Adora2b-elicited Per2 stabilization promotes a HIF-dependent metabolic switch crucial for myocardial adaptation to ischemia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-05

AUTHORS

Tobias Eckle, 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. More... »

PAGES

774

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.2728

DOI

http://dx.doi.org/10.1038/nm.2728

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1047916087

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22504483


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