Back to Search
Start Over
Dibromoacetic acid induced Cl.Ly1+2/-9 T-cell apoptosis and activation of MAPKs signaling cascades
- Source :
- Toxicology in vitro : an international journal published in association with BIBRA. 47
- Publication Year :
- 2017
-
Abstract
- Dibromoacetic acid (DBA), a haloacetic acid by-product of disinfection of drinking water, can cause many adverse effects in test animals, including immunotoxicity. However, the underlying molecular mechanism for the immunomodulatory effects remains unclear. The present study was undertaken to help in defining some potential mechanisms for this type of toxicity. Here, Cl.Ly1+2/-9 T-cells were exposed to varying levels of DBA and then several parameters, including cell survival, apoptosis, changes in mitochondrial potentials, and effects on select kinases (i.e., p38, ERK1/2, JNK1/2) were examined. The data showed that DBA significantly decreased Cl.Ly1+2/-9 cell viability in a dose-related manner. DBA also induced apoptosis, a decrease in mitochondrial trans-membrane potential, and up-regulated the protein expression of cleaved caspase-3. Moreover, DBA increased the phosphorylation of all three mitogen-activated protein kinases (MAPKs) evaluated. Pre-treatment with specific p38, ERK1/2, and JNK1/2 inhibitors (SB203580, U0126, SP600125, respectively) attenuated the inducible phosphorylation events. DBA also induced up-regulation of mRNA levels of the MAPKs downstream transcription factors ATF-2 and Elk-1. When taken together, the results suggest that DBA could induce murine Cl.Ly1+2/-9 T-cells apoptosis through mitochondria-dependent way, and activate the MAPKs pathways and downstream transcription factors ATF-2 and Elk-1.
- Subjects :
- 0301 basic medicine
Alkylating Agents
Cell Survival
MAP Kinase Signaling System
p38 mitogen-activated protein kinases
T-Lymphocytes
Apoptosis
Acetates
Toxicology
Cell Line
03 medical and health sciences
Mice
0302 clinical medicine
Animals
Immunologic Factors
Viability assay
Phosphorylation
Transcription factor
ets-Domain Protein Elk-1
Membrane Potential, Mitochondrial
Activating Transcription Factor 2
Kinase
Chemistry
Caspase 3
Osmolar Concentration
General Medicine
Cell biology
Enzyme Activation
030104 developmental biology
Gene Expression Regulation
030220 oncology & carcinogenesis
Toxicity
Proteolysis
Dibromoacetic acid
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 18793177
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Toxicology in vitro : an international journal published in association with BIBRA
- Accession number :
- edsair.doi.dedup.....82c8696486f700744efbd6d66cc79074