title: [Sphingolipid-mediated apoptotic signaling pathways].
abstract: Various sphingolipids are being viewed as bioactive molecules and/or second messengers. Among them, ceramide (or N-acylsphingosine) and sphingosine generally behave as pro-apoptotic mediators. Indeed, ceramide mediates the death signal initiated by numerous stress agents which either stimulate its de novo synthesis or activate sphingomyelinases that release ceramide from sphingomyelin. For instance, the early generation of ceramide promoted by TNF is mediated by a neutral sphingomyelinase the activity of which is regulated by the FAN adaptor protein, thereby controlling caspase activation and the cell death programme. In addition, the activity of this neutral sphingomyelinase is negatively modulated by caveolin, a major constituent of some membrane microdomains. The enzyme sphingosine kinase also plays a crucial role in apoptosis signalling by regulating the intracellular levels of two sphingolipids having opposite effects, namely the pro-apoptotic sphingosine and the anti-apoptotic sphingosine 1-phosphate molecule. Ceramide and sphingosine metabolism therefore appears as a pivotal regulatory pathway in the determination of cell fate.
authors.affiliation: Laboratoire de Biochimie IV Maladies Métaboliques et INSERM Unité 466, Institut Louis Bugnard, CHU Rangueil, 31059 Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cuvillier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Andrieu-Abadie
authors.forename: Bruno
authors.initials: B
authors.lastname: Ségui
authors.forename: Sophie
authors.initials: S
authors.lastname: Malagarie-Cazenave
authors.forename: Claudine
authors.initials: C
authors.lastname: Tardy
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bonhoure
authors.forename: Thierry
authors.initials: T
authors.lastname: Levade
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002518:Ceramides / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013107:Sphingolipids / Q000502:physiology*; D013110:Sphingosine / Q000378:metabolism
chemical_list: D002518:Ceramides; D013107:Sphingolipids; D013110:Sphingosine