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
A. Boronkai, S. Bellyei, A. Szigeti, Eva Pozsgai, Z. Bognár, B. Sümegi, F. Gallyas
University of Pécs
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.
European Journal of Cell Biology
https://doi.org/10.1016/j.ejcb.2009.07.005
MAP Kinase Kinase Kinase 5
Galectins
JNK Mitogen-Activated Protein Kinases
MAP Kinase Signaling System
Apoptosis Inducing Factor
Mitogen-Activated Protein Kinase 1
Cytochromes c
Caspase 3
Fluorescent Antibody Technique
Ask-1
Cytoprotection
Galectin-13
Taxol
Boronkai, A., Bellyei, S., Szigeti, A., Pozsgai, E., Bognár, Z., Sümegi, B., & Gallyas, F. (2009). 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. European Journal of Cell Biology, 88(12), 753-763. https://doi.org/10.1016/j.ejcb.2009.07.005
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. / Boronkai, A.; Bellyei, S.; Szigeti, A.; Pozsgai, Eva; Bognár, Z.; Sümegi, B.; Gallyas, F.
In: European Journal of Cell Biology, Vol. 88, No. 12, 12.2009, p. 753-763.
Boronkai, A, Bellyei, S, Szigeti, A, Pozsgai, E, Bognár, Z, Sümegi, B & Gallyas, F 2009, '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', European Journal of Cell Biology, vol. 88, no. 12, pp. 753-763. https://doi.org/10.1016/j.ejcb.2009.07.005
Boronkai A, Bellyei S, Szigeti A, Pozsgai E, Bognár Z, Sümegi B et al. 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. European Journal of Cell Biology. 2009 Dec;88(12):753-763. https://doi.org/10.1016/j.ejcb.2009.07.005
Boronkai, A. ; Bellyei, S. ; Szigeti, A. ; Pozsgai, Eva ; Bognár, Z. ; Sümegi, B. ; Gallyas, F. / 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. In: European Journal of Cell Biology. 2009 ; Vol. 88, No. 12. pp. 753-763.
@article{372da59f3aee450daa43d223cc1d339f,
title = "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",
abstract = "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.",
keywords = "AIF, Akt, Apoptosis, Ask-1, Cytoprotection, ERK, Galectin-13, JNK, MAPK, Taxol",
author = "A. Boronkai and S. Bellyei and A. Szigeti and Eva Pozsgai and Z. Bogn{\'a}r and B. S{\"u}megi and F. Gallyas",
doi = "10.1016/j.ejcb.2009.07.005",
journal = "European Journal of Cell Biology (Supplement)",
T1 - 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
AU - Boronkai, A.
AU - Bellyei, S.
AU - Szigeti, A.
AU - Pozsgai, Eva
AU - Bognár, Z.
AU - Sümegi, B.
AU - Gallyas, F.
N2 - 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.
AB - 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.
KW - AIF
KW - Akt
KW - Apoptosis
KW - Ask-1
KW - Cytoprotection
KW - ERK
KW - Galectin-13
KW - JNK
KW - MAPK
KW - Taxol
U2 - 10.1016/j.ejcb.2009.07.005
DO - 10.1016/j.ejcb.2009.07.005
JO - European Journal of Cell Biology (Supplement)
JF - European Journal of Cell Biology (Supplement)
10.1016/j.ejcb.2009.07.005