2012
DOI: 10.1155/2012/321653
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Pleiotropic Cellular Functions of PARP1 in Longevity and Aging: Genome Maintenance Meets Inflammation

Abstract: Aging is a multifactorial process that depends on diverse molecular and cellular mechanisms, such as genome maintenance and inflammation. The nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP1), which catalyzes the synthesis of the biopolymer poly(ADP-ribose), exhibits an essential role in both processes. On the one hand, PARP1 serves as a genomic caretaker as it participates in chromatin remodelling, DNA repair, telomere maintenance, resolution of replicative stress, and cell cycle control. On the other hand… Show more

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Cited by 106 publications
(81 citation statements)
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References 217 publications
(240 reference statements)
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“…One of these roles includes the activation of the nuclear enzyme poly(ADP-ribose), polymerase (PARP-1), which leads to the production of inflammatory mediators such as iNOS, ICAM-1, and major histocompatibility complex class II. Lack of NO leads to vasodilator dysfunction and promotes endothelial apoptosis, whereas nitrative stress and increased H 2 O 2 levels lead to poly(ADP-ribose) polymerase (PARP)-1 activation, which contributes to NF-B -dependent gene transcription (Ungvari et al, 2010;Mangerich and Burkle, 2012). NF-B, an integral factor in vascular health triad (Donato et al, 2009), is involved in transcriptional activation of pro-inflammatory and pro-oxidative genes leading to impaired vascular function.…”
Section: Nuclear Factor-kappa Bmentioning
confidence: 99%
“…One of these roles includes the activation of the nuclear enzyme poly(ADP-ribose), polymerase (PARP-1), which leads to the production of inflammatory mediators such as iNOS, ICAM-1, and major histocompatibility complex class II. Lack of NO leads to vasodilator dysfunction and promotes endothelial apoptosis, whereas nitrative stress and increased H 2 O 2 levels lead to poly(ADP-ribose) polymerase (PARP)-1 activation, which contributes to NF-B -dependent gene transcription (Ungvari et al, 2010;Mangerich and Burkle, 2012). NF-B, an integral factor in vascular health triad (Donato et al, 2009), is involved in transcriptional activation of pro-inflammatory and pro-oxidative genes leading to impaired vascular function.…”
Section: Nuclear Factor-kappa Bmentioning
confidence: 99%
“…PARP1 [the poly (ADP-ribose) polymerase 1 gene] is a gene that has been linked to longevity in mammals [17]. PARP1 has a key role in regulating cell-cycle and DNA repair mechanisms.…”
Section: Histone Modificationsmentioning
confidence: 99%
“…PARP1 is a ubiquitously expressed protein playing key roles in genomic maintenance, chromatin organization, transcription, and the regulation of cell death (Mangerich and Bürkle, 2012;Rouleau et al, 2010). PARP1 binds to DNA strand breaks and by using NAD + as a substrate, catalyzes the formation of homopolymeric branched chains of poly(ADP ribose) (PAR) of different length that are covalently bound to "acceptor" proteins at glutamate, aspartate or lysine residues.…”
Section: Introductionmentioning
confidence: 99%