Inhibition of neutral Mg2+-dependent sphingomyelinase by ubiquinol-mediated plasma membrane electron transport

Protoplasma
S F MartínJosé M Villalba

Abstract

Sphingomyelin is an abundant constituent of the plasma membranes of mammalian cells. Ceramide, its primary catabolic intermediate, has emerged as an important lipid signaling molecule. Previous work carried out by our group has documented that plasma membrane Mg(2+)-dependent neutral sphingomyelinase can be effectively inhibited by exogenous ubiquinol. In this work, we have tested whether or not plasma-membrane-associated electron transport can also achieve this inhibition through endogenous ubiquinol. Our results have shown that Mg(2+)-dependent neutral sphingomyelinase in isolated plasma membranes was inhibited by NAD(P)H under conditions where ubiquinone is reduced to ubiquinol. This inhibition was potentiated in the presence of an extra amount of NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2). Depletion of plasma membranes from lipophilic antioxidants by solvent extraction abolished the inhibition by reduced pyridine nucleotides without affecting the sensitivity of the neutral sphingomyelinase to exogenous ubiquinol. Reconstitution of plasma membranes with ubiquinone restored the ability of NAD(P)H to inhibit the enzyme. Our results support that the reduction of endogenous ubiquinone to ubiquinol by NAD(P)H-drive...Continue Reading

Citations

Sep 4, 2010·Antioxidants & Redox Signaling·Domenico Del PrincipeMaria Valeria Catani
Mar 31, 2004·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Norma Marchesini, Yusuf A Hannun
Dec 28, 2011·Progress in Lipid Research·Gemma FabriasRiccardo Ghidoni
Mar 22, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alfonso Varela-LópezJosé L Quiles
May 8, 2007·Mitochondrion·Plácido NavasRafael de Cabo
May 28, 2011·British Journal of Pharmacology·Daniel CanalsYusuf A Hannun
Feb 17, 2018·Critical Reviews in Food Science and Nutrition·Francisco M Gutierrez-MariscalJose Lopez-Miranda
Aug 30, 2006·Biochimica Et Biophysica Acta·Christopher J Clarke, Yusuf A Hannun
Mar 3, 2010·Mechanisms of Ageing and Development·Guillermo López-LluchPlácido Navas

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