Peroxynitrite‐Induced Cytotoxicity in PC12 Cells: Evidence for an Apoptotic Mechanism Differentially Modulated by Neurotrophic Factors

• DOI: 10.1046/j.1471-4159.1995.65041543.x
• Publication Date: 2010-07-15T23:05:05Z
• Authors: Alvaro G. Estévez; Rafael Radi; Luis Barbeito; Jordan T. Shin; John A. Thompson; Joseph S. Beckman
• Keywords: Aurintricarboxylic acid; Fragmentation

Abstract: Peroxynitrite is a powerful oxidant formed by the near‐diffusion‐limited reaction of nitric oxide with superoxide. Large doses peroxynitrite (>2 m M ) resulted in rapid cell swelling and necrosis undifferentiated PC12 cells. However, brief exposure to lower concentrations (EC 50 = 850 µ initially (3–4 h) caused minimal damage low‐density cultures. By 8 h, cytoplasmic shrinkage nuclear condensation fragmentation became increasingly evident. After 24 36% peroxynitrite‐treated cells demonstrated these features associated apoptosis. In addition, 46% DNA (by terminal‐deoxynucleotide transferase‐mediated dUTP‐digoxigenin nick end‐labeling) after 7 which was inhibited posttreatment endonuclease inhibitor aurintricarboxylic acid. Serum starvation also apoptosis control (23%), percentage not altered significantly treatment. Although known be toxic cells, present study provides first indication that induces Furthermore, pretreatment nerve growth factor or insulin, but epidermal factor, protective against peroxynitrite‐induced both acidic basic fibroblast factors greatly increased peroxynitrite‐initiated apoptosis, 63 70%, respectively. Thus, specific trophic demonstrate differential regulation vitro.