title: Inhibition of neutral Mg2+-dependent sphingomyelinase by ubiquinol-mediated plasma membrane electron transport.
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-driven electron transport may regulate the activity of the plasma membrane neutral sphingomyelinase.
authors.affiliation: Departamento de Biología Celular, Fisiología e Inmunología, Facultad de Ciencias, Universidad de Córdoba, Córdoba, Spain.
authors.forename: S F
authors.initials: SF
authors.lastname: Martín
authors.forename: C
authors.initials: C
authors.lastname: Gómez-Díaz
authors.forename: R I
authors.initials: RI
authors.lastname: Bello
authors.forename: P
authors.initials: P
authors.lastname: Navas
authors.forename: J M
authors.initials: JM
authors.lastname: Villalba
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002462:Cell Membrane / Q000201:enzymology; D004579:Electron Transport; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008274:Magnesium / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013552:Swine; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D014451:Ubiquinone; D013108:Sphingomyelin Phosphodiesterase; D008274:Magnesium; C003741:ubiquinol