Collapse of mitochondrial membrane potential and caspases activation are early events in okadaic acid-treated Caco-2 cells

被引:52
作者
Lago, J [1 ]
Santaclara, F [1 ]
Vieites, JM [1 ]
Cabado, AG [1 ]
机构
[1] CECOPESCA, ANFACO, Microbiol & Biotoxins Area, Vigo 36310, Spain
关键词
apoptosis; anoikis; okadaic acid; mitochondrial membrane potential; caspases; Caco-2; cells; F-actin;
D O I
10.1016/j.toxicon.2005.07.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Diarrhetic Shellfish Poisoning (DSP) results from the consumption of shellfish contaminated with okadaic acid (OA) or one of the dinophysistoxins (DTX). It has been reported that this toxin induces apoptosis in several cell models, but the molecular events involved in this process have not been clarified. In this report we studied intracellular signals induced by OA in Caco-2 cells: mitochondrial membrane potential, F-actin depolymerization, caspases activation, cell proliferation and cell membrane integrity. Results indicate that caspases-8 and -9 increased their activity after 30 min of OA treatment according to their role as initiator caspases. In contrast, activation of the downstream caspase-3 is a later event in the execution phase of apoptosis. Mitochondrial membrane potential changes are detected at 30 min of OA exposure indicating that this is an early response in the apoptotic cascade. F-actin depolymerization occurs after 24 It of incubation with OA and this effect is significant at low doses of the toxin. LDH is released into the culture medium, although there is not PI uptake, indicative of a significant cell death in addition to apoptosis. Moreover, OA led to a dose- and time-dependent decrease in cellular proliferation. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:579 / 586
页数:8
相关论文
共 42 条
[1]   Actin-rich spherical extrusion induced in okadaic acid-treated K562 cells by crosslinking of membrane microdomains [J].
Baba, T ;
Udaka, K ;
Terada, N ;
Ueda, H ;
Fujii, Y ;
Ohno, S ;
Sato, SB .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2003, 51 (02) :245-252
[2]  
Baldacini Olivier, 1993, Natural Toxins, V1, P361, DOI 10.1002/nt.2620010607
[3]   INHIBITORY EFFECT OF A MARINE-SPONGE TOXIN, OKADAIC ACID, ON PROTEIN PHOSPHATASES - SPECIFICITY AND KINETICS [J].
BIALOJAN, C ;
TAKAI, A .
BIOCHEMICAL JOURNAL, 1988, 256 (01) :283-290
[4]   Apoptosis: Overview and signal transduction pathways [J].
Bredesen, DE .
JOURNAL OF NEUROTRAUMA, 2000, 17 (10) :801-810
[5]   Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid-treated neuroblastoma cells [J].
Cabado, AG ;
Leira, F ;
Vieytes, MR ;
Vieites, JM ;
Botana, LM .
ARCHIVES OF TOXICOLOGY, 2004, 78 (02) :74-85
[6]  
CABADO AG, 2003, SANTIAGO COMPOSTELA, P107
[7]   Protein phosphatase 2A regulates binding of Cdc45 to the prereplication complex [J].
Chou, DM ;
Petersen, P ;
Walter, JC ;
Walter, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (43) :40520-40527
[8]   OKADAIC ACID - A NEW PROBE FOR THE STUDY OF CELLULAR-REGULATION [J].
COHEN, P ;
HOLMES, CFB ;
TSUKITANI, Y .
TRENDS IN BIOCHEMICAL SCIENCES, 1990, 15 (03) :98-102
[9]   Recent advances in the study of epigenetic effects induced by the phycotoxin okadaic acid [J].
Creppy, EE ;
Traoré, A ;
Baudrimont, I ;
Cascante, M ;
Carratú, MR .
TOXICOLOGY, 2002, 181 :433-439
[10]   CHARACTERIZATION OF A RENAL EPITHELIAL-CELL MODEL OF APOPTOSIS USING OKADAIC ACID AND THE NRK-52E CELL-LINE [J].
DAVIS, MA ;
SMITH, MW ;
CHANG, SH ;
TRUMP, BF .
TOXICOLOGIC PATHOLOGY, 1994, 22 (06) :595-605