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The role of NADPH oxidase and neuronal nitric oxide synthase in zinc-induced poly(ADP-ribose) polymerase activation and cell death in cortical culture.
Exp Neurol. 2002 Oct; 177(2):407-18.EN

Abstract

In the present study, we examined the role and the mechanism of poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) activation in zinc-induced cell death in cortical culture. After brief exposure to 400 microM zinc, cortical cells exhibited DNA fragmentation, increased poly(ADP-ribosyl)ation, and decreased levels of nicotinamide adenine dinucleotide (NAD) and ATP and subsequently underwent cell death. Inhibitors of PARP/PARG attenuated both zinc-induced NAD/ATP depletion and cell death, thereby implicating the PARP/PARG cascade in these processes. The zinc-inducible enzymes NADPH oxidase and neuronal nitric oxide synthase (nNOS) contributed to PARP activation as their inhibitors attenuated zinc-induced poly(ADP-ribosyl)ation. Levels of nitric oxide and nitrites increased following zinc exposure, consistent with NOS activation. In addition, Western blots and RT-PCR analysis revealed that protein and mRNA levels of nNOS specifically increased following zinc exposure in a manner similar to that of NADPH oxidase. The present study demonstrates that induction of NADPH oxidase and nNOS actively contributes to PARP/PARG-mediated NAD/ATP depletion and cell death induced by zinc in cortical culture.

Authors+Show Affiliations

National Creative Research Initiative Center for the Study of CNS Zinc, Department of Neurology, University of Ulsan College of Medicine, Seoul, 138-736, Korea.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12429187

Citation

Kim, Yang-Hee, and Jae-Young Koh. "The Role of NADPH Oxidase and Neuronal Nitric Oxide Synthase in Zinc-induced poly(ADP-ribose) Polymerase Activation and Cell Death in Cortical Culture." Experimental Neurology, vol. 177, no. 2, 2002, pp. 407-18.
Kim YH, Koh JY. The role of NADPH oxidase and neuronal nitric oxide synthase in zinc-induced poly(ADP-ribose) polymerase activation and cell death in cortical culture. Exp Neurol. 2002;177(2):407-18.
Kim, Y. H., & Koh, J. Y. (2002). The role of NADPH oxidase and neuronal nitric oxide synthase in zinc-induced poly(ADP-ribose) polymerase activation and cell death in cortical culture. Experimental Neurology, 177(2), 407-18.
Kim YH, Koh JY. The Role of NADPH Oxidase and Neuronal Nitric Oxide Synthase in Zinc-induced poly(ADP-ribose) Polymerase Activation and Cell Death in Cortical Culture. Exp Neurol. 2002;177(2):407-18. PubMed PMID: 12429187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of NADPH oxidase and neuronal nitric oxide synthase in zinc-induced poly(ADP-ribose) polymerase activation and cell death in cortical culture. AU - Kim,Yang-Hee, AU - Koh,Jae-Young, PY - 2002/11/14/pubmed PY - 2002/11/28/medline PY - 2002/11/14/entrez SP - 407 EP - 18 JF - Experimental neurology JO - Exp Neurol VL - 177 IS - 2 N2 - In the present study, we examined the role and the mechanism of poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) activation in zinc-induced cell death in cortical culture. After brief exposure to 400 microM zinc, cortical cells exhibited DNA fragmentation, increased poly(ADP-ribosyl)ation, and decreased levels of nicotinamide adenine dinucleotide (NAD) and ATP and subsequently underwent cell death. Inhibitors of PARP/PARG attenuated both zinc-induced NAD/ATP depletion and cell death, thereby implicating the PARP/PARG cascade in these processes. The zinc-inducible enzymes NADPH oxidase and neuronal nitric oxide synthase (nNOS) contributed to PARP activation as their inhibitors attenuated zinc-induced poly(ADP-ribosyl)ation. Levels of nitric oxide and nitrites increased following zinc exposure, consistent with NOS activation. In addition, Western blots and RT-PCR analysis revealed that protein and mRNA levels of nNOS specifically increased following zinc exposure in a manner similar to that of NADPH oxidase. The present study demonstrates that induction of NADPH oxidase and nNOS actively contributes to PARP/PARG-mediated NAD/ATP depletion and cell death induced by zinc in cortical culture. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/12429187/The_role_of_NADPH_oxidase_and_neuronal_nitric_oxide_synthase_in_zinc_induced_poly_ADP_ribose__polymerase_activation_and_cell_death_in_cortical_culture_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014488602979902 DB - PRIME DP - Unbound Medicine ER -