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Preconditioning by 17-estradiol in isolated rat heart depends on PI3-K/PKB pathway, PKC, and ROS

¹Department of Medical Physiology and ²Department of Biochemistry, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Tromsø; and ³Department of Biomedicine, Section for Physiology, Faculty of Medicine, University of Bergen, Bergen, Norway

Submitted 4 November 2005 ; accepted in final form 25 April 2006

To study the cell signaling events leading to 17-estradiol (E₂)-induced acute cardioprotection, we subjected isolated rat hearts to three 5-min cycles of 10 µM E₂ before 30 min of regional ischemia, followed by 2 h of reperfusion. Protection was judged by changes in infarct size in percentage of risk zone volume. To test the importance of phosphoinositide 3-kinase (PI3-K), protein kinase C (PKC), or reactive oxygen species (ROS) in E₂-induced protection, we combined wortmannin (1 µM), chelerythrine (2 µM), and 2-mercaptopropionylglycine (300 µM), respectively, with E₂ exposure. Changes in phosphorylation of protein kinase B (PKB) and selected PKC isoforms were tested by immunoblotting of total lysates and subcellular fractions, along with assessment of PKC translocation from soluble to membrane fraction of heart tissue homogenates. Intracellular ROS levels induced by E₂ preconditioning were investigated. E₂ preconditioning led to significant reduction in infarct size from 31.8 ± 5.3 to 20.2 ± 2.6% in male hearts and from 42.7 ± 4.7 to 17.1 ± 3.4% in female hearts (P < 0.05). Protection was abolished by wortmannin (30.0 ± 3.2%), chelerythrine (45.1 ± 4.4%), and 2-mercaptopropionylglycine (36.8 ± 4.7%). E₂ preconditioning induced phosphorylation of PKB, PKC, and PKC and membrane translocation of PKC and PKC. Intracellular ROS levels were found elevated after transient treatment with hormone. Therefore, our data demonstrate the ability of E₂ to induce preconditioning-like cardioprotection via cell signaling events shared by classic ischemic preconditioning.

phosphoinositide 3-kinase; protein kinase B; protein kinase C; reactive oxygen species

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