Cigarette smoke extracts and cadmium induce COX-2 expression through γ-secretase-mediated p38 MAPK activation in C6 astroglia cells

PloS One
Hyun Joung LimYoung Ho Koh

Abstract

Exposure to cigarette smoke has been implicated in the progression of cerebrovascular and neurological disorders like stroke through inflammation and blood-brain barrier disruption. In this study, we investigated the signaling cascade activated by cigarette smoke extracts (CSE) and cadmium (Cd) resulting in the COX-2 induction in C6 rat astroglia cells. CSE or Cd induced Notch1 cleavage and activated p38 MAPK and CREB signaling pathways in C6 astroglia cells. Knockdown of nicastrin using siRNA or γ-secretase inhibitors, DAPT and L-685,486, reduced Notch1 cleavage and phosphorylation of p38 MAPK and CREB, while phosphorylation of ERK and JNK remained unaffected. Additionally, the blockage of γ-secretase activity did not show any effect on the phosphorylation of AKT, another upstream activator of CREB, indicating that γ-secretase-mediated CREB activation occurs via p38 MAPK. γ-secretase inhibitor also inhibited the CSE and Cd-mediated increase in the expression of COX-2. Furthermore, recombinant overexpression of Notch1 intracellular domain resulted in an increase in the expression of COX-2. Notch signaling induced by CSE and Cd induced apoptosis in C6 cells. Our results demonstrate that CSE exposure activated the p38 MAPK and CR...Continue Reading

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Citations

Sep 3, 2020·International Journal of Environmental Research and Public Health·Jihyun JeongYoung Ho Koh
Oct 20, 2020·Journal of Immunotoxicology·Thitima KasemsukPornpun Vivithanaporn
Nov 26, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Necola GuerrinaCarolyn J Baglole
Dec 29, 2020·Ecotoxicology and Environmental Safety·Zhang YimingLi Shu
Dec 3, 2021·Therapeutic Advances in Respiratory Disease·Patrick F AsareSandra Hodge

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Methods Mentioned

BETA
protein assay
transfection

Software Mentioned

SPSS

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