title: Derivatives of monoglycerides as apoptotic agents in T-cells.
abstract: Recently, lipids have received considerable attention for their potential to induce apoptosis when added exogenously to cells. In this study, we directly demonstrate that murine T-cells undergo rapid apoptosis following treatment with various forms of monoglycerides, which are a family of naturally occurring lipids consisting of a single fatty acid moiety attached to a glycerol backbone. The potency of these lipids varied depending on their chemical structure, whereas glycerol backbone or corresponding fatty acids alone were ineffective. Moreover, monoglyceride-mediated apoptosis was suppressed either by Bcl-2 overexpression, treatment with a broad inhibitor of caspases, or RNA and protein synthesis inhibitors. In addition, treatment of cells with derivatives of monoglycerides induced a calcium flux, which could be inhibited by both extracellular (EGTA) or intracellular (EGTA-AM) calcium chelators. To our knowledge, this is the first report demonstrating a role for derivatives of monoglycerides as inducers of apoptosis in mammalian cells.
authors.affiliation: PROCREA BioSciences Inc., Division of Research & Development, 6100 Royalmount, Montréal, Québec, Canada, H4P 2R2.
authors.forename: F
authors.initials: F
authors.lastname: Philippoussis
authors.forename: E
authors.initials: E
authors.lastname: Przybytkowski
authors.forename: M
authors.initials: M
authors.lastname: Fortin
authors.forename: C
authors.initials: C
authors.lastname: Arguin
authors.forename: S V
authors.initials: SV
authors.lastname: Pande
authors.forename: A M
authors.initials: AM
authors.lastname: Steff
authors.forename: P
authors.initials: P
authors.lastname: Hugo
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D005989:Glycerides / Q000737:chemistry / Q000494:pharmacology*; D005990:Glycerol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
chemical_list: D004075:Diglycerides; D005227:Fatty Acids; D005989:Glycerides; D005990:Glycerol; D002118:Calcium