Tissue kallikrein protects neurons from hypoxia/reoxygenation-induced cell injury through Homer1b/c

摘要: Abstract Previous studies have demonstrated that human tissue kallikrein (TK) gene delivery protects against mouse cerebral ischemia/reperfusion (I/R) injury through bradykinin B2 receptor (B2R) activation. We also reported exogenous TK administration can suppress glutamate- or acidosis-induced neurotoxicity the extracellular signal-regulated kinase1/2 (ERK1/2) pathway. To further explore neuroprotection mechanisms of TK, in present study we performed immunoprecipitation analysis and identified a scaffolding protein Homer1b/c using MALDI-TOF MS analysis. Here, tested hypothesis reduces cell induced by oxygen glucose deprivation/reoxygenation (OGD/R) activating Homer1b/c. found increased expression concentration- time-dependent manner. Moreover, facilitated translocation to plasma membrane under OGD/R condition confocal microscope assays. observed overexpression showed OGD/R-induced enhancing survival, reducing LDH release, caspase-3 activity apoptosis. However, knockdown small interfering RNA opposite effects, indicating had protective effects neuronal injury. More interestingly, exerted its much more significantly neuroprotective after overexpression, whereas it reduced knockdown. In addition, pretreatment phosphorylation ERK1/2 Akt–GSK3β The beneficial were abolished PI3K antagonist. Therefore, propose novel signaling involved anti-hypoxic function activation Homer1b/c-ERK1/2 Homer1b/c-PI3K–Akt pathways.