RACK1 upregulation induces neuroprotection by activating the IRE1-XBP1 signaling pathway following traumatic brain injury in rats.

RACK1 upregulation induces neuroprotection by activating the IRE1-XBP1 signaling pathway following traumatic brain injury in rats.
Exp Neurol. 2018 Mar 05;:
Authors: Ni H, Rui Q, Xu Y, Zhu J, Gao F, Dang B, Li D, Gao R, Chen G
Abstract
Receptor for activated protein kinase C 1 (RACK1) is a multifaceted scaffolding protein known to be involved in the regulation of signaling events required for neuronal protection. In the present study, we investigated the role of RACK1 in secondary brain injury in a rat traumatic brain injury (TBI) model. A weight-drop TBI model was established in Sprague Dawley rats, and RACK1 in vivo knockdown and overexpression were performed 24 h before TBI insult. The IRE1 inhibitor 3,5-dibromosalicylaldehyde (DBSA) was administered by intracerebroventricular injection 1 h after TBI insult. Real-time PCR, Western blotting, immunofluorescence, neuronal apoptosis, brain water content, and neurological scores were evaluated. Our results revealed that TBI induced increased expression of endogenous RACK1, phosphorylated inositol-requiring enzyme 1 (p-IRE1), X-box binding protein-1 (XBP1) and glucose-regulated protein 78 (GRP78) in neurons. RACK1 overexpression significantly ameliorated neuronal apoptosis, blood-brain barrier disruption, brain edema and neurological deficits at 48 h after TBI, which was concomitant with upregulation of p-IRE1, XBP1 and GRP78 expression, while its knockdown induced the opposite ef...

Source: Experimental Neurology - March 5, 2018 Category: Neurology Authors: Ni H, Rui Q, Xu Y, Zhu J, Gao F, Dang B, Li D, Gao R, Chen G Tags: Exp Neurol Source Type: research