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

被引:96
作者
Kiryu-Seo, S
Sasaki, M
Yokohama, H
Nakagomi, S
Hirayama, T
Aoki, S
Wada, K
Kiyama, H
机构
[1] Asahikawa Med Coll, Dept Anat, Asahikawa, Hokkaido 0788510, Japan
[2] Asahikawa Med Coll, Dept Oral & Maxillofacial Surg, Asahikawa, Hokkaido 0788510, Japan
[3] Asahikawa Med Coll, Dept Anesthesiol & Crit Care Med, Asahikawa, Hokkaido 0788510, Japan
[4] Asahikawa Med Coll, Dept Orthoped Surg, Asahikawa, Hokkaido 0788510, Japan
[5] Natl Inst Neurosci, Dept egenerat Neurol Dis, Kodaira, Tokyo 1878502, Japan
关键词
D O I
10.1073/pnas.070509897
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We isolated a membrane-bound metallopeptidase, DINE (damage-induced neuronal endopeptidase), by differential display PCR using rat normal and axotomized hypoglossal nuclei. The most marked properties of DINE were neuron-specific expression and a striking response to axonal injury in both the central nervous system and peripheral nervous system. For instance, cranial and spinal nerve transection, ischemia, corpus callosum transection, and colchicine 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 inhibited C2-ceramide-induced apoptosis, probably because of the activation of antioxidant enzymes such as Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, and glutathione peroxidase through the proteolytic activity of DINE. These data provide insight into the mechanism of how injured neurons protect themselves against neuronal death.
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页码:4345 / 4350
页数:6
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