Poly(ADP-ribose) polymerase activity in intact or permeabilized leukocytes from mammalian species of different longevity

Bürkle, Alexander; Müller, Marcus; Wolf, Ivo; Küpper, Jan-Heiner

doi:10.1007/978-1-4615-2614-8_11

Cited by 10 publications

(5 citation statements)

References 24 publications

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“…16 PARP activity is positively correlated with speciesspecific life span in mammalian species. 17,18,19 A (gt)n repeat polymorphism lies in exon 1. 20 The known six alleles, designated according to size (85 bp-99 bp size range), show bimodal frequency distribution, with peaks at 85 bp and 93 bp alleles.…”

Section: Introductionmentioning

confidence: 99%

Gene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2)

et al. 1998

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The possibility that four loci (REN, THO, PARP, SOD2) are associated with longevity was explored by comparing the genotypic pools of subjects older than 100 years with those of younger subjects matched for sex and geographic area (northern and southern Italy). The markers (all located within the respective gene) were HUMREN4; HUMTHO1; HUMPARP (gt)845nt; SOD2(C/T)401nt. In order to reduce the number of genotypes, multiallelic polymorphisms were recoded as diallelic according to allele size and frequency patterns (small: S, and large: L, alleles). A significant loss of LL homozygous genotypes was found at the THO locus in male but not in female centenarians with respect to matched controls. On the other hand no significant difference was found between case/control genotypic frequencies at REN, PARP, SOD2 loci. The latter loci therefore do not affect inter-individual variability in life expectancy (at least in terms of qualitative variants associated with the tested markers). However, the data is consistent with an association between the THO locus and longevity.

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Section: Introductionmentioning

confidence: 99%

Gene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2)

et al. 1998

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“…There are two forms of ADPRT/PARP-1 activity: (1) the constitutive level, associated with normal cellular processes; and (2) the induced level in response to DNA damage [Pero et al, 1985]. Several previous studies reported a positive correlation between its enzyme activity and the species' life span [Pero et al, 1985;Grube and Burkle, 1992;Burkle et al, 1994]. The mRNA levels and enzyme activities were higher in younger than in older subjects [Muiras et al, 1998;Burkle, 2000;Ly et al, 2000], suggesting that poly(ADPribosyl)ation plays a role in aging.…”

Section: Adprt/parp-1 In Agingmentioning

confidence: 97%

“…Cellular ADPRT/PARP-1 may slow the rate of genomic instability resulting from constant exposure to endogenous and exogenous DNA-damaging agents, thereby affecting aging [Burkle et al, 1994;2001;Kapahi et al, 1999]. There are two forms of ADPRT/PARP-1 activity: (1) the constitutive level, associated with normal cellular processes; and (2) the induced level in response to DNA damage [Pero et al, 1985].…”

Section: Adprt/parp-1 In Agingmentioning

confidence: 99%

The Genetic Regulation of ADPRT/PARP-1 in Aging and Cancer Susceptibility

Lockett¹,

Snowhite²,

Hu³

2005

CPG

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The ADP-ribosyltransferase (ADPRT) gene encodes the poly(ADP-ribose)polymerase-1 (PARP-1) enzyme, which plays critical roles in DNA-damage signaling and repair, cell death, maintenance of genomic stability, and carcinogenesis. It may also serve as a potential target for cancer therapy. In this review, we evaluate findings from animal model systems and molecular epidemiological studies to demonstrate the potential role of ADPRT/PARP-1 in aging and carcinogenesis. With increasing interest in associating human cancer risk with single nucleotide polymorphisms (SNPs) and/or dysfunction of ADPRT/PARP-1, several important technical challenges will need to be overcome. These challenges include developing specific functional assays, selecting SNPs with potential functional impact, and exploring statistical methods for gene-gene and gene-environmental interactions. Therefore, this review also highlights strategies to evaluate the functional significance of ADPRT/PARP-1 SNPs in human cancer risk assessment. In summary, dysfunction of PARP-1 may play a critical role in abnormal cellular functions; its molecular mechanism in aging and cancer susceptibility is an issue which needs urgently to be elucidated.

