Urban particulate matter regulates tight junction proteins by inducing oxidative stress via the Akt signal pathway in human nasal epithelial cells
Autor: | Hwa Young Lee, Hyunsu Choi, Jeong-Min Oh, Joohyung Lee, Dong Chang Lee, Junuk Lee, Ji Young Kang |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Cell Survival p38 mitogen-activated protein kinases Turbinates Toxicology Occludin medicine.disease_cause Tight Junctions Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine medicine Humans Protein phosphorylation Protein kinase B Cells Cultured Air Pollutants Tight Junction Proteins Tight junction Chemistry Urbanization Epithelial Cells General Medicine Middle Aged Acetylcysteine Cell biology Nasal Mucosa Oxidative Stress 030104 developmental biology Gene Expression Regulation Cytokines Phosphorylation Female Particulate Matter Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Oxidative stress Signal Transduction |
Zdroj: | Toxicology Letters. 333:33-41 |
ISSN: | 0378-4274 |
Popis: | Recent studies have revealed that increased reactive oxidative stress (ROS) induced by particulate matter (PM) affects tight junction (TJ) functions; however, the molecular mechanisms underlying this effect have not been evaluated fully. Cultured human epithelial cells obtained from inferior turbinate tissues were exposed to an urban PM (UPM) standard reference material (SRM 1648a). Intracellular ROS level and expression of proinflammatory cytokines and TJ proteins were examined. Expression level of phosphorylated (p)-Akt, p38, p65 were compared between exposed and unexposed cells. Cells were pretreated with the ROS scavenger N-acetylcysteine (NAC) or Akt inhibitor MK-2206 before exposure to determine whether the changes in cellular ROS and TJ protein expression could be reversed. Exposure to UPM significantly increased ROS levels and inflammatory cytokine expression levels, and decreased expression of TJ proteins zonula occludins (ZO)-1, occludin, claudin-1, and E-cadherin. UPM exposure increased p-Akt, p-p38, and p65 expression levels, and NAC pretreatment reversed these effects. Akt inhibition decreased UPM-induced ROS formation and p38 and p65 protein phosphorylation, and restored the decreased ZO-1 and E-cadherin expression. Akt inhibition and ROS scavenging may provide targets for maintaining epithelial integrity by restoring decreased TJ protein expression during exposure to UPM. |
Databáze: | OpenAIRE |
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