Targeting c-Src Reverses Accelerated GPX-1 mRNA Decay in COPD Airway Epithelial Cells.

Targeting c-Src Reverses Accelerated GPX-1 mRNA Decay in COPD Airway Epithelial Cells. Am J Respir Cell Mol Biol. 2019 Dec 04;: Authors: Dabo AJ, Ezegbunam W, Wyman AE, Moon J, Railwah C, Lora A, Majka SM, Geraghty P, Foronjy RF Abstract Enhanced expression of the cellular antioxidant glutathione peroxidase-1 (GPX-1) prevents cigarette smoke-induced lung inflammation and tissue destruction. COPD subjects, however, have decreased airway GPX-1 levels rendering them more susceptible to disease onset and progression. The mechanisms that down regulate GPX-1 in the airway epithelium in COPD remain unknown. To ascertain these factors, analyses were conducted using human airway epithelial cells isolated from healthy and COPD human subjects and lung tissue from control and cigarette smoke exposed A/J mice. Tyrosine phosphorylation modifies GPX-1 expression and cigarette smoke actives the tyrosine kinase c-Src. Therefore, studies were conducted to evaluate the role of c-Src on GPX-1 levels in COPD. These studies identified accelerated GPX-1 mRNA decay in COPD airway epithelial cells. Targeting the tyrosine kinase c-Src with siRNA inhibited GPX-1 mRNA degradation and restored GPX-1 protein levels in human airway epithelial cells. In contrast, silencing the tyrosine kinase c-Abl or the transcriptional activator Nrf2 had no effect on GPX-1 mRNA stability. The chemical inhibitors for c-Src (saracatinib and dasanitib) restored GPX-1 mRNA levels and...
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research