Experimental biology and medicine
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Exp. Biol. Med. (Maywood) · Jun 2010
Signaling pathways involved in postconditioning-induced cardioprotection of human myocardium, in vitro.
We examined the respective role and relationship between protein kinase C (PKC), mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channel and p38 mitogen-activated protein kinase (MAPK) in postconditioning of human myocardium, in vitro. Isometrically contracting, isolated human right atrial trabeculae were exposed to 30 min hypoxia and 60 min reoxygenation. Phorbol 12-myristate 13-acetate (a PKC activator), diazoxide (a mitoK(ATP) opener) and anisomycin (a p38 MAPK activator) were superfused in early reoxygenation alone and with calphostin C (a PKC inhibitor), 5-hydroxy-decanoate (5-HD, a mitoK(ATP) channel inhibitor) and SB 202190 (a p38 MAPK inhibitor). ⋯ In conclusion, PKC activation, opening of mitoK(ATP) channels and p38 MAPK activation in early reoxygenation induced the postconditioning of human myocardium, in vitro. Furthermore, PKC activation was upstream of the opening of mitoK(ATP) channels; p38 MAPK acted on PKC. Therefore, mitoK(ATP) and p38 MAPK seemed to be involved in two independent pathways.