Multiple antiapoptotic targets of the PI3K/Akt survival pathway are activated by epoxyeicosatrienoic acids to protect cardiomyocytes from hypoxia/anoxia

• DOI: 10.1152/ajpheart.00979.2007
• Publication Date: 2007-12-01T01:34:10Z
• Authors: Anuradha Dhanasek...; Stephanie K. Grue...; J. Noelle Buonacc...; Rong Zhang; Garrett J. Gross; John R. Falck; Paresh K. Patel; Elizabeth R. Jacobs; Meetha Medhora
• Keywords: Hypoxia

Epoxyeicosatrienoic acids (EETs) reduce infarction of the myocardium after ischemia-reperfusion injury to rodent and dog hearts mainly by opening sarcolemmal mitochondrial potassium channels. Other mediators for action EET have been proposed, although no definitive pathway or mechanism has yet reported. Using cultured cells from two species, immortalized myocytes a mouse atrial lineage (HL-1) primary derived neonatal rat hearts, we observed that pretreatment with EETs (1 μM 14,15-, 11,12-, 8,9-EET) attenuated apoptosis exposure hypoxia reoxygenation (H/R). also preserved functional beating in culture H/R. We demonstrated increased activity prosurvival enzyme phosphatidylinositol 3-kinase (PI3K). In fact, cardiomyocytes pretreated exposed H/R exhibited antiapoptotic changes at least five downstream effectors PI3K, protein kinase B (Akt), Bcl-x L /Bcl-2-associated death promoter, caspases-9 -3 activities, expression X-linked inhibitor apoptosis, compared vehicle-treated controls. The PI3K/Akt is one strongest intracellular signaling systems. Our studies show regulate multiple molecular this pathway. Understanding targets EET-mediated protection will promote development these fatty as therapeutic agents against cardiac ischemia-reperfusion.