| Registro completo |
| Provedor de dados: |
Nature Precedings
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| País: |
United Kingdom
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| Título: |
Aging-associated Alteration in the Cardiac MIF-AMPK Cascade in Response to Ischemic Stress
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| Autores: |
Heng Ma
Jingying Wang
Erin Lane
Lin Leng
Wenkui Wang
Jun Ren
Richard Bucala
Ji Li
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| Data: |
2008-11-04
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| Ano: |
2008
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| Palavras-chave: |
Molecular Cell Biology
Pharmacology
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| Resumo: |
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<0.01). Notably, cardiac MIF expression in aged hearts was lower than in young hearts (p<0.01). Dual staining data clearly demonstrated larger infarct size in aged hearts following ischemia and reperfusion compared to young hearts (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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| Tipo: |
Manuscript
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| Identificador: |
http://precedings.nature.com/documents/2466/version/1
oai:nature.com:10101/npre.2008.2466.1
http://hdl.handle.net/10101/npre.2008.2466.1
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| Fonte: |
Nature Precedings
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| Direitos: |
Creative Commons Attribution 3.0 License
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