氧化还原蛋白150可保护神经元免受缺氧/缺血诱导的死亡。

ORP150 protects against hypoxia/ischemia-induced neuronal death.

作者信息

Tamatani M, Matsuyama T, Yamaguchi A, Mitsuda N, Tsukamoto Y, Taniguchi M, Che Y H, Ozawa K, Hori O, Nishimura H, Yamashita A, Okabe M, Yanagi H, Stern D M, Ogawa S, Tohyama M

机构信息

Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan.

出版信息

Nat Med. 2001 Mar;7(3):317-23. doi: 10.1038/85463.

DOI:10.1038/85463

PMID:11231630

Abstract

Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum-associated chaperone induced by hypoxia/ischemia. Although ORP150 was sparingly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes. Cultured neurons overexpressing ORP150 were resistant to hypoxemic stress, whereas astrocytes with inhibited ORP150 expression were more vulnerable. Mice with targeted neuronal overexpression of ORP150 had smaller strokes compared with controls. Neurons with increased ORP150 demonstrated suppressed caspase-3-like activity and enhanced brain-derived neurotrophic factor (BDNF) under hypoxia signaling. These data indicate that ORP150 is an integral participant in ischemic cytoprotective pathways.

摘要

氧调节蛋白150kD（ORP150）是一种由缺氧/缺血诱导产生的新型内质网相关伴侣蛋白。尽管在经历缺血应激的人脑神经元中，ORP150仅有少量上调，但在星形胶质细胞中却有显著诱导。过表达ORP150的培养神经元对低氧应激具有抗性，而ORP150表达受抑制的星形胶质细胞则更易受损。与对照组相比，神经元靶向过表达ORP150的小鼠中风面积更小。在缺氧信号传导下，ORP150增加的神经元表现出caspase - 3样活性受到抑制，脑源性神经营养因子（BDNF）增强。这些数据表明，ORP150是缺血性细胞保护途径的重要参与者。