Tissue kallikrein protects cortical neurons against in vitro ischemia-acidosis/reperfusion-induced injury through the ERK1/2 pathway

摘要: Human tissue kallikrein (hTK) gene transfer has been shown to protect neurons against cerebral ischemia/reperfusion (I/R) injury, and exogenous (TK) administration can enhance neurogenesis angiogenesis following focal cortical infarction. Previous studies have reported that acidosis is a common feature of ischemia plays critical role in brain injury. However, little known about the TK ischemia-acidosis-induced which partially caused by activation acid-sensing ion channels (ASICs). Here we report pretreatment cultured with reduced cell death induced either or oxygen glucose deprivation-acidosis/reoxygenation (OGD-A/R). Immunocytochemical staining revealed largely prevented OGD-A/R-induced neuronal morphological changes. We also observed treatment protected from OGD-A/R insults. exerted neuroprotective effects reducing production reactive species (ROS), stabilizing mitochondrial membrane potential (MMP) inhibiting caspase-3 activation, thereby attenuating oxidative stress apoptosis. In addition, found extracellular signal-regulated kinase1/2 (ERK1/2) signaling cascade but not PI3K/Akt pathway was required for survival-promoting effect on exposed OGD-A/R. Moreover, blockade ASICs had similar administration, suggesting direct indirect involvement protection. conclusion, antioxidant characteristics capable alleviating ischemia-acidosis/reperfusion-induced apoptosis promoting survival vitro through activating ERK1/2 pathways. Therefore, represents promising therapeutic strategy ischemic stroke.