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
| Autor: | Arpad Boronkai, Eva Pozsgai, Zita Bognar, Balazs Sumegi, Andras Szigeti, Ferenc Gallyas, Szabolcs Bellyei |
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| Rok vydání: | 2009 |
| Předmět: |
Programmed cell death
Histology Paclitaxel Cell Survival MAP Kinase Kinase 4 MAP Kinase Signaling System Galectins p38 mitogen-activated protein kinases Immunoblotting Cell Culture Techniques Apoptosis Pregnancy Proteins Mitogen-activated protein kinase kinase MAP Kinase Kinase Kinase 5 Transfection p38 Mitogen-Activated Protein Kinases Pathology and Forensic Medicine Humans Protein kinase A Protein kinase B MAP kinase kinase kinase biology Kinase Chemistry Macrophages U937 Cells Cell Biology General Medicine Cell biology Enzyme Activation Mitogen-activated protein kinase Cancer research biology.protein Mitogen-Activated Protein Kinases Proto-Oncogene Proteins c-akt |
| Zdroj: | European Journal of Cell Biology. 88:753-763 |
| ISSN: | 0171-9335 |
| DOI: | 10.1016/j.ejcb.2009.07.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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