Cardiac protection by mitoKATP channels is dependent on Akt translocation from cytosol to mitochondria during late preconditioning

Nauman Ahmad, Yigang Wang, Khawaja Husnain Haider, Boyu Wang, Zeeshan Pasha, Özge Uzun, Muhammad Ashraf

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

This investigation elucidates the Akt/mitochondrial ATP-sensitive K + (mitoKATP) channel signaling pathway in late pharmacological preconditioning, using the mitoKATP 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 μg/kg ip), an inhibitor of phosphatidylinositol 3-kinase, and BMS plus 5-hydroxydecanoic acid (5-HD, 5 mg/kg ip), an inhibitor of mitoKATP 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 mitoKATP channels is attributed to the translocation of phosphorylated Akt from cytosol to mitochondria.

Original languageEnglish (US)
Pages (from-to)H2402-H2408
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume290
Issue number6
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

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Keywords

  • Apoptosis
  • BMS-191095
  • Diazoxide
  • Mitochondrial ATP-sensitive K channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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