Upregulation of CRM1 relates to neuronal apoptosis after traumatic brain injury in adult rats.

Traumatic brain injury (TBI) initiates a complex series of neurochemical and signaling changes that leads to neuronal dysfunction and over-reactive astrocytes. There is increasing evidence that CRM1 mediated P27(Kip1), which is a potent inhibitor of G1 cyclin-dependent kinases complexes, nuclear export-dependent or -independent Jab1/CSN5, and cytoplasmic degradation in cells. Up to now, the function of CRM1 in central nervous system (CNS) is still with limited acquaintance. In our study, to investigate whether CRM1 is involved in CNS lesion, we performed a TBI model in adult rats. Western blot and RT-PCR analysis revealed that the level of protein and mRNA of CRM1 increased in ipsilateral brain cortex in comparison to the contralateral. Immunohistochemistry and immunofluorescence double labeling indicated that CRM1 was shutting into nucleus around the wound, and increased CRM1 co-localized with P27(Kip1). Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) staining suggested that CRM1 was involved in neuronal apoptosis after brain injury. We also investigated co-localization of CRM1 and active-caspase-3 in the ipsilateral brain cortex. In addition, the expression patterns of Bax and active-caspase-3 were parallel with that of CRM1. Based on our data, we suggested that CRM1 might play an important role in neuronal apoptosis following TBI, and might provide a basis for the further study on its role in regulating the expression of P27(Kip1) and cell cycle re-entry in TBI.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}