u-0126 and Cicatrix

A previous study showed that quercetin inhibits astrogliosis in a scratch-wound model, but did not identify the underlying mechanisms. Here, we show that quercetin exerts no effect on apoptosis or the viability of astrocytes, but significantly inhibits their proliferation, arresting them in the G1 phase and decreasing the percentage of cells in the S and G2 phase. In addition, we found that quercetin significantly decreased the phosphorylation of ERK1/2 and FAK, a downstream ERK signaling protein. Inhibition of this pathway with U0126, an inhibitor of MAP kinase, retarded wound closure, whereas sustained p-ERK1/2 activation, induced by vanadate, restored astrocyte migration. Our findings thus indicate that quercetin inhibits healing in the scratch-wound model of primary astrocytes in two ways: blockade of the G1 to S phase cell cycle transition and inhibition of the ERK/FAK signaling pathway, which may contribute toward decreasing astroglial scar formation in vivo.

Topics: Animals; Animals, Newborn; Antioxidants; Astrocytes; Butadienes; Cell Cycle; Cell Movement; Cell Survival; Cells, Cultured; Cerebral Cortex; Cicatrix; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Focal Adhesion Kinase 1; Nitriles; Phosphorylation; Quercetin; Rats, Sprague-Dawley; Vanadates; Wound Healing