| First Author | Vinciguerra M | Year | 2012 |
| Journal | Aging Cell | Volume | 11 |
| Issue | 1 | Pages | 139-49 |
| PubMed ID | 22051242 | Mgi Jnum | J:218881 |
| Mgi Id | MGI:5618614 | Doi | 10.1111/j.1474-9726.2011.00766.x |
| Citation | Vinciguerra M, et al. (2012) mIGF-1/JNK1/SirT1 signaling confers protection against oxidative stress in the heart. Aging Cell 11(1):139-49 |
| abstractText | Oxidative stress contributes to the pathogenesis of aging-associated heart failure. Among various signaling pathways mediating oxidative stress, the NAD(+) -dependent protein deacetylase SirT1 has been implicated in the protection of heart muscle. Expression of a locally acting insulin-like growth factor-1 (IGF-1) propeptide (mIGF-1) helps the heart to recover from infarct and enhances SirT1 expression in cardiomyocytes (CM) in vitro, exerting protection from hypertrophic and oxidative stresses. To study the role of mIGF-1/SirT1 signaling in vivo, we generated cardiac-specific mIGF-1 transgenic mice in which SirT1 was depleted from adult CM in a tamoxifen-inducible and conditional fashion. Analysis of these mice confirmed that mIGF-1-induced SirT1 activity is necessary to protect the heart from paraquat (PQ)-induced oxidative stress and lethality. In cultured CM, mIGF-1 increases SirT1 expression through a c-Jun NH(2)-terminal protein kinase 1 (JNK1)-dependent signaling mechanism. Thus, mIGF-1 protects the heart from oxidative stress via SirT1/JNK1 activity, suggesting new avenues for cardiac therapy during aging and heart failure. |
