Induction of metabotropic glutamate receptor II in neuronal HT22 Cells as a neuroprotective effect of novel phenylenediamine derivatives

Phenylenediamine derivatives can function as a hydrogen donor and reportedly exert cytoprotective effects against oxidative stress possibly by acting as an antioxidant. However, our previous report suggested that there is no critical link between the antioxidant ability of these derivatives and prevention of death of neuronal HT22 cells and that some other mechanisms may be involved in protecting neuronal cells against oxidative stress. Here we found that these derivatives might inhibit the cell death pathway by inducing metabotropic glutamate receptor II (mGluRII). By microarray analysis, a phenylenediamine derivative was proved to induce the expression of the mRNA (Grm3) encoding one of the proteins of mGluRII in HT22 cells; and 2S--ethylglutamic acid, an antagonist of mGluRII, reduced the protective effects of the derivative. Our results suggest that these compounds protect neuronal cells against oxidative stress, at least in part, by inducing the mGluRII. These compounds may thus be useful tools as mGluRII inducers in neuronal cells.