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Peroxynitrite and Hydrogen Peroxide Induced Cell Death in the NSC34 Neuroblastoma × Spinal Cord Cell Line: Role of Poly(ADP‐Ribose) Polymerase
Author(s) -
Cookson Mark R.,
Ince Paul G.,
Shaw Pamela J.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70020501.x
Subject(s) - peroxynitrite , poly adp ribose polymerase , programmed cell death , chemistry , apoptosis , nad+ kinase , microbiology and biotechnology , peroxynitrous acid , nitric oxide , biochemistry , superoxide , polymerase , biology , enzyme , organic chemistry
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 EC 50 for both of ∼1 m M . 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(5 H )‐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.