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Article Dans Une Revue Cell Metab Année : 2011

PARP-1 Inhibition Increases Mitochondrial Metabolism through SIRT1 Activation.

Résumé

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.

Dates et versions

hal-00586349 , version 1 (15-04-2011)

Identifiants

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Péter Bai, Carles Cantó, Hugues Oudart, Attila Brunyánszki, Yana Cen, et al.. PARP-1 Inhibition Increases Mitochondrial Metabolism through SIRT1 Activation.. Cell Metab, 2011, 13 (4), pp.461-468. ⟨10.1016/j.cmet.2011.03.004⟩. ⟨hal-00586349⟩
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