title: Stereospecific induction of apoptosis in tumor cells via endogenous C16-ceramide and distinct transcripts.
abstract: Concentration and distribution of individual endogenous ceramide species is crucial for apoptosis induction in response to various stimuli. Exogenous ceramide analogs induce apoptosis and can in turn modify the composition/concentrations of endogenous ceramide species and associated signaling. In this study, we show here that the elevation of endogenous C16-ceramide levels is a common feature of several known apoptosis-inducing triggers like mmLDL, TNF-alpha, H2O2 and exogenous C6-ceramide. Vice versa apoptosis requires elevation of endogenous C16-ceramide levels in cells. Enantiomers of a synthetic ceramide analog HPL-1RS36N have been developed as probes and vary in their capacity to inducing apoptosis in macrophages and HT-29 cells. Apoptosis induction by the two synthetic ceramide analogs HPL-39N and HPL-1R36N correlates with generation of cellular C16-ceramide concentration. In contrast to the S-enantiomer HPL-1S36N, the R-enantiomer HPL-1R36N shows significant effects on the expression of distinct genes known to be involved in cell cycle, cell growth and cell death (CXCL10, CCL5 and TNF-alpha), similarly on apoptosis induction. Enantioselective effects on transcription induced by metabolically stable synthetic probes provide clues on molecular mechanisms of ceramide-induced signaling, as well as leads for future anti-cancer agents.
authors.affiliation: Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany; Clinic for Anaesthesiology and Intensive Care, Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Blaess
authors.affiliation: Medical and Life Sciences Faculty, Furtwangen University , Jakob-Kienzle-Strasse 17, D-78054 Villingen-Schwenningen, Germany.
authors.forename: H P
authors.initials: HP
authors.lastname: Le
authors.affiliation: Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany; Clinic for Anaesthesiology and Intensive Care, Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany.
authors.forename: R A
authors.initials: RA
authors.lastname: Claus
authors.affiliation: Medical and Life Sciences Faculty, Furtwangen University , Jakob-Kienzle-Strasse 17, D-78054 Villingen-Schwenningen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kohl
authors.affiliation: Medical and Life Sciences Faculty, Furtwangen University, Jakob-Kienzle-Strasse 17, D-78054 Villingen-Schwenningen, Germany; Fraunhofer Institute IZI, Leipzig, EXIM Department, Schillingallee 68, D-18057 Rostock, Germany.
authors.forename: H-P
authors.initials: HP
authors.lastname: Deigner