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Aging-associated Alteration in the Cardiac MIF-AMPK Cascade in Response to Ischemic Stress

Heng Ma¹, Jingying Wang¹, Erin Lane¹, Lin Leng², Wenkui Wang², Jun Ren³, Richard Bucala⁴ & Ji Li³

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1. Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming
2. Department of Medicine, Yale University School of Medicine
3. School of Pharmacy, University of Wyoming
4. Rheumatology and Pathology, Yale University School of Medicine

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Document Type:

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Date:

Received 04 November 2008 17:57 UTC; Posted 06 November 2008

Subjects:

Molecular Cell Biology, Pharmacology

Tags:

• Aging
• myocardial damage
• ischemia
• AMPK
• Cardiac
• MIF
• hypoxia

Abstract:

An important role for a macrophage migration inhibitory factor (MIF)-AMP-activated protein kinase (AMPK) signaling pathway in ameliorating myocardial damage following ischemia/reperfusion has been described. An aging-associated reduction in AMPK activity may be associated with a decline in the ability of cardiac cells to activate the MIF-AMPK cascade, thereby resulting in reduced tolerance to ischemic insults. To test this hypothesis, in vivo regional ischemia was induced by occlusion of the left anterior descending (LAD) coronary artery in young (4-6 months) and aged (24-26 months) mice. The ischemic AMPK activation response was impaired in aged hearts compared to young ones (p<0.05). Ischemia-induced AMPK activation in MIF knock out (MIF KO) hearts was blunted, leading to greater contractile dysfunction of MIF KO cardiomyocytes during hypoxia than that of wild type (WT) cardiomyocytes. Finally exogenous recombinant MIF significantly reversed the contractile dysfunction of aged cardiomyocytes in response to hypoxia. We conclude that an aging-associated reduction in ischemic AMPK activation contributes to ischemic intolerance in aged hearts.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Ma, Heng, Wang, Jingying, Lane, Erin, Leng, Lin, Wang, Wenkui, Ren, Jun, Bucala, Richard, and Li, Ji. Aging-associated Alteration in the Cardiac MIF-AMPK Cascade in Response to Ischemic Stress. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.2466.1> (2008)

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Version number	Document title	Date
v2	Posted 12 June 2009

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