Overexpression of glucose-regulated protein 94 after spinal cord injury in rats

Abstract

Glucose-regulated protein (GRP) 94 is a member of the stress protein family, which is localized in the endoplasmic reticulum (ER). Spinal cord injury (SCI) induced ER stress that results in apoptosis. However, the role of GRP94 in injury of the central nervous system remains unknown. In this study, we performed SCI in adult rats and investigated acutely the protein expression and cellular localization of GRP94 in the spinal cord. Western blot analysis revealed that GRP94 was low in normal spinal cord. It rose at 6 h after SCI, peaked at 1 day, remained for another 3 days, then declined to basal levels at 5 days after injury. Immunohistochemistry further confirmed that GRP94 immunoactivity was expressed at low levels in gray matter and white matter in normal condition and increased after SCI. Double immunofluorescence staining showed that GRP94 was co-expressed with NeuN (neuronal marker), and GFAP (astroglial marker). In addition, caspase-12, caspase-3 and phospho-c-Jun NH2-kinase (p-JNK) levels increased at 6 h, peaked at 1 day, and then gradually reduced to normal levels for 2 weeks after SCI by western blot analysis. Co-localization of GRP94/caspase-12 and GRP94/p-JNK was detected in neurons and glial cells. Taken together, these data suggest GRP94 involvement in the injury response of the adult spinal cord of the rats.