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Necrotic cell death was characterized by both an increase in lactate dehydrogenase and ATP release and changes in nuclei and cell morphology (as seen with fluorescence microscopy analysis with propidium iodide and Hoechst 33342). Apoptotic cell death was characterized by nuclear fragmentation and presence of apoptotic cell bodies, by a decrease in DNA content, and by an increase in DNA fragmentation. Treatment of chromaffin cells with lipopolysaccharide (LPS) or cytokines (interferon\u2010\u03b3, tumor necrosis factor\u2010\u03b1) resulted only in apoptotic cell death. Apoptotic effects of NO\u2010inducing compounds were specifically reversed, depending on the stimuli, by the NO scavenger carboxy\u2010PTIO (CPTio) or by the NOS inhibitors L\u2010NMA and thiocitrulline. NO\u2010induced apoptotic death in chromaffin cells was concomitant to a cell cycle arrest in G<jats:sub>0<\/jats:sub>G<jats:sub>1<\/jats:sub> phase and a decrease in the number of chromaffin cells in the G<jats:sub>2<\/jats:sub>M and S phases of cell cycle. All NO\u2010producing compounds were able to induce activation of caspase 3 and cytochrome c release, and specific inhibitors of caspase 3 and 9, such as Ac\u2010DEVD\u2010CHO (CPP32) and Ac\u2010Z\u2010LEHD\u2010FMK, respectively, prevented NO\u2010induced apoptosis in chromaffin cells. These results suggest that chromaffin cells could be good models for investigating the molecular basis of degeneration in diseases showing death of catecholaminergic neurons, phenomenon in which NO plays an important role. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.20853","type":"journal-article","created":{"date-parts":[[2006,4,20]],"date-time":"2006-04-20T02:51:21Z","timestamp":1145501481000},"page":"78-96","source":"Crossref","is-referenced-by-count":22,"title":["Nitric oxide and peroxynitrite induce cellular death in bovine chromaffin cells: Evidence for a mixed necrotic and apoptotic mechanism with caspases 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