ORP150 protects against hypoxia/ischemia-induced neuronal death

Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum-a ssociated chaperone induced by hypoxia/ischemia. Although ORP150 was sparin gly upregulated in neurons from human brain undergoing ischemic stress, the re was robust induction in astrocytes. Cultured neurons overexpressing ORP1 50 were resistant to hypoxemic stress, whereas astrocytes with inhibited OR P150 expression were more vulnerable. Mice with targeted neuronal overexpre ssion of ORP150 had smaller strokes compared with controls. Neurons with in creased ORP150 demonstrated suppressed caspase-3-like activity and enhanced brain-derived neurotrophic factor (BDNF) under hypoxia signaling. These da ta indicate that ORP150 is an integral participant in ischemic cytoprotecti ve pathways.