Role of peroxynitrite in the protein oxidation and apoptotic dna fragmentation in vascular smooth muscle cells stimulated with bacterial lipopolysaccharide and interferon-γ

Michael O'Connor, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

In the present study, we investigated the role of endogenous and exogenous peroxynitrite in the process of DNA fragmentation and protein oxidation in cultured rat aortic smooth muscle cells. Peroxynitrite induced DNA fragmentation over a 24 hr period. The effect of peroxynitrite was unaffected by pretreatment with 3-aminobenzamide, an inhibitor of the nuclear enzyme poly (ADP-ribose) synthetase (PARS). Stimulation of the smooth muscle cells with bacterial lipopolysaccharide and interferon-γ produced nitric oxide and peroxynitrite, and resulted in a significant degree of apoptotic DNA fragmentation. The nitric oxide synthase inhibitor NG-methyl-L-arginine (3 mM), but not the PARS inhibitor 3-aminobenzamide (1 mM), reduced the DNA fragmentation. Stimulation with bacterial lipopolysaccharide and interferon-γ also caused a marked oxidation of proteins in the smooth muscle cells, which was inhibited by NG-methyl-L-arginine, as well as by the superoxide dismutase mimetic Mn(III)tetrakis (4-benzoic acid) porphyrin. Based on these data, we propose a role for peroxynitrite-mediated, PARS-independent pathways in the apoptotic process and in the protein oxidation in bacterial lipopolysaccharide and interferon-γ-stimulated smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)439-443
Number of pages5
JournalShock
Volume8
Issue number6
StatePublished - 1997
Externally publishedYes

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Peroxynitrous Acid
Vascular Smooth Muscle
Interferons
Smooth Muscle Myocytes
Lipopolysaccharides
DNA Fragmentation
Poly Adenosine Diphosphate Ribose
Ligases
Proteins
Arginine
Enzyme Inhibitors
Nitric Oxide Synthase
Superoxide Dismutase
Nitric Oxide

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Role of peroxynitrite in the protein oxidation and apoptotic dna fragmentation in vascular smooth muscle cells stimulated with bacterial lipopolysaccharide and interferon-γ. / O'Connor, Michael; Salzman, Andrew L.; Szabo, Csaba.

In: Shock, Vol. 8, No. 6, 1997, p. 439-443.

Research output: Contribution to journalArticle

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