Protective properties of spliced X box binding protein 1 in ozone-induced spinal cord neuronal death

摘要

Administration of ozone (O-3) is often used in the treatment of low back pain. Administration of O-3 can, however, cause neurotoxicity in spinal cord neurons via induction of endoplasmic reticulum (ER) calcium (Ca2+) release and activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKII)/mitogen-activated protein kinase (MAPK) pathway. The aim of the current study was to confirm whether administration of O-3 causes ER stress and if the consequential overexpression of adenovirus-mediated spliced X box binding protein 1 (XBP1s), which is the effector of ER stress and a crucial transcriptional factor gene in charge of cell survival, has a protective effect on spinal cord neurons after O-3 exposure. To address this aim, the expression of GRP78, an ER chaperone and signaling regulator, and the expression of XBP1s in rat primary spinal cord neurons that underwent O-3 exposure were investigated. Primary neurons exposed to O-3 exhibited increased GRP78 and XBP1s expression levels. Interestingly, the effect of decreased neuron viability was blocked when cells were pretreated with Adv-XBP1s. Moreover, overexpression of XBP1s suppressed cell death caused by O-3 exposure. These results suggest that overexpression of activated XBP1s protects against neuronal cell death following O-3 exposure and that activation of the XBP1s pathway may offer a preventative way for prophylactic treatment of spinal cord neurons exposed to O-3.