Manara - Qatar Research Repository
Browse
The role of NF- B and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells.pdf (2.78 MB)

The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells

Download (2.78 MB)
journal contribution
submitted on 2024-03-14, 07:19 and posted on 2024-03-14, 07:19 authored by Ibraheem M. Attafi, Saleh A. Bakheet, Hesham M. Korashy

Lead (Pb) is recognized as the first heavy metal of the top six toxic air pollutants threatening human health and the second hazardous substance. Pb exposure is associated with lung impairment and high incidences of lung cancer. Nuclear factor kappa B (NF-κB) and aryl hydrocarbon receptor (AhR) signaling pathways are known to be expressed and play an important role in the lung. However, the link between Pb lung toxicity and NF-κB and/or AhR pathways remains unclear. This study was established to explore the role of NF-κB and AhR modulation in Pb-induced lung toxicity in human lung cancer A549 cells. In the current study, treatment of A549 cells with Pb significantly induced cell apoptosis as evidenced by increasing a) the percentage of cells underwent apoptosis determined by flow cytometry and b) p53 mRNA level. Pb treatment induced oxidative stress by a) increasing the formation of reactive oxygen species and b) decreasing GSTA1 mRNA levels. The toxic effects of Pb on the lung was associated with significant increases in NF-κB and AhR levels which was accompanied with increases in downstream targets genes, iNOS and CYP1A1, respectively. Inhibition of NF-κB or AhR either chemically using resveratrol or genetically using small interfering RNA (siRNA) significantly rescued A549 cells from Pb-mediated lung toxicity. The results clearly indicate that Pb-mediated lung toxicities are NF-κB and AhR-dependent mechanism.

Other Information

Published in: Toxicology Mechanisms and Methods
License: http://creativecommons.org/licenses/by-nc-nd/4.0/
See article on publisher's website: https://dx.doi.org/10.1080/15376516.2019.1687629

Funding

Open Access funding provided by the Qatar National Library.

History

Language

  • English

Publisher

Taylor & Francis

Publication Year

  • 2019

License statement

This Item is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Institution affiliated with

  • Qatar University
  • Qatar University Health - QU
  • College of Pharmacy - QU HEALTH

Usage metrics

    Qatar University

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC