Derivatives of monoglycerides as apoptotic agents in T-cells.
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.
Philippoussis
F
F
PROCREA BioSciences Inc., Division of Research & Development, 6100 Royalmount, Montréal, Québec, Canada, H4P 2R2.
Przybytkowski
E
E
Fortin
M
M
Arguin
C
C
Pande
S V
SV
Steff
A M
AM
Hugo
P
P
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
D004075:Diglycerides; D005227:Fatty Acids; D005989:Glycerides; D005990:Glycerol; D002118:Calcium