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“…More recently PARP gene expression was studied and demonstrated to be associated to genetic instability in human breast cancer (Bieche et al, 1996). The activity of PARP was shown to positively correlate with species-specific life span of mammals (Burkle et al, 1994). It is known that telomeres shorten with age and this may influence genetic instability (Murnane, 1996), although the potential role of PARP activity in these phenomena remains to be elucidated.…”

mentioning

confidence: 99%

“…Among these are nucleosomal core histones, histone HI, HMG proteins, topoisomerases I and II and PARP itself (Braz and Lechner, 1986; Althaus, 1987). The catalytic activity of PARP is strongly dependent on the presence of DNA strand breaks, which represent the sites for the enzyme recognition (Gradwohl et al, 1990;Ikejima et al, 1990;Molinete et al, 1993;Burkle et al, 1994;Panzeter et al, 1994). The stimulation of PARP by reactive oxygen species has been demonstrated Heller et al, 1995;Crist6vao and Rueff, 1996).…”

mentioning

confidence: 99%

Absence of stimulation of poly(ADP-ribose) polymerase activity in patients predisposed to colon cancer

Cristóvão

Lechner²,

Fidalgo³

et al. 1998

Br J Cancer

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Absence of stimulation of poly(ADPmribose) polymerase activity in patients predisposed to colon cancer L Crist6vdo1, MC Lechner2, P Fidalgo3, CN Leitao3, FC Mira3 and J Rueff1 'Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Rua da Junqueira, 96, P-1300 Lisbon, Portugal; 2Gulbenkian Institute of Sciences, Laboratory of Biochemistry, Oeiras, Rua da Quinta Grande, Apartado 14, P-2781 Oeiras, Portugal; 3Portuguese Institute of Oncology, Service of Gastroenterology, Rua Prof. Lima Basto P-1070 Lisbon, Portugal Summary Poly(ADP-ribose)polymerase (PARP) has been implicated in DNA repair mechanisms and the associated activity shown to markedly increase after DNA damage in carcinogen-treated cells. A defective DNA repair has been associated to the aetiology of human cancers. In order to assess the potential role of this enzyme in cellular response to DNA damage by y-radiation, we studied the activity of PARP in patients with familial adenomatous polyposis (FAP). We compared poly(ADP-ribose)polymerase activity by the rate of incorporation of radioactivity from [3H]adenine-NAD+ into acid-insoluble material in permeabilized leucocytes from FAP patients and healthy volunteers. Concomitantly, the intracellular levels of NAD+ -the substrate for the PARP -and the reduced counterpart NADH were determined using an enzymatic cycling assay 30 min after [60Co] y-ray cells irradiation. Our results demonstrate that a marked stimulation of PARP activity is produced upon radiation of the cells from healthy subjects but not in the FAP leucocytes, which concomitantly show a marked decrease in total NAD+/NADH content. Our observations point to a role of PARP in the repair of the y-radiation-induced DNA lesions through a mechanism that is impaired in the cells from FAP patients genetically predisposed to colon cancer. The differences observed in PARP activation by yradiation in patients and healthy individuals could reflect the importance of PARP activity dependent on treatment with y-rays. The absence of this response in FAP patients would seem to suggest a possible defect in the role of PARP in radiation-induced DNA repair in this cancerprone disease.Keywords: poly(ADP-ribose)polymerase; familial adenomatous polyposis; radiation; DNA repair Poly(ADP-ribose)polymerase (PARP, EC 2.4.2.30) is a chromatinassociated enzyme that catalyses the transfer of the ADP-ribosyl moiety from NAD+ into various acceptor proteins (Chambon et al, 1966;Nishizuka et al, 1968). Among these are nucleosomal core histones, histone HI, HMG proteins, topoisomerases I and II and PARP itself (Braz and Lechner, 1986; Althaus, 1987). The catalytic activity of PARP is strongly dependent on the presence of DNA strand breaks, which represent the sites for the enzyme recognition (Gradwohl et al, 1990;Ikejima et al, 1990;Molinete et al, 1993;Burkle et al, 1994;Panzeter et al, 1994). The stimulation of PARP by reactive oxygen species has been demonstrated Heller et al, 1995;Crist6vao and Rueff, 1996).The precise role of PARP in DNA repair ...

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Poly(ADP-ribose) polymerase activity in intact or permeabilized leukocytes from mammalian species of different longevity

Cited by 10 publications

References 24 publications

Gene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2)

Gene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2)

The Genetic Regulation of ADPRT/PARP-1 in Aging and Cancer Susceptibility

Absence of stimulation of poly(ADP-ribose) polymerase activity in patients predisposed to colon cancer

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