کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1949542 | 1537764 | 2011 | 7 صفحه PDF | دانلود رایگان |
Alveolar epithelial type II cells (AT II) in which lung surfactant synthesis and secretion take place, are subjected to low magnitude stretch during normal breathing. The aim of the study was to explore the effect of mild stretch on phospholipase A2 (PLA2) activation, an enzyme known to be involved in surfactant secretion. In A549 cells (a model of AT II cells), we showed, using a fluorometric assay, that stretch triggers an increase of total PLA2 activity. Western blot experiments revealed that the cytosolic isoform cPLA2 is rapidly phosphorylated under stretch, in addition to a modest increase in cPLA2 mRNA levels. Treatment of A549 cells with selective inhibitors of the MEK/ERK pathway significantly attenuated the stretch-induced cPLA2 phosphorylation. A strong interaction of cPLA2 and pERK enzymes was demonstrated by immunoprecipitation. We also found that inhibition of PI3K pathway attenuated cPLA2 activation after stretch, without affecting pERK levels. Our results suggest that low magnitude stretch can induce cPLA2 phosphorylation through the MEK/ERK and PI3K–Akt pathways, independently.
Research highlights
► Mechanical stretch induces rapid but transient phosphorylation of cPLA2 in A549 cells.
► ERK1/2 co-immunoprecipitate with cPLA2 in quiescent A549 cells.
► ERK1/2 and PI3 kinase independently regulate the cPLA2 phosphorylation under stretch.
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1811, Issue 6, June 2011, Pages 370–376