| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2048511 | FEBS Letters | 2012 | 9 Pages |
The discovery of sirtuins (SIRT), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, has indicated that intracellular NAD level is crucial for the hypertrophic response of cardiomyocytes. Nicotinamide mononucleotide adenylyltransferase (Nmnat) is a central enzyme in NAD biosynthesis. Here we revealed that Nmnat2 protein expression and enzyme activity were down-regulated during cardiac hypertrophy. In neonatal rat cardiomyocytes, overexpression of Nmnat2 but not its catalytically inactive mutant blocked angiotensin II (Ang II)-induced cardiac hypertrophy, which was dependent on activation of SIRT6 through maintaining the intracellular NAD level. Our results suggested that modulation of Nmnat2 activity may be beneficial in cardiac hypertrophy.
► We investigated the role of Nmnat2 in cardiac hypertrophy. ► Nmnat2 was decreased in AAC rats and Ang II-induced cardiac hypertrophy. ► Overexpression of wild-type Nmnat2 attenuated Ang II-induced cardiac hypertrophy. ► The anti-hypertrophic effect of Nmnat2 was dependent on activation of SIRT6.
