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

来源：

BIOCHEMICAL JOURNAL | 2003年 / 373卷

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

页码：65 / 70

页数：6

共 26 条

[1] Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: A multicenter, randomized, placebo-controlled, single-blind, dose escalation study
Abraham, E
Reinhart, K
Svoboda, P
Seibert, A
Olthoff, D
Dal Nogare, A
Postier, R
Hempelmann, G
Butler, T
Martin, E
Zwingelstein, C
Percell, S
Shu, V
Leighton, A
Creasey, AA
[J]. CRITICAL CARE MEDICINE, 2001, 29 (11) : 2081 - 2089
[2] Efficacy and safety of recombinant human activated protein C for severe sepsis.
Bernard, GR
Vincent, JL
Laterre, P
LaRosa, SP
Dhainaut, JF
Lopez-Rodriguez, A
Steingrub, JS
Garber, GE
Helterbrand, JD
Ely, EW
Fisher, CJ
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (10) : 699 - 709
[3] Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective
Cheng, T
Liu, D
Griffin, JH
Fernández, JA
Castellino, F
Rosen, ED
Fukudome, K
Zlokovic, BV
[J]. NATURE MEDICINE, 2003, 9 (03) : 338 - 342
[4] The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor κB and mitogen-activated protein kinase pathways
Conway, EM
Van de Wouwer, M
Pollefeyt, S
Jurk, K
Van Aken, H
De Vriese, A
Weitz, JI
Weiler, H
Hellings, PW
Schaeffer, P
Herbert, JM
Collen, D
Theilmeier, G
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (05) : 565 - 577
[5] Thrombin signalling and protease-activated receptors
Coughlin, SR
[J]. NATURE, 2000, 407 (6801) : 258 - 264
[6] PERMANENT CELL-LINE EXPRESSING HUMAN FACTOR-VIII-RELATED ANTIGEN ESTABLISHED BY HYBRIDIZATION
EDGELL, CJ
MCDONALD, CC
GRAHAM, JB
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (12): : 3734 - 3737
[7] Protein C pathway in sepsis
Esmon, CT
[J]. ANNALS OF MEDICINE, 2002, 34 (7-8) : 598 - 605
[8] Regulation of blood coagulation
Esmon, CT
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 2000, 1477 (1-2): : 349 - 360
[9] Esmon CT, 2000, THROMB HAEMOSTASIS, V83, P639
[10] Structural basis for the anticoagulant activity of the thrombin-thrombomodulin complex
Fuentes-Prior, P
Iwanaga, Y
Huber, R
Pagila, R
Rumennik, G
Seto, M
Morser, J
Light, DR
Bode, W
[J]. NATURE, 2000, 404 (6777) : 518 - 525

← 1 2 3 →