Resveratrol-induced activation of the mitogen-activated protein kinases, ERK1 and ERK2, in human neuroblastoma SH-SY5Y cells

Phosphorylation of the mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase 1 (ERK1) and extracellular signal-regulated kinase 2 (ERK2), induced by resveratrol, a natural antioxidant present in grapes and wine, has been studied in vitro on undifferentiated and differentiated (induction by retinoic acid) SH-SY5Y human neuroblastoma cells. In undifferentiated cells resveratrol 1 mu M induced phosphorylation of ERK1 and ERK2, which was already evident at 2 min, peaked at 10 min and persisted at 30 min. A wide range (from 1 pM to 10 mu M) Of resveratrol concentrations were able to induce phosphorylation of ERK1 and ERK2, while higher concentrations (50-100 mu M) inhibited MAP kinases phosphorylation. In retinoic acid (RA) differentiated cells resveratrol (1 mu M) induced an evident increase in ERK1 and ERK2 phosphorylation. This study demonstrates that resveratrol, even at very low concentrations, may have a biological effect on neuron-like cells. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.