Inhibition of staurosporine-induced apoptosis of endothelial cells by activated protein C requires protease-activated receptor-1 and endothelial cell protein C receptor

被引:192
作者
Mosnier, LO [1 ]
Griffin, JH [1 ]
机构
[1] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA
关键词
activated protein C; apoptosis; endothelial cell protein C receptor (EPCR); protease-activated receptor (PAR);
D O I
10.1042/BJ20030341
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
In a model of staurosporine-induced apoptosis using EAhy926 endothelial cells, inhibition of apoptosis by activated protein C was dose-dependent and required the enzyme's active site, implicating activated protein C-mediated proteolysis. Consistent with this implication, both protease-activated receptor-1 (PAR-1) and endothelial cell protein C receptor (EPCR) were required for the anti-apoptotic effects of activated protein C.
引用
收藏
页码:65 / 70
页数:6
相关论文
共 26 条
  • [11] MOLECULAR-CLONING AND EXPRESSION OF MURINE AND BOVINE ENDOTHELIAL-CELL PROTEIN C/ACTIVATED PROTEIN-C RECEPTOR (EPCR) - THE STRUCTURAL AND FUNCTIONAL CONSERVATION IN HUMAN, BOVINE, AND MURINE EPCR
    FUKUDOME, K
    ESMON, CT
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (10) : 5571 - 5577
  • [12] Gale AJ, 1997, PROTEIN SCI, V6, P132
  • [13] Activated protein C:: Potential therapy for severe sepsis, thrombosis, and stroke
    Griffin, JH
    Zlokovic, B
    Fernández, JA
    [J]. SEMINARS IN HEMATOLOGY, 2002, 39 (03) : 197 - 205
  • [14] IMMUNOBLOTTING STUDIES OF THE MOLECULAR-FORMS OF PROTEIN-C IN PLASMA
    HEEB, MJ
    SCHWARZ, HP
    WHITE, T
    LAMMLE, B
    BERRETTINI, M
    GRIFFIN, JH
    [J]. THROMBOSIS RESEARCH, 1988, 52 (01) : 33 - 43
  • [15] YOPRO-1 PERMITS CYTOFLUOROMETRIC ANALYSIS OF PROGRAMMED CELL-DEATH (APOPTOSIS) WITHOUT INTERFERING WITH CELL VIABILITY
    IDZIOREK, T
    ESTAQUIER, J
    DEBELS, F
    AMEISEN, JC
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 1995, 185 (02) : 249 - 258
  • [16] Activated protein C prevents endotoxin-induced hypotension in rats by inhibiting excessive production of nitric oxide
    Isobe, H
    Okajima, K
    Uchiba, M
    Mizutani, A
    Harada, N
    Nagasaki, A
    Okabe, K
    [J]. CIRCULATION, 2001, 104 (10) : 1171 - 1175
  • [17] Gene expression profile of antithrombotic protein C defines new mechanisms modulating inflammation and apoptosis
    Joyce, DE
    Gelbert, L
    Ciaccia, A
    DeHoff, B
    Grinnell, BW
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (14) : 11199 - 11203
  • [18] Plasmin desensitization of the PARI thrombin receptor: Kinetics, sites of truncation, and implications for thrombolytic therapy
    Kuliopulos, A
    Covic, L
    Seeley, SK
    Sheridan, PJ
    Helin, J
    Costello, CE
    [J]. BIOCHEMISTRY, 1999, 38 (14) : 4572 - 4585
  • [19] The crystal structure of the endothelial protein C receptor and a bound phospholipid
    Oganesyan, V
    Oganesyan, N
    Terzyan, S
    Qu, DF
    Dauter, Z
    Esmon, NL
    Esmon, CT
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (28) : 24851 - 24854
  • [20] The endothelial cell protein C receptor - Inhibition of activated protein C anticoagulant function without modulation of reaction with proteinase inhibitors
    Regan, LM
    StearnsKurosawa, DJ
    Kurosawa, S
    Mollica, J
    Fukudome, K
    Esmon, CT
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (29) : 17499 - 17503