| First Author | Bai P | Year | 2011 |
| Journal | Cell Metab | Volume | 13 |
| Issue | 4 | Pages | 461-468 |
| PubMed ID | 21459330 | Mgi Jnum | J:172241 |
| Mgi Id | MGI:5005032 | Doi | 10.1016/j.cmet.2011.03.004 |
| Citation | Bai P, et al. (2011) PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab 13(4):461-8 |
| abstractText | SIRT1 regulates energy homeostasis by controlling the acetylation status and activity of a number of enzymes and transcriptional regulators. The fact that NAD(+) levels control SIRT1 activity confers a hypothetical basis for the design of new strategies to activate SIRT1 by increasing NAD(+) availability. Here we show that the deletion of the poly(ADP-ribose) polymerase-1 (PARP-1) gene, encoding a major NAD(+)-consuming enzyme, increases NAD(+) content and SIRT1 activity in brown adipose tissue and muscle. PARP-1(-/-) mice phenocopied many aspects of SIRT1 activation, such as a higher mitochondrial content, increased energy expenditure, and protection against metabolic disease. Also, the pharmacologic inhibition of PARP in vitro and in vivo increased NAD(+) content and SIRT1 activity and enhanced oxidative metabolism. These data show how PARP-1 inhibition has strong metabolic implications through the modulation of SIRT1 activity, a property that could be useful in the management not only of metabolic diseases, but also of cancer. |
