Publikation: l-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ationResponse to Ionizing Radiation
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DNA strand breaks induced by alkylating agents, oxidants, or ionizingradiation trigger the covalent modification of nuclear proteins withpoly(ADP-ribose), which is catalyzed for the most part by poly(ADP-ribose)polymerase-1 and plays a role in DNA base-excision repair.Poly(ADP-ribosyl)ation capacity of mononuclear blood cells correlatespositively with life span of mammalian species. Here, we show that l-selegiline, an anti-Parkinson drug with neuroprotective activityand life span-extending effect in laboratory animals, can potentiate γ-radiation-induced poly(ADP-ribose) formation in intact cells. COR4hamster cells were incubated with l-selegiline (50 nM) for varioustime periods, followed by γ-irradiation (45 Gy). Quantification ofcellular poly(ADP-ribose) levels at 10 min after starting the irradiationrevealed significant increases (up to 1.8-fold) in cells preincubated with thedrug for 8 h to 7 days compared with drug-free irradiated controls. There wasno selegiline-induced change in poly(ADP-ribose) levels of unirradiated cellsnor in basal or radiation-induced DNA strand breaks, respectively.Surprisingly, poly(ADP-ribose) polymerase-1 protein was down-regulated by l-selegiline treatment. Addition of l-selegiline topurified poly(ADP-ribose) polymerase-1 did not alter enzymatic activity. Inconclusion, the results of the present study identify a novel intervention topotentiate the cellular poly(ADP-ribosyl)ation response. We hypothesize thatthe effect of l-selegiline is due to modulation of accessoryproteins regulating poly(ADP-ribose) polymerase-1 activity and that increasedcellular poly- (ADP-ribosyl)ation capacity may contribute to theneuroprotective potential and/or life span extension afforded by l-selegiline.
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BRABECK, Christine, Ragen PFEIFFER, Alan LEAKE, Sascha BENEKE, Ralph MEYER, Alexander BÜRKLE, 2003. l-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ationResponse to Ionizing Radiation. In: Journal of Pharmacology and Experimental Therapeutics. American Society for Pharmacology and Experimental Therapeutics. 2003, 306(3), pp. 973-979. ISSN 0022-3565. eISSN 1521-0103. Available under: doi: 10.1124/jpet.103.051342BibTex
@article{Brabeck2003-09lSele-52313, year={2003}, doi={10.1124/jpet.103.051342}, title={l-Selegiline Potentiates the Cellular Poly(ADP-Ribosyl)ationResponse to Ionizing Radiation}, number={3}, volume={306}, issn={0022-3565}, journal={Journal of Pharmacology and Experimental Therapeutics}, pages={973--979}, author={Brabeck, Christine and Pfeiffer, Ragen and Leake, Alan and Beneke, Sascha and Meyer, Ralph and Bürkle, Alexander} }
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