title: Triacsin C inhibits the formation of 1H NMR-visible mobile lipids and lipid bodies in HuT 78 apoptotic cells.
abstract: Nuclear magnetic resonance-visible mobile lipids (ML) have been reported to accumulate during cell apoptosis in vitro and in vivo. The biogenesis, biochemical nature and structure of these lipids are still under debate. In this study, a human lymphoblastoid cell line, HuT 78, was induced to apoptosis by exposure to anti-Fas monoclonal antibodies (alpha-Fas mAb) followed by incubation for different time intervals (1-24 h, hypodiploid cell fraction, H, varying from 1% to over 60%) either in the presence or in the absence of 5.0 microM Triacsin C (TRC), specific inhibitor of long-chain acyl-CoA synthetase (ACS). The increase of ML in apoptotic cells correlated linearly with H and was associated with: (a) accumulation of intracellular lipid bodies, detected by confocal laser scanning microscopy in lipophilic dye-stained cells; (b) increases, detected by thin-layer chromatography in total lipid extracts, in the relative abundance of triacylglycerides (TAG) and cholesteryl esters (CE), with corresponding decreases of phospholipids (PL). TRC completely abolished both ML and lipid body formation in anti-Fas-treated apoptotic cells, with concomitant reversion of TAG, CE and PL to control levels, but did not alter cell viability nor did it inhibit apoptosis. ML signals detected during anti-Fas-induced apoptosis therefore appear to originate from neutral lipids assembled in intracellular lipid bodies, synthesised from cellular acyl-CoA pools.
authors.affiliation: Laboratory of Cell Biology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Egidio
authors.initials: E
authors.lastname: Iorio
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Vito
authors.forename: Francesca
authors.initials: F
authors.lastname: Spadaro
authors.forename: Carlo
authors.initials: C
authors.lastname: Ramoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Lococo
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.forename: Luisa
authors.initials: L
authors.lastname: Lenti
authors.forename: Roberto
authors.initials: R
authors.lastname: Strom
authors.forename: Franca
authors.initials: F
authors.lastname: Podo
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D014226:Triazenes / Q000494:pharmacology*; D019014:fas Receptor / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D014226:Triazenes; D019014:fas Receptor; C034613:triacsin C