Agonists of metabotropic glutamate receptors group II and III (mGluRs II/III) show neuroprotective effects in in vitro and in vivo models of excitotoxicity. However, their influence on neuronal apoptosis remains unknown. In this study the effect of agonists of mGluRs II/III on staurosporine (St)-evoked LDH release was estimated in undifferentiated (UN-) and retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells. It has been found that LY354740 (0.01-100 microM) and ACTP-I (0.01-100 microM), a nonspecific agonists of mGluRs group II and III, respectively when given alone had no effect on cell proliferation and cell viability. However, both of these compounds partially decreased the St-induced cell death in UN- and RA-SHSY5Y. The selective agonist of mGluR7, AMN082 in low concentrations (0.001-1 microM) had no effect on cell proliferation/viability and tended to attenuate the Stinduced toxicity only in UN-SHSY5Y. On the other hand, AMN082 in higher concentrations (>10 microM) had the cell damaging effect in both UN- and RA- SHSY5Y cells. This study indicates that agonists of mGluRs II/III have potential to attenuate cell death evoked by staurosporine - a well recognized inducer of apoptosis. Acknowledgment: The study was supported by grant No NN405611638 from the Ministry of Science and Higher Education, Warsaw, Poland.
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