Endothelial cell apoptosis induced by oxidized LDL is associated with the down-regulation of the cellular caspase inhibitor FLIP

被引:132
作者
Sata, M
Walsh, K
机构
[1] Tufts Univ, St Elizabeths Med Ctr, Sch Med, Div Cardiovasc Res, Brighton, MA 02135 USA
[2] Tufts Univ, Sackler Sch Biomed Sci, Program Cell Mol & Dev Biol, Boston, MA 02111 USA
关键词
D O I
10.1074/jbc.273.50.33103
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Fas (CD-95/APO-1) is a death receptor that initiates an apoptotic signal when activated by its ligand, Fast. Normal vascular endothelial cells are resistant to Fas-mediated apoptosis though they express both Fas and Fast. Oxidized low density lipoprotein (OxLDL) or lysophosphatidylcholine (LPC), a major component of OxLDL, induces endothelial cell suicide by sensitizing endothelial cells to Fas-mediated apoptosis. Here, we show that endothelial cell apoptosis by OxLDL and LPC-C16:0 was dose-dependent and correlated with down-regulation of FLICE-inhibitory protein (FLIP), an intracellular caspase inhibitor, FLIP down-regulation also occurred when endothelial cells were treated with toxic doses of LPC-C18:0 or minimally modified low density lipoprotein (LDL), In contrast, FLIP was not down-regulated by native LDL, acetylated LDL, LPC-C12:0, cholesterol, or 7-ketocholesterol, which are not toxic to endothelial cells. The cytotoxicity of oxidized lipids was reversed by transfecting endothelial cells with a FLIP expression plasmid. The results demonstrate, for the first time, FLIP regulation under conditions that lead to pathological tissue destruction.
引用
收藏
页码:33103 / 33106
页数:4
相关论文
共 47 条
[1]   MINIMALLY MODIFIED LOW-DENSITY-LIPOPROTEIN STIMULATES MONOCYTE ENDOTHELIAL INTERACTIONS [J].
BERLINER, JA ;
TERRITO, MC ;
SEVANIAN, A ;
RAMIN, S ;
KIM, JA ;
BAMSHAD, B ;
ESTERSON, M ;
FOGELMAN, AM .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (04) :1260-1266
[2]   ROLE OF LIPOPROTEINS IN GROWTH OF HUMAN ADULT ARTERIAL ENDOTHELIAL AND SMOOTH-MUSCLE CELLS IN LOW LIPOPROTEIN-DEFICIENT SERUM [J].
CHEN, JK ;
HOSHI, H ;
MCCLURE, DB ;
MCKEEHAN, WL .
JOURNAL OF CELLULAR PHYSIOLOGY, 1986, 129 (02) :207-214
[3]   A CONSERVED DOMAIN IN BAK, DISTINCT FROM BH1 AND BH2, MEDIATES CELL-DEATH AND PROTEIN-BINDING FUNCTIONS [J].
CHITTENDEN, T ;
FLEMINGTON, C ;
HOUGHTON, AB ;
EBB, RG ;
GALLO, GJ ;
ELANGOVAN, B ;
CHINNADURAI, G ;
LUTZ, RJ .
EMBO JOURNAL, 1995, 14 (22) :5589-5596
[4]  
Dimmeler S, 1997, CIRCULATION, V95, P1760
[5]   Oxidized LDLs induce massive apoptosis of cultured human endothelial cells through a calcium-dependent pathway - Prevention by aurintricarboxylic acid [J].
EscargueilBlanc, I ;
Meilhac, O ;
Pieraggi, MT ;
Arnal, JF ;
Salvayre, R ;
NegreSalvayre, A .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1997, 17 (02) :331-339
[6]  
FRANCIS MJ, 1991, IMMUNOLOGY, V73, P249
[7]   Involvement of the CD95 (APO-1/Fas) receptor/ligand system in drug-induced apoptosis in leukemia cells [J].
Friesen, C ;
Herr, I ;
Krammer, PH ;
Debatin, KM .
NATURE MEDICINE, 1996, 2 (05) :574-577
[8]   OXIDIZED LDL AND LIPOPROTEIN(A) STIMULATE RENIN RELEASE OF JUXTAGLOMERULAR CELLS [J].
GALLE, J ;
STUNZ, P ;
SCHOLLMEYER, P ;
WANNER, C .
KIDNEY INTERNATIONAL, 1995, 47 (01) :45-52
[9]   Melanoma cell expression of Fas(Apo-1/CD95) ligand: Implications for tumor immune escape [J].
Hahne, M ;
Rimoldi, D ;
Schroter, M ;
Romero, P ;
Schreier, M ;
French, LE ;
Schneider, P ;
Bornand, T ;
Fontana, A ;
Lienard, D ;
Cerottini, JC ;
Tschopp, J .
SCIENCE, 1996, 274 (5291) :1363-1366
[10]   MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclX(L) and initiates cell death [J].
Han, DKM ;
Chaudhary, PM ;
Wright, ME ;
Friedman, C ;
Trask, BJ ;
Riedel, RT ;
Baskin, DG ;
Schwartz, SM ;
Hood, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (21) :11333-11338