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Cardioprotective mIGF-1/SIRT1 signaling induces hypertension, leukocytosis and fear response in mice.


ABSTRACT: Locally acting insulin growth factor isoform (mIGF-1) and the NAD+-dependent protein deacetylase SIRT1 are implicated in life and health span. Heart failure is associated with aging and is a major cause of death. mIGF-1 protects the heart from oxidative stresses via SIRT1. SIRT1 subcellular localization and its genomic regulation by mIGF-1 are unknown. We show here that SIRT1 is located in the nuclei of a significant fraction of cardiomyocytes. Using high throughput sequencing approaches in mIGF-1 transgenic mice, we identified new targets of the mIGF-1/SIRT1 signaling. In addition to its potent cardioprotective properties, cardiac-restricted mIGF-1 transgene induced systemic changes such as high blood pressure, leukocytosis and an enhanced fear response, in a SIRT1-dependent manner. Cardiac mIGF-1/ SIRT1 signaling may thus modulate disparate systemic functions.

SUBMITTER: Bolasco G 

PROVIDER: S-EPMC3409677 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Cardioprotective mIGF-1/SIRT1 signaling induces hypertension, leukocytosis and fear response in mice.

Bolasco Giulia G   Calogero Raffaele R   Carrara Matteo M   Banchaabouchi Mumna Al MA   Bilbao Daniel D   Mazzoccoli Gianluigi G   Vinciguerra Manlio M  

Aging 20120601 6


Locally acting insulin growth factor isoform (mIGF-1) and the NAD+-dependent protein deacetylase SIRT1 are implicated in life and health span. Heart failure is associated with aging and is a major cause of death. mIGF-1 protects the heart from oxidative stresses via SIRT1. SIRT1 subcellular localization and its genomic regulation by mIGF-1 are unknown. We show here that SIRT1 is located in the nuclei of a significant fraction of cardiomyocytes. Using high throughput sequencing approaches in mIGF  ...[more]

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