Sphingomyelinase and ceramide stimulate the expression of inducible nitric-oxide synthase in rat primary astrocytes.

The Journal of Biological Chemistry
Kalipada PahanInderjit Singh

Abstract

The sphingomyelin signal transduction pathway is known to play a role in mediating the action of various cytokines. Here we examined the possible role of the sphingomyelin signaling pathway on lipopolysaccharide (LPS)- and cytokine-mediated production of NO and the expression of inducible nitric-oxide synthase (iNOS). Sphingomyelinase (SMase) treatment of astrocytes increased the cellular levels of ceramide without the induction of NO production. However, incubation of LPS or cytokine-stimulated astrocytes with SMase or by increasing intracellular ceramide by cell-permeable ceramide analogs (C2- or C6-ceramide) or inhibitor of ceramidase (N-oleoyl ethanolamine) led to a time- and dose-dependent increase in the production of NO. This increase in NO production was accompanied by an increase in iNOS activity, iNOS protein, and iNOS mRNA. Similar to astrocytes, SMase or ceramide analogs also stimulated the LPS- and cytokine-mediated expression of iNOS in the C6 glial cell line. Since activation of NF-kappaB is necessary for the induction of iNOS, we examined the effect of SMase and C2-ceramide on the activation of NF-kappaB. Although SMase or C2-ceramide alone was ineffective in activating NF-kappaB, both stimulated the LPS-mediate...Continue Reading

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Citations

Mar 29, 2006·Cellular and Molecular Life Sciences : CMLS·K Pahan
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Arundhati Jana, Kalipada Pahan
Jul 8, 2010·Neuromolecular Medicine·Arundhati Jana, Kalipada Pahan
Oct 16, 2003·Trends in Pharmacological Sciences·Emilio ClementiJacopo Meldolesi
May 24, 2000·Brain Research Bulletin·M Colasanti, T Persichini
Sep 15, 2001·Free Radical Biology & Medicine·N Andrieu-AbadieT Levade
Jun 1, 2000·Biochimica Et Biophysica Acta·A HuwilerK Sandhoff
Nov 8, 2002·Trends in Molecular Medicine·Avihu Boneh
Jun 4, 2005·Cell Death and Differentiation·F DemarchiC Schneider
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·R H UngerL Orci
Sep 12, 2001·The Journal of Biological Chemistry·M JanaK Pahan
Aug 15, 2002·The Journal of Biological Chemistry·Subhajit DasguptaKalipada Pahan
Aug 9, 2002·The Journal of Biological Chemistry·Xiaojuan LiuKalipada Pahan
Mar 7, 2001·Antioxidants & Redox Signaling·Z GuJ R Perez-Polo
Jun 15, 2006·Antioxidants & Redox Signaling·Ramendra N Saha, Kalipada Pahan
Mar 27, 2007·Surgical Infections·Joseph CuschieriRonald V Maier
Mar 9, 1999·Alcoholism, Clinical and Experimental Research·A SlomianyB L Slomiany
Nov 27, 2008·The Journal of Pharmacology and Experimental Therapeutics·Michael M NdengeleDaniela Salvemini
Jan 22, 2011·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Avik Roy, Kalipada Pahan
Feb 9, 2010·Lipids in Health and Disease·Lide AranaAntonio Gómez-Muñoz
Aug 18, 2010·Journal of Neuroinflammation·Xiaofeng LuYingying Le
Sep 15, 2004·American Journal of Clinical Pathology·Leonie A BovenJon D Laman
Dec 13, 2003·Biological Chemistry·Hartmut KleinertUlrich Förstermann
Sep 24, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Arundhati Jana, Kalipada Pahan
Oct 29, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Arundhati Jana, Kalipada Pahan

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