Stimulation Of ERK Phosphorylation By Homocysteine In Cerebellar Guanule Neuron May Be Mediated By Transactivation

ObjectiveHomocysteine acts as a potent neurotoxin that accumulates in the brain in several neurological disorders including Alzheimer's disease(AD), While the molecular mechanisms induced by increased levels of Hcy are not well understood.MethodHere we examined the consequences of treatment of primary cultured murine cerebellar guanule neuron with Hcy through cell culturing, drug treatment,western blotting,and Analysis of apoptosis rate by flowcytometroy.ResultsWe show an activation of the extracellular signal-regulated kinases (ERK₁ and ERK₂), and the phosphorylation of ERK was reduced by tyrphostin AG1478, an inhibitor of phosphorylation of the epidermal growth factor receptor (EGFR). At the same time, apoptosis induced by Hcy is aggravated, after ERK phosphorylation is stopped by AG1478.ConclusionThe role of Hcy on ERK activation suggests the involvement of a transactivation process of EGFR. And this process is neural protective.