Paraquat inhibits cell viability via enhanced oxidative stress and apoptosis in human neural progenitor cells.
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.
School of Public Health, Fudan University, 130 DongAn Road, Shanghai 200032, PR China; School of Public Health/MOE Key Lab for Public Safety, Fudan University, Shanghai 200032, PR China.
Xiuli
X
Chang
Wen
W
Lu
Tingting
T
Dou
Xinjin
X
Wang
Dan
D
Lou
Xia
X
Sun
Zhijun
Z
Zhou
D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D006540:Herbicides / Q000494:pharmacology*; D006801:Humans; D000090023:Metallothionein 3; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D050759:Cyclin-Dependent Kinase Inhibitor p21; D006540:Herbicides; D000090023:Metallothionein 3; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3; D010269:Paraquat; D002118:Calcium
Apoptosis; Neural progenitor cells; PQ; ROS