A novel role of lactosylceramide in the regulation of lipopolysaccharide/interferon-gamma-mediated inducible nitric oxide synthase gene expression: implications for neuroinflammatory diseases

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Ravinder PannuInderjit Singh

Abstract

In the present study a possible role of glycosphingolipids (GSLs) in inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production after spinal cord injury (SCI) in rats has been established. In primary rat astrocytes lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) treatment increased the intracellular levels of lactosylceramide (LacCer) and induced iNOS gene expression. d-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol.HCI (PDMP), a glucosylceramide synthase and LacCer synthase (galactosyltransferase, GalT-2) inhibitor, inhibited LPS/IFN-gamma induced iNOS expression, which was reversed by exogenously supplied LacCer, but not by other glycosphingolipids. LPS/IFN-gamma caused a rapid increase in the activity of GalT-2 and synthesis of LacCer. Silencing of GalT-2 gene with the use of antisense oligonucleotides resulted in decreased LPS/IFN-gamma-induced iNOS, TNF-alpha, and IL-1beta gene expression. The PDMP-mediated reduction in LacCer production and inhibition of iNOS expression correlated with decreased Ras and ERK1/2 activation along with decreased IkappaB phosphorylation, NF-kappaB DNA binding activity, and NF-kappaB-luciferase reporter activity. LacCer-mediated Ras activation was ...Continue Reading

Citations

Jun 15, 2006·Antioxidants & Redox Signaling·Ramendra N Saha, Kalipada Pahan
May 15, 2013·PloS One·Subroto ChatterjeeNorman J Haughey
Mar 7, 2014·Antioxidants & Redox Signaling·Ana I RojoAntonio Cuadrado
Apr 5, 2014·The International Journal of Neuroscience·Valentina TardivoDiego Garbossa
Dec 18, 2007·Journal of Neurochemistry·Je-Seong WonInderjit Singh
Sep 9, 2015·Frontiers in Neurology·Jorge Correale, Mauricio F Farez
Feb 2, 2015·Apoptosis : an International Journal on Programmed Cell Death·Manish BodasNeeraj Vij
Jul 28, 2009·Neuroscience Letters·Leesa BryantDaniela Salvemini
May 24, 2006·Free Radical Biology & Medicine·Je-Seong Won, Inderjit Singh
Dec 1, 2011·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Jin-Koo LeeHong-Won Suh
Nov 6, 2007·Biological & Pharmaceutical Bulletin·Jae Youl Cho
Sep 14, 2014·Nature Medicine·Lior MayoFrancisco J Quintana
Feb 9, 2020·International Journal of Molecular Sciences·Aldo A VilcaesJose L Daniotti
Feb 23, 2019·Biomedicines·Jorge CorrealeMaría Célica Ysrraelit
May 1, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susanne SchiffmannGerd Geisslinger
Oct 19, 2020·Molecular Neurodegeneration·Karim BelarbiMarie-Christine Chartier-Harlin
Feb 29, 2020·Biochemical and Biophysical Research Communications·Subroto ChatterjeeSean A Campbell
Mar 7, 2021·International Journal of Molecular Sciences·Subroto ChatterjeeWendy Li
Nov 2, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marwa ZafarullahFlora Tassone
Dec 14, 2007·Biochimica Et Biophysica Acta·Subroto Chatterjee, Ambarish Pandey

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