Role of PI3Kα and sarcolemmal ATP-sensitive potassium channels in epoxyeicosatrienoic acid mediated cardioprotection

Journal of Molecular and Cellular Cardiology
Sri Nagarjun BatchuJohn M Seubert

Abstract

Epoxyeicosatrienoic acids (EETs) are cytochrome P450 epoxygenase metabolites of arachidonic acid that have known cardioprotective properties. While the mechanism(s) remains unknown, evidence suggests that phosphoinositide 3-kinase (PI3K) and sarcolemmal ATP-sensitive potassium channels (pmK(ATP)) are important. However the role of specific PI3K isoforms and corresponding intracellular mechanisms remains unknown. To study this, mice hearts were perfused in Langendorff mode for 40 min of baseline and subjected to 20 or 30 min of global no-flow ischemia followed by 40 min of reperfusion. C57BL6 mice perfused with 11,12-EET (1 μM) had improved postischemic recovery, whereas co-perfusion with PI3Kα inhibitor, PI-103 (0.1 μM), abolished the EET-mediated effect. In contrast, blocking of PI3Kβ or PI3Kγ isoforms failed to inhibit EET-mediated cardioprotection. In addition to the improved post-ischemic recovery, increased levels of p-Akt, decreased calcineurin activity and decreased translocation of proapoptotic protein BAD to mitochondria were noted in EET-treated hearts. Perfusion of 11,12-EET to Kir6.2 deficient mice (pmK(ATP)) failed to improve postischemic recovery, decrease calcineurin activity and translocation of proapoptotic pro...Continue Reading

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Citations

Apr 23, 2013·Drug Metabolism Reviews·Abdulaziz M S AlsaadAyman O S El-Kadi
Jan 7, 2014·Expert Opinion on Drug Metabolism & Toxicology·Nadia AspromonteMassimo Iacoviello
Jun 4, 2014·Journal of Molecular and Cellular Cardiology·Akinyemi Oni-OrisanJohn M Seubert
Mar 26, 2013·Toxicology Letters·Rawabi QadhiJohn M Seubert
Nov 27, 2014·Frontiers in Pharmacology·Victor SamokhvalovJohn M Seubert
Jun 11, 2016·Drug Metabolism Reviews·Michael Murray
Jan 4, 2017·The International Journal of Biochemistry & Cell Biology·Melissa E ReicheltJohn P Headrick
Jan 21, 2017·Prostaglandins & Other Lipid Mediators·K Lockhart JamiesonJohn M Seubert
Mar 29, 2019·Expert Opinion on Therapeutic Targets·Yuanyuan Cheng, Jianhui Rong
Jul 6, 2014·Fundamental & Clinical Pharmacology·Caroline BarauDidier Morin
Jan 1, 2019·Journal of Cellular and Molecular Medicine·Peng YeShao-Liang Chen
Jun 14, 2015·Physiological Reports·Jun QinAn Huang
Jul 4, 2018·International Journal of Molecular Sciences·Theresa AliwargaRheem A Totah

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