Excessive levels of the glycolysis metabolite methylglyoxal (MG) elicit enhanced expression of adhesion molecules which foster leukocyte-endothelial cell interactions. The signaling mechanisms involved remain elusive. To address this, we investigated the signal transduction of leukocyte- and endothelial-expressed phosphoinositide 3-kinase (PI3K) effector kinases glycogen synthase kinase 3 (GSK3) and serum- and glucocorticoid-inducible kinase 1 (SGK1) in the regulation of MG-elicited leukocyte recruitment. Using intravital microscopy of mouse cremasteric microvasculature, we demonstrate that GSK3 inhibitors lithium and SB216763 mitigate MG-elicited leukocyte recruitment and microvascular hyperpermeability. In SVEC4-10EE2 endothelial cells, but not in neutrophils, MG transiently activates GSK3 by reducing inhibitory phospho-GSK3α/β (Ser21/9) which parallels decrease of phospho-Akt at early time points (
CITATION STYLE
Su, Y., Qadri, S. M., Cayabyab, F. S., Wu, L., & Liu, L. (2014). Regulation of methylglyoxal-elicited leukocyte recruitment by endothelial SGK1/GSK3 signaling. Biochimica et Biophysica Acta - Molecular Cell Research, 1843(11), 2481–2491. https://doi.org/10.1016/j.bbamcr.2014.06.018
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