CREB activation and ischaemic preconditioning

Cardiovascular Drugs and Therapy
E MaraisA Lochner

Abstract

Previous studies from our laboratory showed that activation of p38 MAPK is one of the triggers of ischaemic preconditioning. The signalling events downstream of p38 MAPK and their links to the putative final effectors of preconditioning are not clear. The cAMP responsive element-binding protein (CREB) is also phosphorylated by exposure to short episodes of ischaemia/reperfusion, suggesting a triggering action. The aim of this study was to systematically investigate (1) the signalling pathways leading to CREB phosphorylation during an ischaemic or beta-adrenergic preconditioning protocol (2) changes in CREB phosphorylation during sustained ischaemia and their significance in ischaemia/reperfusion injury. The isolated perfused working rat heart was preconditioned by 1 x 5 min global ischaemia or 3 x 5 min global ischaemia and freeze-clamped. Drugs to manipulate CREB activation were added 5 min before onset of ischaemia. Non-preconditioned and preconditioned hearts were subjected to 25 min global or 35 min regional ischaemia, followed by 30 min reperfusion. Infarct sizes were determined using tetrazolium staining. Phosphorylation of CREB was determined by Western blots. Exposure of hearts to 5 min global ischaemia followed by repe...Continue Reading

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Citations

Jul 20, 2010·Cardiovascular Drugs and Therapy·Yumei YeYochai Birnbaum
Sep 19, 2012·Metabolic Syndrome and Related Disorders·Yochai BirnbaumMandeep Bajaj
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Oct 30, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Yumei YeYochai Birnbaum
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