Arachidonic acid inhibits neuronal nitric oxide synthase elicited by proinflammatory stimuli and promotes astrocyte survival with both exogenous and endogenous peroxynitrite via different mechanisms

Journal of Neuroscience Research
L PalombaOrazio Cantoni

Abstract

Cytosolic phospholipase A(2)-inhibited astrocytes respond to the cocktail lipopolysaccharide/interferon-gamma with an immediate formation of peroxynitrite (ONOO(-)) and a delayed lethal response. Low concentrations of arachidonic acid (ARA; i.e., <0.1 microM) cause tyrosine kinase-dependent inhibition of neuronal nitric oxide synthase (nNOS) activity, thereby suppressing formation of ONOO(-) and the ensuing lethal response. ARA promoted its effects only when given to the cultures just prior to, or in parallel with, the proinflammatory mixture. High concentrations of ARA, i.e., >3 microM, promoted cytoprotection when applied to the cultures up to 50 min after the formation of endogenous ONOO(-) had been completed or up to 30 min after addition of exogenous ONOO(-). The mechanism(s) involved in these responses was, however, independent of tyrosine kinase activation and was in fact mediated by ARA metabolites of the lipoxygenase pathway. These results are consistent with a scenario in which astrocytes respond to low or high amounts of ARA with the triggering of different pathways involved in the inflammatory response. Early nNOS inhibition mediated by very low levels of ARA is indeed critical for nuclear factor-kappaB activation, ...Continue Reading

References

Nov 10, 1995·The Journal of Biological Chemistry·M ColasantiH Suzuki
Aug 1, 1993·Trends in Neurosciences·S MurphyJ P Schwartz
Aug 1, 1994·Journal of Biochemical Toxicology·R G SchnellmannJ B Carrick
Dec 6, 1995·Molecular and Cellular Biochemistry·A P BevanB I Posner
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·H TogashiV L Dawson
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·C J SmithP C Isakson
Feb 1, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·S S BiswalJ P Kehrer
Dec 14, 2001·Proceedings of the National Academy of Sciences of the United States of America·A AlmeidaS Moncada
Dec 18, 2001·Free Radical Biology & Medicine·R P PatelV Darley-Usmar
Mar 24, 2004·Free Radical Biology & Medicine·Letizia PalombaOrazio Cantoni
Mar 27, 2004·Biochemical and Biophysical Research Communications·Ilaria TommasiniOrazio Cantoni
Jun 30, 2004·Free Radical Biology & Medicine·Silvia Mandel, Moussa B H Youdim
Jan 24, 2007·Physiological Reviews·Pál PacherLucas Liaudet
Aug 1, 2007·Journal of Neuroscience Research·Joo-Young Im, Pyung-Lim Han
May 21, 2009·Glia·Letizia PalombaOrazio Cantoni

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Citations

Jun 19, 2013·Survey of Ophthalmology·Rupali VohraMiriam Kolko
Mar 23, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Jean-Claude HonoréSylvain Chemtob

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