Hydrogen peroxide-mediated necrosis induction in HUVECs is associated with an atypical pattern of caspase-3 cleavage

被引:20
作者
Csordas, Adam [1 ]
Wick, Georg [1 ]
Bernhard, David [1 ]
机构
[1] Innsbruck Med Univ, Vasc Biol Grp, Div Expt Pathophysiol & Immunol, Innsbruck Bioctr, A-6020 Innsbruck, Austria
关键词
apoptosis; necrosis; atypical caspase-3 fragment; endothelial cells; atherosclerosis; cigarette smoke; HUVEC; ATP; serine protease;
D O I
10.1016/j.yexcr.2006.02.005
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Oxidative stress, continuously exerted during chronic inflammation, has been implicated as a major causative agent of cellular dysfunction and cell death. In the present study, we investigated the impact of oxidative stress on the mode of cell death in HUVECs using H2O2 as a model reagent. We found that the predominant form of cell death was necrosis. Necrosis induction was accompanied by a distinct mode of caspase-3 cleavage, yielding a 29-kDa fragment. While inhibition of caspases could not prevent the generation of the 29-kDa fragment, general protease inhibitors, such as leupeptin and LLNL, proved to be effective in inhibiting the distinct processing pattern of caspase-3. These results suggest that caspases can act as substrates for non-caspase proteases in cells primed for necrosis induction. Thus, the pattern of caspase-3 cleavage might reflect the proteolytic system engaged in the cell death machinery in HUVECs. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:1753 / 1764
页数:12
相关论文
共 40 条
[1]  
Amberger A, 1997, CELL STRESS CHAPERON, V2, P94, DOI 10.1379/1466-1268(1997)002<0094:CEOIVE>2.3.CO
[2]  
2
[3]   Apoptosis induced by exposure to a low steady-state concentration of H2O2 is a consequence of lysosomal rupture [J].
Antunes, F ;
Cadenas, E ;
Brunk, UT .
BIOCHEMICAL JOURNAL, 2001, 356 :549-555
[4]   Proteolytic mechanisms in necrotic cell death and neurodegeneration [J].
Artal-Sanz, M ;
Tavernarakis, N .
FEBS LETTERS, 2005, 579 (15) :3287-3296
[5]   Apoptosis induced by the histone deacetylase inhibitor sodium butyrate in human leukemic lymphoblasts [J].
Bernhard, D ;
Ausserlechner, MJ ;
Tonko, M ;
Löffler, M ;
Hartmann, BL ;
Csordas, A ;
Kofler, R .
FASEB JOURNAL, 1999, 13 (14) :1991-2001
[6]   Cigarette smoke metal-catalyzed protein oxidation leads to vascular endothelial cell contraction by depolymerization of microtubules [J].
Bernhard, D ;
Csordas, A ;
Henderson, B ;
Rossmann, A ;
Kind, M ;
Wick, G .
FASEB JOURNAL, 2005, 19 (09) :1096-1107
[7]   Disruption of vascular endothelial homeostasis by tobacco smoke - impact on atherosclerosis [J].
Bernhard, D ;
Pfister, G ;
Huck, CW ;
Kind, M ;
Salvenmoser, W ;
Bonn, GK ;
Wick, G .
FASEB JOURNAL, 2003, 17 (13) :2302-+
[8]   Inhibition of histone deacetylase activity enhances Fas receptor-mediated apoptosis in leukemic lymphoblasts [J].
Bernhard, D ;
Skvortsov, S ;
Tinhofer, I ;
Hübl, H ;
Greil, R ;
Csordas, A ;
Kofler, R .
CELL DEATH AND DIFFERENTIATION, 2001, 8 (10) :1014-1021
[9]   In vivo calpain/caspase cross-talk during 3-nitropropionic acid-induced striatal degeneration -: Implication of a calpain-mediated cleavage of active caspase-3 [J].
Bizat, N ;
Hermel, JM ;
Humbert, S ;
Jacquard, C ;
Créminon, C ;
Escartin, C ;
Saudou, F ;
Krajewski, S ;
Hantraye, P ;
Brouillet, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (44) :43245-43253
[10]   Synergistic activation of caspase-3 by m-calpain after neonatal hypoxia-ischemia - A mechanism of "pathological apoptosis"? [J].
Blomgren, K ;
Zhu, CL ;
Wang, XY ;
Karlsson, JO ;
Leverin, AL ;
Bahr, BA ;
Mallard, C ;
Hagberg, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (13) :10191-10198