Neuregulin induces sustained reactive oxygen species generation to mediate neuronal differentiation.

摘要: Neuregulins (NRGs), which are highly expressed in the nervous system, bind and activate two receptor tyrosine kinases, ErbB-3 ErbB-4. Recently, we have shown that ErbB-4 receptors PC12 cells mediate NRG-induced differentiation through MAPK signaling pathway. Here demonstrate NRG induces an increase intracellular concentration of reactive oxygen species (ROS). N-acetylcysteine, a ROS scavenger, inhibited activation Ras Erk PC12-ErbB-4 cell differentiation. These results suggest production is involved NRG-mediated neuronal can regulate Erk. Constitutively active enhanced dominant negative production, suggesting, positive regulatory loop between ROS. The mitogen, EGF, induced short-term whereas NGF, induce differentiation, prolonged production. strongly kinetics may determine whether will differentiate or proliferate.