Endogenous and exogenous nitric oxide enhance the DNA strand scission induced by tert-butylhydroperoxide in PC12 cells via peroxynitrite-dependent and independent mechanisms, respectively

Piero Sestili, Emilio Clementi, Andrea Guidarelli, Clara Sciorati, Orazio Cantoni

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

A short-term exposure to tert-butylhydroperoxide (tB-OOH) promoted a concentration-dependent formation of DNA single-strand breaks in PC12 cells. These events were paralleled by an increase in the cytosolic concentration of Ca2+ that was in part cleared by the mitochondria. Unlike the extent of Ca2+ mobilization and/or mitochondrial Ca2+ clearance, the DNA strand scission evoked by the hydroperoxide was markedly reduced by the nitric oxide (NO) scavenger 2-phenyl-4,4,5,5-tetramethylimidazolin-1-oxyl-3-oxide (PTIO) or by the NO synthase inhibitor N-nitro-L-arginine methylester (L-NAME). Inhibitors of electron transport (rotenone and myxothiazol), ruthenium red (RR, a polycation which inhibits the calcium uniporter of mitochondria), or peroxynitrite scavengers (Trolox and L-methionine) were as effective as PTIO or L-NAME in inhibiting the DNA-damaging response mediated by tB-OOH. Rotenone, RR or peroxynitrite scavengers did not further reduce the residual DNA cleavage observed following treatment with tB-OOH in L-NAME-supplemented cells. Exogenous NO also increased the DNA damage caused by tB-OOH in L-NAME-supplemented cells and this response was blunted by RR or by inhibitors of electron transport but was insensitive to peroxynitrite scavengers. We conclude that both endogenous and exogenous NO enhance the DNA cleavage generated by tB-OOH in PC12 cells. However, only endogenous NO set the bases for an involvement of peroxynitrite in this DNA-damaging response.

Original languageEnglish
Pages (from-to)145-154
Number of pages10
JournalEuropean Journal of Neuroscience
Volume12
Issue number1
DOIs
Publication statusPublished - 2000

Fingerprint

tert-Butylhydroperoxide
Peroxynitrous Acid
PC12 Cells
NG-Nitroarginine Methyl Ester
Nitric Oxide
Rotenone
DNA Cleavage
DNA
Electron Transport
Mitochondria
Single-Stranded DNA Breaks
Ruthenium Red
Nitric Oxide Synthase
Methionine
Hydrogen Peroxide
DNA Damage
Arginine
2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide

Keywords

  • Calcium ions
  • DNA damage
  • Mitochondria
  • Neuronal cells
  • Short chain hydroperoxides

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Endogenous and exogenous nitric oxide enhance the DNA strand scission induced by tert-butylhydroperoxide in PC12 cells via peroxynitrite-dependent and independent mechanisms, respectively. / Sestili, Piero; Clementi, Emilio; Guidarelli, Andrea; Sciorati, Clara; Cantoni, Orazio.

In: European Journal of Neuroscience, Vol. 12, No. 1, 2000, p. 145-154.

Research output: Contribution to journalArticle

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