Fig 9. Salvage mechanisms triggered by E2 via Gper1 during I/R.
E2 binding to Gper1 may initially trigger protein kinase C (PKC) translocation. PKC could directly or via activation of MEK1/2/ERK1/2 pathway increase phosphorylation of GSK-3β, which in turn would inhibit mPTP opening resulting in cardioprotection. Chelerythrine chloride, inhibitor of PKC translocation; U0126, inhibitor of the MEK1/2/ERK1/2-pathway; and LY294002, inhibitor of PI-3K. E2 through Gper1 can also induce a transient activation of PI-3K/Akt pathway, but this activation does not play an important role in the acute E2 induced cardioprotection after I/R. Black arrows, pathways demonstrated in this work. Dashed arrows, putative pathways.?, unknown target.