| Literature DB >> 22504483 |
Tobias Eckle1, Katherine Hartmann, Stephanie Bonney, Susan Reithel, Michel Mittelbronn, Lori A Walker, Brian D Lowes, Jun Han, Christoph H Borchers, Peter M Buttrick, Douglas J Kominsky, Sean P Colgan, Holger K Eltzschig.
Abstract
Adenosine signaling has been implicated in cardiac adaptation to limited oxygen availability. In a wide search for adenosine receptor A2b (Adora2b)-elicited cardioadaptive responses, we identified the circadian rhythm protein period 2 (Per2) as an Adora2b target. Adora2b signaling led to Per2 stabilization during myocardial ischemia, and in this setting, Per2(-/-) mice had larger infarct sizes compared to wild-type mice and loss of the cardioprotection conferred by ischemic preconditioning. Metabolic studies uncovered a limited ability of ischemic hearts in Per2(-/-) mice to use carbohydrates for oxygen-efficient glycolysis. This impairment was caused by a failure to stabilize hypoxia-inducible factor-1α (Hif-1α). Moreover, stabilization of Per2 in the heart by exposing mice to intense light resulted in the transcriptional induction of glycolytic enzymes and Per2-dependent cardioprotection from ischemia. Together, these studies identify adenosine-elicited stabilization of Per2 in the control of HIF-dependent cardiac metabolism and ischemia tolerance and implicate Per2 stabilization as a potential new strategy for treating myocardial ischemia.Entities:
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Year: 2012 PMID： 22504483 PMCID： PMC3378044 DOI： 10.1038/nm.2728
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440