Ex vivo supplementation with nicotinic acid enhances cellular poly(ADP-ribosyl)ation and improves cell viability in human peripheral blood mononuclear cells

Weidele, Kathrin; Kunzmann, Andrea; Schmitz, Maike; Beneke, Sascha; Bürkle, Alexander

Ex vivo supplementation with nicotinic acid enhances cellular poly(ADP-ribosyl)ation and improves cell viability in human peripheral blood mononuclear cells

Dateien

2010_BiochemPharmacol80_1103_Weidele.pdfGröße: 1.07 MBDownloads: 1090

Datum

2010

Autor:innen

Weidele, Kathrin

Kunzmann, Andrea

Schmitz, Maike

Beneke, Sascha

Bürkle, Alexander

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Biochemical Pharmacology. 2010, 80(7), pp. 1103-1112. ISSN 0006-2952. eISSN 1873-2968. Available under: doi: 10.1016/j.bcp.2010.06.010

Zusammenfassung

Poly(ADP-ribosyl)ation is a posttranslational modification of proteins, which is mainly catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1) by using NAD+ as substrate and is directly triggered by DNA strand breaks. Under mild genotoxic stress poly(ADP-ribose) (PAR) formation plays an important role in DNA repair whereas severe genotoxic stress and the ensuing overactivation of PARP-1 induce cellular NAD+ depletion, energy failure and ultimately cell death. We are interested in studying the consequences of moderately enhanced enzymatic activity under conditions of DNA damage. Here we chose supplementation of cells with the NAD+ precursor nicotinic acid (NA) as a strategy. In order to reliably assess PAR accumulation in living cells we first developed a novel, sensitive flow-cytometric method for the rapid analysis of poly(ADP-ribose) accumulation (RAPARA). Our data showed that ex vivo supplementation of human peripheral blood mononuclear cells (PBMC) with low concentrations of NA significantly raised cellular NAD+ levels by 2.1-fold. Upon X-irradiation or exposure to hydrogen peroxide or N-methyl-N′-nitro-N-nitrosoguanidine, PAR accumulation was significantly increased and sustained in NA-supplemented cells. Furthermore, NA-supplemented PBMC displayed significantly higher cell viability due to a lower rate of necrotic cell death. In summary, ex vivo supplementation of human PBMC with NA increases cellular NAD+ levels, boosts the cellular poly(ADP-ribosyl)ation response to genotoxic treatment, and protects from DNA-damage-induced cell death.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

Poly(ADP-ribosyl)ation, PARP-1, NAD+, Necrosis, PBMC

Zitieren

ISO 690

WEIDELE, Kathrin, Andrea KUNZMANN, Maike SCHMITZ, Sascha BENEKE, Alexander BÜRKLE, 2010. Ex vivo supplementation with nicotinic acid enhances cellular poly(ADP-ribosyl)ation and improves cell viability in human peripheral blood mononuclear cells. In: Biochemical Pharmacology. 2010, 80(7), pp. 1103-1112. ISSN 0006-2952. eISSN 1873-2968. Available under: doi: 10.1016/j.bcp.2010.06.010

BibTex

@article{Weidele2010suppl-7711,
  year={2010},
  doi={10.1016/j.bcp.2010.06.010},
  title={Ex vivo supplementation with nicotinic acid enhances cellular poly(ADP-ribosyl)ation and improves cell viability in human peripheral blood mononuclear cells},
  number={7},
  volume={80},
  issn={0006-2952},
  journal={Biochemical Pharmacology},
  pages={1103--1112},
  author={Weidele, Kathrin and Kunzmann, Andrea and Schmitz, Maike and Beneke, Sascha and Bürkle, Alexander}
}

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