Damage-induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers

We isolated a membrane-bound metallopeptidase, DINE (damage-induced neurona l endopeptidase), by differential display PCR using rat normal and axotomiz ed hypoglossal nuclei. The most marked properties of DINE were neuron-speci fic expression and a striking response to axonal injury in both the central nervous system and peripheral nervous system. For instance, cranial and sp inal nerve transection, ischemia, corpus callosum transection, and colchici ne treatment increased DINE mRNA expression in the injured neurons, whereas kainate-induced hyperexcitation, immobilization, and osmotic stress failed to up-regulate DINE mRNA. Expression of DINE in COS cells partially inhibi ted C2-ceramide-induced apoptosis, probably because of the activation of an tioxidant enzymes such as Cu/Zn-superoxide dismutase, Mn-superoxide dismuta se, and glutathione peroxidase through the proteolytic activity of DINE. Th ese data provide insight into the mechanism of how injured neurons protect themselves against neuronal death.