Circulatory heavy metals (cadmium, lead, mercury, and chromium) inversely correlate with plasma GST activity and GSH level in COPD patients and impair NOX4/Nrf2/GCLC/GST signaling pathway in cultured monocytes.

Autor: Gogoi K; Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India; Academy of Scientific and Innovative Research, CSIR-North East Institute of Science and Technology Campus, Jorhat 785006, Assam, India., Manna P; Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India; Academy of Scientific and Innovative Research, CSIR-North East Institute of Science and Technology Campus, Jorhat 785006, Assam, India., Dey T; Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India., Kalita J; Academy of Scientific and Innovative Research, CSIR-North East Institute of Science and Technology Campus, Jorhat 785006, Assam, India; Research Planning and Business Development Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India. Electronic address: kalitajk74@gmail.com., Unni BG; Research Cell, Assam Downtown University, Guwahati 781026, Assam, India., Ozah D; Clinical Centre, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India., Baruah PK; Clinical Centre, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2019 Feb; Vol. 54, pp. 269-279. Date of Electronic Publication: 2018 Oct 22.
DOI: 10.1016/j.tiv.2018.10.010
Abstrakt: This study aims to examine the hypothesis that circulatory heavy metals may be associated with lung function decline and lower plasma GST activity and GSH level in COPD patients via activating monocytes mediated by impairing the NOX4/Nrf2/GCLC/GST signaling pathway. Results showed that the blood levels of heavy metals (cadmium, lead, mercury, and chromium) were significantly higher in COPD patients of coal mine site compared to the healthy controls. The levels of heavy metals in COPD patients were significantly and negatively correlated with lung function, GST activity, and GSH level. Using flowcytometry, fluorescence spectroscopy, and immunoblotting studies we have further demonstrated that treatment with individual heavy metals dose-dependently increased the NOX4 protein expression, intracellular ROS production, and decreased the Nrf2, GCLC, and GST protein expression, GST activity, and GSH level in THP-1 monocytes. None of the treatment caused any change in cell viability compared to control. In conclusion, this study suggests that circulatory heavy metals in COPD patients of coal mine site weakened the lung function, decreased the plasma GST activity and GSH level via impairing the NOX4/Nrf2/GCLC/GST signaling pathway in monocytes, which may cause monocyte activation and initiate the COPD pathophysiology.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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