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Sodium arsenite-induced DAPK promoter hypermethylation and autophagy via ERK1/2 phosphorylation in human uroepithelial cells.
- Source :
-
Chemico-biological interactions [Chem Biol Interact] 2009 Oct 07; Vol. 181 (2), pp. 254-62. Date of Electronic Publication: 2009 Jul 03. - Publication Year :
- 2009
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Abstract
- Arsenic compounds or arsenicals are well-known toxic and carcinogenic agents. The toxic effects of arsenic that are of most concern to humans are those that occur from chronic, low-level exposure, and are associated with various human malignancies, including skin, lung and bladder cancers. In addition, arsenic could induce cell death, including apoptosis or autophagy in malignant cells. Previously, we have demonstrated that arsenite can induce autophagy and death-associated protein kinase (DAPK) promoter hypermethylation in the SV-40 immortalized human uroepithelial cell line (SV-HUC-1). However, the underlying mechanism of arsenite-induced autophagy is still unclear. In the present study, we demonstrate that arsenite can activate the extracellular signaling-regulated protein kinase 1/2 (ERK1/2) signaling pathway after treatment in SV-HUC-1 cells by using immunocytochemistry and Western blotting. In addition, our results also show an increase of autophagosomes was produced in arsenite-treated SV-HUC-1 cells by using electron microscopy. We found that, by incrementally increasing the dosages, microtubule-associated protein light chain 3B (LC3B) and Beclin-1 are important regulators for the formation of autophagosomes, in a dose-dependent manner. When the cells were pretreated with inhibitors 5-aza-CdR or U0126 for 24h, the effect of arsenite on ERK1/2, LC3B, Beclin-1 and DAPK proteins expression is suppressed. Furthermore, our results support the notion that arsenite can induce the ERK1/2 signaling pathway to stimulate autophagy and DAPK promoter hypermethylation in human uroepithelial SV-HUC-1 cells. These findings may contribute to a better understanding of the carcinogenesis of arsenite.
- Subjects :
- Cell Line
Death-Associated Protein Kinases
Enzyme Activation
Humans
Immunohistochemistry
Microscopy, Electron, Transmission
Phosphorylation
Signal Transduction
Urothelium cytology
Urothelium enzymology
Urothelium ultrastructure
Apoptosis Regulatory Proteins genetics
Arsenites toxicity
Autophagy drug effects
Calcium-Calmodulin-Dependent Protein Kinases genetics
DNA Methylation drug effects
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Promoter Regions, Genetic
Sodium Compounds toxicity
Urothelium drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 181
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 19577553
- Full Text :
- https://doi.org/10.1016/j.cbi.2009.06.020