Potentiation of paclitaxel-induced apoptosis by galectin-13 overexpression via activation of Ask-1-p38-MAP kinase and JNK/SAPK pathways and suppression of Akt and ERK1/2 activation in U-937 human macrophage cells

被引:29
作者
Boronkai, Arpad [1 ,2 ,3 ]
Bellyei, Szabolcs [1 ,2 ,3 ]
Szigeti, Andras [1 ,2 ,3 ]
Pozsgai, Eva [1 ,2 ]
Bognar, Zita [1 ,2 ]
Sumegi, Balazs [1 ,2 ]
Gallyas, Ferenc, Jr. [1 ,2 ]
机构
[1] Univ Pecs, Dept Biochem, Pecs, Hungary
[2] Univ Pecs, Dept Med Chem, Pecs, Hungary
[3] Univ Pecs, Inst Oncotherapy, Pecs, Hungary
关键词
Apoptosis; Cytoprotection; Galectin-13; MAPK; Ask-1; Akt; AIF; JNK; ERK; Taxol; THYMIC EPITHELIAL-CELLS; ENDOGENOUS LECTIN; RAS ACTIVATION; PROTEIN; ADHESION; INDUCTION; MEDIATE; FAMILY; SIGNAL; BINDS;
D O I
10.1016/j.ejcb.2009.07.005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Galectin-13 transcripts have been identified in several normal and malignant tissues, but the physiological function of galectin-13 is still poorly understood. Here, we present evidence for its possible role in promoting cell death in the U-937 human macrophage cell line. Transfection of U-937 human macrophages by a galectin-13 cDNA-containing mammalian expression vector increased the galectin-13 level and sensitized the cells to stress stimuli. Galectin-13 overexpression facilitated paclitaxel-induced cell death and nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease-G without inducing mitochondrial cytochrome-c release or caspase-3 activation. Immunoblot and immunofluorescence data showed that overexpression of galectin-13 induced long-term activation of c-Jun N-terminal kinase (JNK) and p38-mitogen-activated protein kinase (MAPK) pathways, as well as activation of apoptosis signal-regulating kinase-1 (Ask-1) kinase while it suppressed paclitaxel-induced long-term activation of the phosphatidilylositol-3-kinase (PI-3K)-Akt and extracellular signal-regulated kinase (ERK1/2) cytoprotective pathways. In addition, pharmacological inhibition of JNK and p38-MAPK pathways protected the cells from paclitaxel-induced cell death. All this data indicate that galectin-13 overexpression promoted apoptosis presumably by activating the Ask-1 kinase-JNK and p38-MAPK pro-apoptotic pathways and by suppressing the PI-3K-Akt and ERK1/2 cytoprotective pathways. (C) 2009 Elsevier GmbH. All rights reserved.
引用
收藏
页码:753 / 763
页数:11
相关论文
共 46 条
[1]  
Akahani S, 1997, CANCER RES, V57, P5272
[2]   HUMAN THYMIC EPITHELIAL-CELLS EXPRESS AN ENDOGENOUS LECTIN, GALECTIN-1, WHICH BINDS TO CORE-2 O-GLYCANS ON THYMOCYTES AND T-LYMPHOBLASTOID-CELLS [J].
BAUM, LG ;
PANG, M ;
PERILLO, NL ;
WU, T ;
DELEGEANE, A ;
UITTENBOGAART, CH ;
FUKUDA, M ;
SEILHAMER, JJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (03) :877-887
[3]   Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes [J].
Bernerd, F ;
Sarasin, A ;
Magnaldo, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (20) :11329-11334
[4]  
Blagosklonny MV, 1996, CANCER RES, V56, P1851
[5]   Mitochondrial redox signaling during apoptosis [J].
Cai, JY ;
Jones, DP .
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1999, 31 (04) :327-334
[6]   God must love galectins; He made so many of them [J].
Cooper, DNW ;
Barondes, SH .
GLYCOBIOLOGY, 1999, 9 (10) :979-984
[7]   ENDOGENOUS MUSCLE LECTIN INHIBITS MYOBLAST ADHESION TO LAMININ [J].
COOPER, DNW ;
MASSA, SM ;
BARONDES, SH .
JOURNAL OF CELL BIOLOGY, 1991, 115 (05) :1437-1448
[8]   Galectin-3 augments K-Ras activation and triggers a Ras signal that attenuates ERK but not phosphoinositide 3-kinase activity [J].
Elad-Sfadia, G ;
Haklai, R ;
Balan, E ;
Kloog, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (33) :34922-34930
[9]   Galectin-1 augments Ras activation and diverts Ras signals to Raf-1 at the expense of phosphoinositide 3-kinase [J].
Elad-Sfadia, G ;
Haklai, R ;
Ballan, E ;
Gabius, HJ ;
Kloog, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (40) :37169-37175
[10]  
Ellerhorst J, 1999, INT J ONCOL, V14, P225