Objekt-Metadaten

Reduction of apoptosis and preservation of mitochondrial integrity under ischemia/reperfusion injury is mediated by estrogen receptor β
Schubert, Carola ;  Raparelli, Valeria ;  Westphal, Christina ;  Dworatzek, Elke ;  Petrov, George ;  Kararigas, Georgios ;  Regitz-Zagrosek

HaupttitelReduction of apoptosis and preservation of mitochondrial integrity under ischemia/reperfusion injury is mediated by estrogen receptor β
AutorSchubert, Carola
AutorRaparelli, Valeria
AutorWestphal, Christina
AutorDworatzek, Elke
AutorPetrov, George
AutorKararigas, Georgios
AutorRegitz-Zagrosek
Seitenzahl9 S.
Freie SchlagwörterApoptosis; Estrogen receptor β; Ischemia/reperfusion; Mitochondria; Myosin light chain
DDC610 Medizin und Gesundheit
Auch erschienen inBiology of Sex Differences. - 7 (2016), Artikel Nr. 53
ZusammenfassungBackground

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 17β-estradiol (E2) as well as a specific ERβ agonist improve cardiac recovery through estrogen receptor (ER)β-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 ERβ agonist (ERβA). Isolated hearts were perfused for 20min prior to 30min global ischemia followed by 40min reperfusion.

Results

Compared with controls, ERβA 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. ERβA 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 ERβA 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 ERβA treated groups.

Conclusions

Activation of ERβ 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 ERβ agonist. Furthermore, E2 modulates MLC2 activation after I/R independent of ERβ.
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Fachbereich/EinrichtungMedizinische Fakultät Charité - Universitätsmedizin Berlin
Erscheinungsjahr2016
Dokumententyp/-SammlungenWissenschaftlicher Artikel
SpracheEnglisch
RechteCreative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Anmerkungen des AutorsDer Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
Erstellt am03.11.2016 - 10:58:00
Letzte Änderung03.11.2016 - 11:04:12
 
Statische URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000025653
DOI10.1186/s13293-016-0104-8
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