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Peroxynitrite and hydrogen peroxide induced cell death in the NSC34 neuroblastoma x spinal cord cell line: role of poly (ADP-ribose) polymerase.
J Neurochem. 1998 Feb; 70(2):501-8.JN

Abstract

The reaction of superoxide and nitric oxide results in the formation of peroxynitrite, a long lived and highly reactive oxidant species. It has been suggested that the formation of peroxynitrite in vivo may contribute to cell death in some neurological conditions. We have examined the effect of peroxynitrite on cell death in the NSC34 spinal cord cell line. A brief (30 min) exposure to either peroxynitrite or hydrogen peroxide caused delayed cell death with an EC50 for both of approximately 1 mM. Cell death was prevented by the RNA synthesis inhibitor actinomycin D and included DNA damage as an early event. We sought to clarify the potential role of the DNA binding enzyme poly(ADP-ribose) polymerase (PARP) in cell death in these cells. Several PARP inhibitors [benzamide, 3-aminobenzamide, nicotinamide, and 6(5H)-phenanthridinone] prevented cell death, but the inactive analogue benzoic acid did not. However, there was no evidence of cleavage of PARP, which occurs in apoptosis via the activation of the caspase CPP32. Therefore, we suggest that PARP contributes to neuronal injury as an early event, probably by lethal NAD depletion, without any requirement for proteolytic cleavage.

Authors+Show Affiliations

Newcastle General Hospital, and Department of Neurology, University of Newcastle, Newcastle upon Tyne, England, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9453543

Citation

Cookson, M R., et al. "Peroxynitrite and Hydrogen Peroxide Induced Cell Death in the NSC34 Neuroblastoma X Spinal Cord Cell Line: Role of Poly (ADP-ribose) Polymerase." Journal of Neurochemistry, vol. 70, no. 2, 1998, pp. 501-8.
Cookson MR, Ince PG, Shaw PJ. Peroxynitrite and hydrogen peroxide induced cell death in the NSC34 neuroblastoma x spinal cord cell line: role of poly (ADP-ribose) polymerase. J Neurochem. 1998;70(2):501-8.
Cookson, M. R., Ince, P. G., & Shaw, P. J. (1998). Peroxynitrite and hydrogen peroxide induced cell death in the NSC34 neuroblastoma x spinal cord cell line: role of poly (ADP-ribose) polymerase. Journal of Neurochemistry, 70(2), 501-8.
Cookson MR, Ince PG, Shaw PJ. Peroxynitrite and Hydrogen Peroxide Induced Cell Death in the NSC34 Neuroblastoma X Spinal Cord Cell Line: Role of Poly (ADP-ribose) Polymerase. J Neurochem. 1998;70(2):501-8. PubMed PMID: 9453543.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peroxynitrite and hydrogen peroxide induced cell death in the NSC34 neuroblastoma x spinal cord cell line: role of poly (ADP-ribose) polymerase. AU - Cookson,M R, AU - Ince,P G, AU - Shaw,P J, PY - 1998/2/7/pubmed PY - 1998/2/7/medline PY - 1998/2/7/entrez SP - 501 EP - 8 JF - Journal of neurochemistry JO - J Neurochem VL - 70 IS - 2 N2 - The reaction of superoxide and nitric oxide results in the formation of peroxynitrite, a long lived and highly reactive oxidant species. It has been suggested that the formation of peroxynitrite in vivo may contribute to cell death in some neurological conditions. We have examined the effect of peroxynitrite on cell death in the NSC34 spinal cord cell line. A brief (30 min) exposure to either peroxynitrite or hydrogen peroxide caused delayed cell death with an EC50 for both of approximately 1 mM. Cell death was prevented by the RNA synthesis inhibitor actinomycin D and included DNA damage as an early event. We sought to clarify the potential role of the DNA binding enzyme poly(ADP-ribose) polymerase (PARP) in cell death in these cells. Several PARP inhibitors [benzamide, 3-aminobenzamide, nicotinamide, and 6(5H)-phenanthridinone] prevented cell death, but the inactive analogue benzoic acid did not. However, there was no evidence of cleavage of PARP, which occurs in apoptosis via the activation of the caspase CPP32. Therefore, we suggest that PARP contributes to neuronal injury as an early event, probably by lethal NAD depletion, without any requirement for proteolytic cleavage. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/9453543/Peroxynitrite_and_hydrogen_peroxide_induced_cell_death_in_the_NSC34_neuroblastoma_x_spinal_cord_cell_line:_role_of_poly__ADP_ribose__polymerase_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=1998&volume=70&issue=2&spage=501 DB - PRIME DP - Unbound Medicine ER -