Tissue kallikrein protects SH‐SY5Y neuronal cells against oxygen and glucose deprivation‐induced injury through bradykinin B2 receptor‐dependent regulation of autophagy induction

摘要: Abstract Previous studies have demonstrated that tissue kallikrein (TK) protects against cerebral ischemia injury mainly through inhibition of apoptosis via bradykinin B2 receptor (B2R). In this study, we proposed autophagy induction contributed to the neuroprotective mechanism TK. To validate hypothesis, investigated TK-induced and its signaling mechanisms in human SH-SY5Y cells exposed oxygen glucose deprivation (OGD). We found TK treatment enhanced induction, reflected by augmented LC3 conversion Beclin1 expression, decreased p62 levels increased monomeric red fluorescent protein-LC3 puncta formation. Green protein-monomeric adenovirus assay indicated maintained autophagic flux. Moreover, bafilomycin A1 (Baf.A1) caused obvious LC3-II accumulation either presence or absence Autophagy knockdown Baf.A1 abrogated effects Mitogen-activated protein kinase 1/2 (MEK1/2)/extracellular signal-regulated (ERK)1/2 AMP-activated (AMPK)/tuberous sclerosis complex 2 (TSC2)/mammalian target rapamycin (mTOR) were induced OGD stress MEK/ERK inhibitor U0126 alone elevated conditions, but impaired autophagy. Blockade AMPK/TSC2/mTOR AMPK compound C shRNA mediated α1 TSC2 abolished treated with without B2R expression was up-regulated exposure. attenuated suppressed MEK1/2/ERK1/2 conditions sum, revealed significance B2R-mediated under stress, novel involved neuropotective function B2R-dependent regulation propose depicted model for during stress: enhances (B2R)-mediated signaling, thus inducing protective The findings reported study should provide new evidence pro-survival role ischemia.