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Volume 9
Journal of Clinical & Experimental Cardiology
ISSN: 2155-9880
October 22-24, 2018 | Rome, Italy
27
th
European Cardiology Conference
Euro Cardiology 2018
October 22-24, 2018
Crucial role of mitofilin and cyclophilin D interaction in post-ischemic GPER1-induced
cardioprotection against ischemia-reperfusion injury
Jean C Bopassa
University of Texas Health Science Center, USA
W
e have recently shown that GPER1 (G protein-coupled estrogen receptor 1) mediates acute pre-ischemic estrogen-
induced protection of the myocardium from ischemia/reperfusion injury via a signalling cascade that includes PKC
translocation, ERK1/2/GSK-3β phosphorylation and inhibition of the mitochondrial permeability transition pore (mPTP)
opening. Here, we investigated the impact and mechanism involved in post-ischemic GPER1 activation in ischemia/
reperfusion injury. We determined whether GPER1 activation at the onset of reperfusion confers cardioprotective effects
by protecting against mitochondrial impairment. We found that post-ischemic E2 (17β-oestrogen) and G1 (both GPER1
agonists) administration to both male and female ovariectomized-rats reduced myocardial infarct size. Post-ischemic E2
administration preserved mitochondrial structural integrity and this was associated with a decrease in ROS production and
increased mitochondrial membrane potential, as well as an increase in the mitochondrial Ca2+ load required to induce mPTP
opening via activation of the MEK/ERK/GSK-3β axis, effects that were prevented by the GPER1 antagonist, G15. Interestingly,
this post-ischemic GPER1 cardioprotection was associated with the decrease degradation of the in the inner mitochondrial
membrane protein, referred to as mitofilin, during reperfusion, which protects the interaction between mitofilin-cyclophilin
D in the inner mitochondrial membrane resulting in the delay of the initiation of the mitochondrial permeability transition
(mPT) that is associated with the mPT pore opening. Additionally, we revealed that the mechanism of mitofilin degradation
during reperfusion is associated with its ubiquitination and also with the increase in calpain10 activity.
Biography
Jean C Bopassa pursued his PhD (2007) from Claude Bernard University Lyon 1, France and Postdoctoral studies from Harvard University School of Medicine
and the University of California Los Angeles (UCLA) School of Medicine respectively. He is currently the Director of a Cardiovascular Research Program in the
Department of Cellular and Integrative Physiology at the University of Texas Health Science San Antonio (UTHealth SA) School of Medicine. He has published more
than 25 papers in reputed journals, and has been serving as an Editorial Board Member of repute for several journals.
Jean C Bopassa, J Clin Exp Cardiolog 2018, Volume 9
DOI: 10.4172/2155-9880-C10-116