels of anti-apoptotic Bcl2 and ACAA2. Protein levels of mitochondrial translocase inner membrane (TIM23) and mitochondrial complex I of respiratory chain were increased by ER{beta}A and E2 pre-treatment. Furthermore, we found a significant increase of myosin light chain 2 (MLC2) phosphorylation together with ERK1/2 activation in E2, but not in ER{beta}A treated groups. CONCLUSIONS: Activation of ER{beta} is essential for the improvement of cardiac recovery after I/R through the inhibition of apoptosis and preservation of mitochondrial integrity and can be a achieved by a specific ER{beta} agonist. Furthermore, E2 modulates MLC2 activation after I/R independent of ER{beta}.
Keywords:Apoptosis, Estrogen receptor {beta}, Ischemia/Reperfusion, Mitochondria, Myosin Light Chain, Animals, Mice
Source:Biology of Sex Differences
Publisher:BioMed Central
Page Range:53
Date:23 September 2016
Official Publication:https://doi.org/10.1186/s13293-016-0104-8
PubMed:View item in PubMed

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