title: Regulation of ceramide generation during macrophage apoptosis by ASMase and de novo synthesis.
abstract: The survival of macrophages depends on the presence of specific cytokines that activate survival signaling events, as well as suppressing formation of apoptosis-inducing pathways. We have previously shown that macrophages deprived of macrophage colony stimulating factor (M-CSF) produce ceramide that contributes to apoptosis of these cells, a pathway that is suppressed by exposure to oxidized LDL. In this study we have examined macrophages derived from mice lacking acid sphingomyelinase (ASMase) to ask whether these events are altered due to the impaired ability of these cells to break down sphingomyelin and produce ceramide. We found that these cells do survive better than cells from wild type mice, but they still undergo cell death and some ceramide is formed. We show that the ceramide is being produced by a de novo synthetic pathway. Therefore, ceramide production in M-CSF-deprived macrophages arises from a combination of ASMase activity and de novo synthesis.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Shih Wei
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Payman
authors.initials: P
authors.lastname: Hojabrpour
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Kolesnick
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Urs P
authors.initials: UP
authors.lastname: Steinbrecher
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez-Muñoz
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada. Electronic address: vduronio@mail.ubc.ca.
authors.forename: Vincent
authors.initials: V
authors.lastname: Duronio
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000096:biosynthesis*; D005260:Female; D008077:Lipoproteins, LDL / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061251:Primary Cell Culture; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency / Q000235:genetics*; D013109:Sphingomyelins / Q000378:metabolism*
chemical_list: D002518:Ceramides; D008077:Lipoproteins, LDL; D013109:Sphingomyelins; C099252:oxidized low density lipoprotein; D016173:Macrophage Colony-Stimulating Factor; C577975:ASMase, mouse; D013108:Sphingomyelin Phosphodiesterase
keywords: Apoptosis; Ceramide; Enzyme; Macrophage; Sphingomyelinase