Iorio E, Di Vito M, Spadaro F, Ramoni C, Lococo E, Carnevale R,
Lenti L, Strom R, Podo F.Triacsin C inhibits the formation
of 1H NMR-visible mobile lipids and lipid bodies in HuT 78
apoptotic cells.
Biochim Biophys Acta. 2003 Oct 20;1634(1-2):1-14
Laboratory of Cell Biology, Istituto Superiore di Sanità,
Viale Regina Elena 299, 00161 Rome, Italy.
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.
PMID: 14563408
|
