Up-regulation of the Ire1-mediated signaling molecule, Bip, in ischemic rat brain

The endoplasmic reticulum (ER) is thought to play important roles in various neurological diseases via multifactorial and complex mechanisms. The Ire1-mediated signal is part of one ER signaling pathways; the signal induces the expression of an ER-resident protein, Bip/GRP78, and is thought to be involved in cell death under ER stress. In this study, we examined time-dependent Bip expression after transient middle cerebral artery occlusion and characterized the Bip-positive cells. Ire1- mediated molecules, Bip, were rapidly up-regulated in the ischemic area after 3.5 h recirculation. Their immunoreactivity continued to increase until 24-48 h. Immunofluorescence staining revealed Bip up-regulation in ischemic neurons, which were TUNEL positive. Our studies suggest that the Ire1-mediated signal might be associated with ischemic neuronal damage.