PCB118-Induced Cell Proliferation Mediated by Oxidative Stress and MAPK Signaling Pathway in HELF Cells

Abstract

The present study used human lung fibroblast (HELF) cells as a test model to evaluate the role of oxidative stress (OS) and extracellular signal-regulated kinases 1/2 (ERK1/2) protein in HELF cell proliferation exposed to PCB118. Results from 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide demonstrated that PCB118 at lower concentrations stimulated proliferation of HELF cell and abrogate proliferative effect at higher dose concentrations and in a time-dependent manner. Moreover, reactive oxygen species, malondialdehyde (MDA), and superoxide dismutase showed a significant increase at higher concentrations of PCB118 than the lower concentrations with the passage of time. Antioxidant enzymes such as glutathione peroxidase exhibited decreasing trends in dose- and time-dependent manner. Lipid peroxidation assay resulted in a significant increase in MDA level in PCB118-treated HELF cells compared with controls, suggesting that OS plays a key role in PCB118-induced toxicity. Comet assay indicated a significant increase in genotoxicity at higher concentrations of PCB118 exposure than the lower concentrations. It was found that PCB118 showed expression of ERK1/2 protein after 4 hours, while after 48 hours, the protein expression was less, indicating PCB toxicity to MAPK protein of HELF cell. Oxidative stress, ERK1/2, and HELF cell proliferation exhibited correlation. The results will elaborate toxicological evaluation of PCB118 to HELF cells and will help to develop drug for PCB-induced diseases.

PCB118 Induces Inflammation of Islet Beta Cells via Activating ROS-NLRP3 Inflammasome Signaling

“…In another study, the cardiovascular mortality dosedependent association for dietary PCB exposure had a hazard ratio (HR) of 1.31 (CI 95%: 1.08 to 1.57; p trend 0.005) [30]. Han et al [3] found significantly positive associations between PCBs (including 81,105,114,118,123,126,156,157,167,169,189,28,52,101,138,153,180,209,202,205,and 208) and the risk of type 2 diabetes, and PCBs showed a linear dose-response relationship with diabetes. These findings indicate that exposure to PCBs may be a diabetogenic factor.…”

“…A long-term inflammatory response, oxidative stress, and release of ROS, as well as activation of subsequent NLRP3 inflammasome signaling, are significantly involved in the pathogenesis of diabetes [ 19 , 24 ]. Studies have shown that PCB118 can increase the production of ROS, induce oxidative stress, and activate the NLRP3 inflammasome [ 25 , 27 , 28 ]. Our study was conducted to explore the potential role and mechanisms of PCB118 and ROS-NLRP3 inflammasome signaling in the inflammation of islet beta cells and diabetes.…”

Cross-Oxygen Gradients Transcriptomic Comparison Revealed the Central Role of MAPK and Hippo in Hypoxia-Mediated Mammary Proliferation Inhibition

“…This is consistent with our study in that the excessive generation of ROS could result in a decline in cell function and cause progressive cell damage [ 24 , 25 ]. Moreover, oxidative stress was connected with inhibiting cell proliferation, and hydrogen peroxide (H 2 O 2 ) treatment was able to suppress cell proliferation [ 26 , 27 ]. This evidence suggests the occurrence of hypoxia-induced proliferation inhibition of the mammary gland via impairing its antioxidant system.…”