Overexpression of sphingosine-1-phosphate lyase protects insulin-secreting cells against cytokine toxicity.

The Journal of Biological Chemistry
Claudine HahnE Gurgul-Convey

Abstract

Increasing evidence suggests a crucial role of inflammation in cytokine-mediated β-cell dysfunction and death in type 1 diabetes mellitus, although the mechanisms are incompletely understood. Sphingosine 1-phosphate (S1P) is a multifunctional bioactive sphingolipid involved in the development of many autoimmune and inflammatory diseases. Here, we investigated the role of intracellular S1P in insulin-secreting INS1E cells by genetically manipulating the S1P-metabolizing enzyme S1P lyase (SPL). The expression of spl was down-regulated by cytokines in INS1E cells and rat islets. Overexpression of SPL protected against cytokine toxicity. Interestingly, the SPL overexpression did not suppress the cytokine-induced NFκB-iNOS-NO pathway but attenuated calcium leakage from endoplasmic reticulum (ER) stores as manifested by lower cytosolic calcium levels, higher expression of the ER protein Sec61a, decreased dephosphorylation of Bcl-2-associated death promoter (Bad) protein, and weaker caspase-3 activation in cytokine-treated (IL-1β, TNFα, and IFNγ) cells. This coincided with reduced cytokine-mediated ER stress, indicated by measurements of CCAAT/enhancer-binding protein homologous protein (chop) and immunoglobulin heavy chain binding pr...Continue Reading

References

Mar 29, 2001·Diabetes·D L Eizirik, M I Darville
Dec 1, 2001·Science·T HlaM J Kluk
May 3, 2003·Nature Reviews. Molecular Cell Biology·Sarah Spiegel, Sheldon Milstien
Sep 23, 2003·Reviews in Endocrine & Metabolic Disorders·Alex Rabinovitch, Wilma L Suarez-Pinzon
Oct 14, 2003·Biochemical Pharmacology·Thomas Mandrup-Poulsen
Oct 23, 2003·The Journal of Biological Chemistry·Ulrike ReissJulie D Saba
May 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Inik ChangMyung-Shik Lee
Aug 25, 2005·The Journal of Biological Chemistry·Michael MaceykaSarah Spiegel
Apr 6, 2006·Journal of Biochemistry and Molecular Biology·Tarek Assad TahaLina Marie Obeid
Jun 24, 2006·Endocrinology·Suzanne G LaychockLucy D Mastrandrea
Sep 26, 2006·Biochimica Et Biophysica Acta·Nitai C HaitSarah Spiegel
Dec 13, 2006·Biochimica Et Biophysica Acta·Tarek A TahaLina M Obeid
Dec 15, 2006·Nature·Gökhan S Hotamisligil
Oct 2, 2007·Trends in Endocrinology and Metabolism : TEM·Sergio E AlvarezSarah Spiegel
Mar 3, 2009·The Journal of Biological Chemistry·Nadine HagenGerhild van Echten-Deckert
Jan 26, 2010·The Journal of Biological Chemistry·Meryem BektasRichard L Proia
Apr 8, 2010·Journal of Lipid Research·L D MastrandreaS G Laychock
Oct 21, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Graham M StrubSarah Spiegel
Dec 22, 2010·The Journal of Biological Chemistry·Maria L AllendeRichard L Proia
Jan 21, 2011·Physiological Reviews·Tom L van BelleMatthias G von Herrath
Apr 14, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ewa Gurgul-ConveySigurd Lenzen
May 7, 2011·Nature Reviews. Immunology·Sarah Spiegel, Sheldon Milstien
Jun 24, 2011·Endocrine, Metabolic & Immune Disorders Drug Targets·Claire F JessupP Toby H Coates
Nov 5, 2011·Current Opinion in Immunology·Bart O Roep, Mark Peakman
Apr 13, 2012·Endocrinology·Ewa Gurgul-ConveySigurd Lenzen
May 15, 2012·Cardiovascular Research·Matthew A Smith, Rick G Schnellmann
May 17, 2012·The Biochemical Journal·Katarzyna HanzelkaEwa Gurgul-Convey
Jul 4, 2012·Biochimica Et Biophysica Acta·Julie D Saba, Anabel S de la Garza-Rodea
Jul 17, 2012·The EMBO Journal·Nico SchäubleRichard Zimmermann
Nov 17, 2012·Biochimica Et Biophysica Acta·Kohjiro NagaoKazumitsu Ueda
Jul 11, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yanfei QiPu Xia
Aug 21, 2013·Nature Reviews. Drug Discovery·Gregory T KunkelSarah Spiegel

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Citations

Aug 22, 2018·The Analyst·Cuiping ZhangHongxiu Yu
May 7, 2019·Current Medicinal Chemistry·Daniele BottaiRiccardo Ghidoni
May 1, 2020·International Journal of Molecular Sciences·Michele Dei CasFrancesco Secundo
Aug 21, 2019·Frontiers in Pharmacology·Sara GrassiPaola Giussani
Jun 17, 2020·FEBS Letters·Woo-Jae Park, Joo-Won Park
Jan 12, 2019·Cell Death & Disease·Karolina TykaEwa Gurgul-Convey
Mar 4, 2020·Cells·Lais Brigliadori FugioAndréia Machado Leopoldino
Aug 8, 2020·Cells·Ewa Gurgul-Convey
Feb 26, 2021·Cellular Signalling·Dominik WiggerBurkhard Kleuser
Mar 27, 2021·Physiological Reports·Marie-Claude Brulhart-MeynetMiguel A Frias
Jan 5, 2019·Biochemistry·Daniel F SheehyArturo J Vegas
Sep 30, 2021·Biological Reviews of the Cambridge Philosophical Society·Mengqiao CuiHongjie Zhang

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