PARP-2 Regulates SIRT1 Expression and Whole-Body Energy Expenditure

Bai, Péter; Cantó, Carles; Brunyánszki, Attila; Huber, Aline; Szántó, Magdolna; Cen, Yana; Yamamoto, Hiroyasu; Houten, Sander M.; Kiss, Borbála; Oudart, Hugues; Gergely, Pál; Murcia, Josiane Ménissier‐de; Schreiber, Valérie; Sauve, Anthony A.; Auwerx, Johan

doi:10.1016/j.cmet.2011.03.013

Cited by 230 publications

(368 citation statements)

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“…Recent reports revealed that the depletion of PARP-2 modifies the activity of multiple transcription factors [62][63][64]. In HepG2 cells depleted of PARP-2 by shRNA, we have found the dysregulation of more than 600 genes in microarray experiments (Szántó and Bai, unpublished data) indicating an important role for PARP-2 in the regulation of gene expression.…”

Section: Parp-2 In the Regulation Of Gene Expressionmentioning

confidence: 58%

“…PARP-2 serves as a negative regulator of SIRT1 expression, as the absence of PARP-2 induces SIRT1 expression and results in higher SIRT1 activity [33,62]. PARP-2 binds to the murine SIRT1 promoter in a region between -1 --91, which is a highly conserved region among mammals, showing homology even in Xenopus [62].…”

Section: Interaction With Sirt1mentioning

confidence: 99%

“…PARP-2 binds to the murine SIRT1 promoter in a region between -1 --91, which is a highly conserved region among mammals, showing homology even in Xenopus [62]. It must be noted that the ablation, or pharmacological inhibition of PARP-1 also induces SIRT1 activity.…”

Section: Interaction With Sirt1mentioning

confidence: 99%

“…However SIRT1 activation in the absence of PARP-1 depends on enhanced NAD + availability and the ablation of PARP-1 does not alter the activity of the SIRT1 promoter [87]. The action of PARP-2 has been shown in multiple organs and tissues such as skeletal muscle, liver, smooth muscle [33,62] and an unexpected diadvantageous effect has been shown in the pancreas [62]. The depletion of PARP-2 was found not to interfere with SIRT2 or SIRT3 activation [62].…”

Section: Interaction With Sirt1mentioning

confidence: 99%

“…The action of PARP-2 has been shown in multiple organs and tissues such as skeletal muscle, liver, smooth muscle [33,62] and an unexpected diadvantageous effect has been shown in the pancreas [62]. The depletion of PARP-2 was found not to interfere with SIRT2 or SIRT3 activation [62].…”

Section: Interaction With Sirt1mentioning

confidence: 99%

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Poly(ADP-ribose) polymerase-2: emerging transcriptional roles of a DNA-repair protein

Szántó

Brunyánszki

Kiss

et al. 2012

Cell. Mol. Life Sci.

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Abstract:Poly(ADP-ribose) polymerase (PARP)-2 is a nuclear enzyme that belongs to the PARP family and PARP-2 is responsible for 5-15% of total cellular PARP activity. PARP-2 was originally described in connection to DNA repair and in physiological and pathophysiological processes associated with genome maintenance (e.g. centromere and telomere protection, spermiogenesis, thymopoesis, azoospermia and tumorigenesis). Recent reports identified important rearrangements in gene expression upon the knockout of PARP-2. Such rearrangements heavily impact on inflammation and metabolism. Metabolic effects are mediated through modifying PPARg and SIRT1 function. Altered gene expression gives rise to a complex phenotype characterized primarily by enhanced mitochondrial activity that results both in beneficial (loss of fat, enhanced insulin sensitivity) and in disadvantageous (pancreatic beta cell hypofunction upon high fat feeding) consequences. Enhanced mitochondrial biogenesis provides protection in oxidative stress related diseases. Hereby, we review the recent developments in PARP-2 research with special attention to the involvement of PARP-2 in transcriptional and metabolic regulation. We would like to thank the referee for his/her efforts to further improve our manuscript.1. Page 2 -the modifications here are fairly minimalistic and the abbreviations ARTD2 and ARTD1 are not even defined. Powered by Editorial Manager® and Preprint Manager® from Aries Systems Corporationand ARTD1 are not even defined.In the corresponding section we incorporated the basic information on the newly proposed nomenclature in our previous version upon the suggestion of the Reviewer. We agree with the Reviewer that the appearance of the new nomenclature in our manuscript is important. Moreover, in the current version we added ARTD-2 as a keyword to help those future readers that follow the new nomenclature. The fact that ARTD1 is the equivalent of PARP-1 is defined in the chapter "PARP superfamily" second paragraph, first row. We added the abbreviation of ARDT-2 in the last sentence in the first paragraph of the chapter "The PARP superfamily". We think that these are sufficient for the understanding of the position of PARP-2 in the PARP/ARTD superfamily.We would like to note here, that the proposed new nomenclature did not gain ground in the scientific community yet. There are only 3 relevant papers on Medline for the keyword ARTD1, ARTD2 or ARTD (since 2010, the publication of the paper by In summary, we are confident that our review sufficiently takes the new nomenclature into consideration despite of the fact that it is not yet accepted by the scientific community. Sequence homology modeling was carried out by Ame and co-workers (Ame et al. Bioessays. 26:882-893. 2004). They classified sequences as PARPs on the basis of sequence homology, therefore sequence homology does exist. However, mutation(s) in a sequence does not necessarily mean that sequence homology is lost. In the incriminated text, mutations mean rather point mutations that aff...

