title: Cardiac protection by mitoKATP channels is dependent on Akt translocation from cytosol to mitochondria during late preconditioning.
abstract: This investigation elucidates the Akt/mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel signaling pathway in late pharmacological preconditioning, using the mitoK(ATP) channel openers BMS-191095 (BMS) and diazoxide (DE). BMS (1 mg/kg ip) and DE (7 mg/kg ip) alone or BMS plus wortmannin (WTN, 15 microg/kg ip), an inhibitor of phosphatidylinositol 3-kinase, and BMS plus 5-hydroxydecanoic acid (5-HD, 5 mg/kg ip), an inhibitor of mitoK(ATP) channels, were administered to male mice. Twenty-four hours later, hearts were isolated and subjected to 40 min of ischemia and 120 min of reperfusion via Langendorff's apparatus. Both BMS and DE reduced left ventricular end-diastolic pressure and increased left ventricular developed pressure as well as reduced LDH release. Coadministration of BMS and WTN abolished the beneficial effects of BMS on cardiac function. Moreover, BMS and DE accelerated Akt phosphorylation in cardiac tissue as determined by Western blot analysis and also significantly reduced apoptosis compared with ischemic control. WTN significantly suppressed BMS-induced Akt phosphorylation, whereas 5-HD had no effect on Akt phosphorylation in cytosol, and the effect of BMS on apoptosis was abolished. It is concluded that the cardioprotective effect by mitoK(ATP) channels is attributed to the translocation of phosphorylated Akt from cytosol to mitochondria.
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267-0529, USA.
authors: Nauman
authors: N
authors: Ahmad
authors: Yigang
authors: Y
authors: Wang
authors: Khawaja Husnain
authors: KH
authors: Haider
authors: Boyu
authors: B
authors: Wang
authors: Zeeshan
authors: Z
authors: Pasha
authors: Ozge
authors: O
authors: Uzun
authors: Muhammad
authors: M
authors: Ashraf