title: Synthetic ceramides induce growth arrest or apoptosis by altering cellular redox status.
abstract: Reactive oxygen species (ROS) and ceramide are each partly responsible for the signal transduction of a variety of extracellular agents. Furthermore, the application of synthetic, short-chain ceramides mimics the cellular responses to these extracellular agents. However, the significance of ROS involvement in ceramide signaling pathways is poorly understood. Here we describe that the cellular responses to C2-/C6-ceramide of growth arrest in U937 monocytes and apoptosis in Jurkat T-cells are preceded by a rise in mitochondrial peroxide production. In Jurkat T-cells, this is associated with a large time- and dose-dependent loss of cellular glutathione. However, in U937 monocytes, glutathione loss is transient. Differences in the magnitude and kinetics of this alteration in cellular redox state associate with discrete outcomes, namely growth arrest or apoptosis.
authors.affiliation: Pharmacology Research Group, Life and Health Sciences, Aston University, Aston Triangle, Birmingham, UK.
authors.forename: Darren Charles
authors.initials: DC
authors.lastname: Phillips
authors.forename: Kirsty
authors.initials: K
authors.lastname: Allen
authors.forename: Helen R
authors.initials: HR
authors.lastname: Griffiths
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002518:Ceramides / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D002518:Ceramides; C064769:N-acetylsphingosine; D010545:Peroxides; D017382:Reactive Oxygen Species; C101954:N-caproylsphingosine; D012402:Rotenone; D019328:Buthionine Sulfoximine; D005978:Glutathione; D013110:Sphingosine