Apoptosis is associated with triacyglycerol accumulation in Jurkat T-cells

被引:102
作者
Al-Saffar, NMS
Titley, JC
Robertson, D
Clarke, PA
Jackson, LE
Leach, MO
Ronen, SM
机构
[1] Royal Marsden NHS Trust, Canc Res UK Clin Magnet Resonance Res Grp, Sutton SM2 5PT, Surrey, England
[2] Royal Marsden NHS Trust, Canc Res UK Ctr Canc Therapeut, Sutton SM2 5PT, Surrey, England
[3] Royal Marsden NHS Trust, Inst Canc Res, Electron Microscopy Unit, Sutton SM2 5PT, Surrey, England
关键词
MRS; apoptosis; Fas; triacylglycerols;
D O I
10.1038/sj/bjc/6600188
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Magnetic resonance spectroscopy is increasingly used as a non-invasive method to investigate apoptosis. Apoptosis was induced in Jurkat T-cells by Fas mAb. H-1 magnetic resonance spectra of live cells showed an increase in methylene signal as well as methylene/methyl ratio of fatty acid side chains at 5 and 24 h following induction of apoptosis. To explain this observation, H-1 magnetic resonance spectra of cell extracts were investigated. These demonstrated a 70.0+/-7.0%, 114.0+/-8.0% and 90.0+/-5.0% increase in the concentration of triacyiglycerols following 3, 5 and 7 h of Fas mAb treatment (P<0.05). Confocal microscopy images of cells stained with the lipophilic dye Nile Red demonstrated the presence of lipid droplets in the cell cytoplasm. Quantification of the stained lipids by flow cytometry showed a good correlation with the magnetic resonance results (Pgreater than or equal to0.05 at 3, 5 and 7 h). P-31 magnetic resonance spectra showed a drop in phosphatidylcholine content of apoptosing cells, indicating that alteration in phosphatidylcholine metabolism could be the source of triacylglycerol accumulation during apoptosis. In summary, apoptosis is associated with an early accumulation of mobile triacylglycerols mostly in the form of cytoplasmic lipid droplets. This is reflected in an increase in the methylene/methyl ratio which could be detected by magnetic resonance spectroscopy, (C) 2002 Cancer Research UK.
引用
收藏
页码:963 / 970
页数:8
相关论文
共 27 条
[1]  
ALSAFFAR NM, 1999, P ISMRM
[2]   Inhibition of phosphatidylcholine biosynthesis following induction of apoptosis in HL-60 cells [J].
Anthony, ML ;
Zhao, M ;
Brindle, KM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (28) :19686-19692
[3]   Fas-induced arachidonic acid release is mediated by Ca2+-independent phospholipase A2 but not cytosolic phospholipase A2 which undergoes proteolytic inactivation [J].
Atsumi, G ;
Tajima, M ;
Hadano, A ;
Nakatani, Y ;
Murakami, M ;
Kudo, I .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (22) :13870-13877
[4]  
Barba I, 1999, CANCER RES, V59, P1861
[5]   Mobile lipid production after confluence and pH stress in perfused C6 cells [J].
Barba, I ;
Mann, P ;
Cabañas, ME ;
Arús, C ;
Gasparovic, C .
NMR IN BIOMEDICINE, 2001, 14 (01) :33-40
[6]  
Bhakoo KK, 1997, CELL MOL BIOL, V43, P621
[7]  
Blankenberg FG, 1996, BLOOD, V87, P1951
[8]   Quantitative analysis of apoptotic cell death using proton nuclear magnetic resonance spectroscopy [J].
Blankenberg, FG ;
Katsikis, PD ;
Storrs, RW ;
Beaulieu, C ;
Spielman, D ;
Chen, JY ;
Naumovski, L ;
Tait, JF .
BLOOD, 1997, 89 (10) :3778-3786
[9]   NMR LIPID PROFILES OF CELLS, TISSUES AND BODY-FLUIDS .1. 1D AND 2D PROTON NMR OF LIPIDS FROM RAT-LIVER [J].
CASU, M ;
ANDERSON, GJ ;
CHOI, G ;
GIBBONS, WA .
MAGNETIC RESONANCE IN CHEMISTRY, 1991, 29 (06) :594-602
[10]   MULTIPLE PATHWAYS ORIGINATE AT THE FAS/APO-1 (CD95) RECEPTOR - SEQUENTIAL INVOLVEMENT OF PHOSPHATIDYLCHOLINE-SPECIFIC PHOSPHOLIPASE-C AND ACIDIC SPHINGOMYELINASE IN THE PROPAGATION OF THE APOPTOTIC SIGNAL [J].
CIFONE, MG ;
RONCAIOLI, P ;
DEMARIA, R ;
CAMARDA, G ;
SANTONI, A ;
RUBERTI, G ;
TESTI, R .
EMBO JOURNAL, 1995, 14 (23) :5859-5868