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Section: Parp-2 In the Regulation Of Gene Expressionmentioning

confidence: 58%

Section: Interaction With Sirt1mentioning

confidence: 99%

Section: Interaction With Sirt1mentioning

confidence: 99%

Section: Interaction With Sirt1mentioning

confidence: 99%

Section: Interaction With Sirt1mentioning

confidence: 99%

See 3 more Smart Citations

Poly(ADP-ribose) polymerase-2: emerging transcriptional roles of a DNA-repair protein

Szántó

Brunyánszki

Kiss

et al. 2012

Cell. Mol. Life Sci.

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Spotlights on Lipid Science from the 36th FEBS Congress, June 25–30, 2011, Torino, Italy

Fabiani

2011

Euro J Lipid Sci & Tech

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Poly (ADP-ribose) polymerase-1 is a key mediator of liver inflammation and fibrosis

et al. 2014

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Poly (ADP-ribose) polymerase 1 (PARP-1) is a constitutive enzyme, the major isoform of PARP family, which is involved in the regulation of DNA repair, cell death, metabolism, and inflammatory responses. Pharmacological inhibitors of PARP provide significant therapeutic benefits in various preclinical disease models associated with tissue injury and inflammation. However, our understanding the role of PARP activation in the pathophysiology of liver inflammation and fibrosis is limited. In this study we have investigated the role of PARP-1 in the liver inflammation and fibrosis using acute and chronic models of CCl4-induced liver injury and fibrosis, a model of bile duct ligation (BDL)-induced hepatic fibrosis in vivo, and isolated liver-derived cells ex vivo. Pharmacological inhibition of PARP with structurally distinct inhibitors or genetic deletion of PARP-1 markedly attenuated CCl4-induced hepatic cell death, inflammation, and fibrosis. Interestingly, the chronic CCl4-induced liver injury was also characterized by mitochondrial dysfunction and dysregulation of numerous genes involved in metabolism. Most of these pathological changes were attenuated by PARP inhibitors. PARP inhibition not only prevented CCl4-induced chronic liver inflammation and fibrosis, but was also able to reverse these pathological processes. PARP inhibitors also attenuated the development of BDL-induced hepatic fibrosis in mice. In liver biopsies of subjects with alcoholic or hepatitis B-induced cirrhosis, increased nitrative stress and PARP activation was noted. These results, taken together, suggest that the reactive oxygen/nitrogen species-PARP pathway plays a pathogenetic role in the development of liver inflammation, metabolism and fibrosis. Several PARP inhibitors are currently in clinical trials for oncological indications. The current results indicate that liver inflammation and liver fibrosis may be additional clinical indications where PARP inhibition may be of translational potential.

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PARP-2 Regulates SIRT1 Expression and Whole-Body Energy Expenditure

Cited by 230 publications

References 39 publications

Poly(ADP-ribose) polymerase-2: emerging transcriptional roles of a DNA-repair protein

Poly(ADP-ribose) polymerase-2: emerging transcriptional roles of a DNA-repair protein

Spotlights on Lipid Science from the 36th FEBS Congress, June 25–30, 2011, Torino, Italy

Poly (ADP-ribose) polymerase-1 is a key mediator of liver inflammation and fibrosis

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