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Paraquat inhibits cell viability via enhanced oxidative stress and apoptosis in human neural progenitor cells.
- Source :
-
Chemico-biological interactions [Chem Biol Interact] 2013 Nov 25; Vol. 206 (2), pp. 248-55. Date of Electronic Publication: 2013 Sep 21. - Publication Year :
- 2013
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Abstract
- Paraquat (PQ) is one of the most widely used herbicides in the world. Although available evidence indicates that people exposed to PQ have a higher risk of developing Parkinson's disease, adverse effects of PQ on neural progenitor cells have not been investigated yet. In this study, we investigated the in vitro effect of PQ on immortalized human embryonic neural progenitor cells (hNPCs) by treating them with various concentrations of PQ (0, 0.1, 1, 10 and 100 μM) for 24h. We show that PQ treatment reduces the cell viability and proliferation and induces reactive oxygen species (ROS) production in a dose-dependent manner. In addition, apoptosis induced by PQ was significantly increased at a concentration of as low as 1 μM. To illustrate the underlying molecular mechanisms, we examined the caspase-3 activity, intracellular calcium level, the NF-κB activity, as well as expression of p21, p53 and metallothionein-III mRNA. PQ significantly increased caspase-3 activity at the concentration of 100 μM. Similarly, PQ triggered intracellular Ca(2+) releases and activation of NF-κB was observed after exposure of hNPCs at low concentrations of PQ (1 μM). Meanwhile, p53 and p21 mRNA transcripts were significantly up-regulated at 10 μM and 1 μM of PQ, respectively. MT-III mRNA and protein expression was significantly up-regulated at 1 μM of PQ and reached peak at 10 μM. These results suggest that PQ could reduce viability of hNPCs by inducing oxidative stress and apoptosis.<br /> (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Apoptosis drug effects
Calcium metabolism
Caspase 3 metabolism
Cell Survival drug effects
Cyclin-Dependent Kinase Inhibitor p21 genetics
Cyclin-Dependent Kinase Inhibitor p21 metabolism
Humans
Metallothionein 3
NF-kappa B metabolism
Nerve Tissue Proteins genetics
Nerve Tissue Proteins metabolism
Neural Stem Cells cytology
Neural Stem Cells metabolism
Oxidative Stress drug effects
Reactive Oxygen Species metabolism
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
Up-Regulation
Herbicides pharmacology
Neural Stem Cells drug effects
Paraquat pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 206
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 24060684
- Full Text :
- https://doi.org/10.1016/j.cbi.2013.09.010