Rapid Procoagulant Phosphatidylserine Exposure Relies on High Cytosolic Calcium Rather Than on Mitochondrial Depolarization

被引:46
作者
Arachiche, Amal [2 ,3 ,4 ]
Kerbiriou-Nabias, Daniele [3 ,4 ]
Garcin, Isabelle [5 ,6 ]
Letellier, Thierry [2 ]
Dachary-Prigent, Jeanne [1 ,2 ]
机构
[1] Univ Victor Segalen Bordeaux2, INSERM, U688, F-33076 Bordeaux, France
[2] Univ Victor Segalen, Bordeaux, France
[3] INSERM, U770, F-94275 Le Kremlin Bicetre, France
[4] Univ Paris 11, Le Kremlin Bicetre, France
[5] Univ Paris 11, INSERM, UMRS757, F-91405 Orsay, France
[6] Univ Paris 11, Orsay, France
关键词
platelets; Jurkat; apoptosis; procoagulant phosphatidylserine; thrombin plus convulxin; COATED-PLATELET FORMATION; PERMEABILITY TRANSITION PORE; AMINOPHOSPHOLIPID EXPOSURE; SURFACE EXPRESSION; CYCLOSPORINE-A; SCOTT-SYNDROME; CELL-DEATH; MEMBRANE; APOPTOSIS; ACTIVATION;
D O I
10.1161/ATVBAHA.109.190926
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Objective-Relationships between intracellular Ca2+ concentration ([Ca2+](cyt)) and apoptotic events, such as mitochondrial depolarization (Delta Psi m loss) and Bcl-2 and Bad phosphorylation, were analyzed in platelets and Jurkat cells in relation to rapid procoagulant phosphatidylserine (PS) exposure. Methods and Results-Platelets were stimulated with A23187, thapsigargin (TG) and thrombin plus convulxin (Thr/Cvx), and Jurkat cells with ionomycin, in the presence or absence of cyclosporin A (CsA), a mitochondrial permeability transition pore inhibitor. Delta Psi m loss occurred when platelets were stimulated in Ca2+ medium in conditions exposing PS, but also in EGTA medium. CsA inhibited PS exposure, [Ca2+](cyt) increase, and Delta Psi m loss in platelets stimulated with TG and Thr/Cvx, but had no inhibitory effect on A23187 stimulation. CsA reduced TG-induced Ca2+ release from the endoplasmic reticulum and, consequently, external Ca2+ influx. In ionomycin-stimulated Jurkat cells, rapid PS exposure was evidenced but not Delta Psi m loss, and CsA did not inhibit the process. The status of phosphorylated Bad and Bcl-2 in both cell types remained unchanged on stimulation. Conclusions-Whether Delta Psi m loss occurs or not, PS exposure is triggered by a high [Ca2+](cyt) increase. Data further demonstrate that CsA prevents membrane scrambling by inhibiting the high [Ca2+](cyt) increase, independently of its effect on mitochondrial permeability transition pore. (Arterioscler Thromb Vasc Biol. 2009; 29: 1883-1889.)
引用
收藏
页码:1883 / 1889
页数:7
相关论文
共 41 条
[1]
Actions of ionomycin, 4-BrA23187 and a novel electrogenic Ca2+ ionophore on mitochondria in intact cells [J].
Abramov, AY ;
Duchen, MR .
CELL CALCIUM, 2003, 33 (02) :101-112
[2]
Surface expression and functional characterization of α-granule factor V in human platelets:: effects of ionophore A23187, thrombin, collagen, and convulxin [J].
Alberio, L ;
Safa, O ;
Clemetson, KJ ;
Esmon, CT ;
Dale, GL .
BLOOD, 2000, 95 (05) :1694-1702
[3]
ERK activation by Ca2+ionophores depends on Ca2+entry in lymphocytes but not in platelets, and does not conduct membrane scrambling [J].
Arachiche, A. ;
Badirou, I. ;
Dachary-Prigent, J. ;
Garcin, I. ;
Geldwerth-Feniger, D. ;
Kerbiriou-Nabias, D. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2008, 65 (23) :3861-3871
[4]
S-CYCLOPHILIN IS RETAINED INTRACELLULARLY VIA A UNIQUE COOH-TERMINAL SEQUENCE AND COLOCALIZES WITH THE CALCIUM STORAGE PROTEIN CALRETICULIN [J].
ARBER, S ;
KRAUSE, KH ;
CARONI, P .
JOURNAL OF CELL BIOLOGY, 1992, 116 (01) :113-125
[5]
The antioxidant role of coenzyme Q [J].
Bentinger, Magnus ;
Brismar, Kerstin ;
Dallner, Gustav .
MITOCHONDRION, 2007, 7 :S41-S50
[6]
The mitochondrial permeability transition from in vitro artifact to disease target [J].
Bernardi, P ;
Krauskopf, A ;
Basso, E ;
Petronilli, V ;
Blalchy-Dyson, E ;
Di Lisa, F ;
Forte, MA .
FEBS JOURNAL, 2006, 273 (10) :2077-2099
[7]
Caspase independent/dependent regulation of K+, cell shrinkage, and mitochondrial membrane potential during lymphocyte apoptosis [J].
Bortner, CD ;
Cidlowski, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (31) :21953-21962
[8]
Scott syndrome dogs have impaired coated-platelet formation and calcein-release but normal mitochondrial depolarization [J].
Brooks, M. B. ;
Catalfamo, J. L. ;
Friese, P. ;
Dale, G. L. .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2007, 5 (09) :1972-1974
[9]
Cardoso CM, 1997, BIOCHEM J, V327, P795
[10]
Simultaneous detection of changes in cytoplasmic Ca2+, aminophospholipid exposure and microvesiculation in activated platelets [J].
Dachary-Prigent, J ;
Pasquet, JM ;
Nurden, AT .
PLATELETS, 1997, 8 (06) :405-412