S100A12 promotes inflammation and apoptosis in ischemia/reperfusion injury via ERK signaling in vitro study using PC12 cells.

S100A12 is a member of S100 calcium-binding proteins with effect to promote inflammation in brain damage and stroke. However, the role of S100A12 in ischemia/reperfusion (I/R) remains to be clarified. This study aimed to explore the effect of S100A12 on I/R and discover the possible mechanism. Oxygen-glucose deprivation and reperfusion (OGD/R) was used to induce I/R injury model in vitro. Knockdown or overexpression of S100A12 was utilized to explore the role of S100A12 in I/R-induced inflammation and apoptosis. Results indicated that S100A12 expression was dramatically upregulated after OGD/R. Knockdown of S100A12 inhibited, while overexpression of S100A12 enhanced, the activation of ERK1/2 protein. OGD/R also triggered the occurrence of inflammation and oxidative stress, while these effects were blunted by S100A12 silencing and aggravated by S100A12 overexpression, and the presence of MAP kinase signaling system (ERK) inhibitor MK-8353 counteracted the effect of S100A12 overexpression. Besides, S100A12 silencing abolished, while its overexpression restored, the OGD/R-induced increased apoptosis rate and pro-apoptotic proteins expression. Similarly, ERK inhibitor MK-8353 reversed the effects of S100A12 overexpression. In conclusion, S100A12 promoted OGD/R-induced inflammation, oxidative stress and apoptosis via activation of ERK signaling in vitro.