BMP7 attenuates propofol induced neuron apoptosis via modulating JNK and AKT signaling

Abstract

Background The aim of this study is to elucidate the protective role of bone morphogenetic protein 7 (BMP7) in mitigating the propofol-induced apoptosis on the HT-22 cells. Method Firstly, mouse hippocampal HT22 cells were treated with propofol at the concentrations of 0, 10, 50, 100uM for 12- and 24-hours to detect the propofol induced cell viability change and apoptotic effect. Secondly, BMP7 at the concentrations of 0, 20, 40, 60 ng/ml was co-incubated for 12-hrs to test whether BMP7 application could mitigate the propofol induced pro-apoptotic effect on the H22 cells. Finally, a specific BMP7 antagonist (TWSG-1) and an AKT inhibitor Akti-1/2 were applied to further investigate the downstream signals responsible for the BMP7’s protective property. In all sections, CCK-8 and LDH assay were employed to determine the cell viability and cytotoxicity; TUNEL staining was performed to investigate the apoptotic effect, and western blotting was conducted to examine the changes of the ratios of p-AKT/AKT and p-JNK/JNK. Results Firstly, propofol at the concentrations of 10, 50 and 100uM robustly induced cell viability decline, LDH release and morphological changes after 12- and 24-hours incubation. Secondly, BMP7 treatment at the concentration of 40 ng/ml statistically relieved propofol-induced cell cytotoxicity and apoptosis after 12-hours co-incubation. Thirdly, western blotting results showed that BMP7 initiated the upregulations of both p-AKT/AKT and p-JNK/JNK signals, which was antagonized by the treatment of TWSG-1 at 1ug/ml; In the meantime, Akti-1/2 prominently downregulated the ratio of p-AKT/AKT while upregulated the ratio of p-JNK/JNK. Finally, applications of both TWSG-1 and Akti-1/2 abolished BMP7 induced neuroprotective and anti-apoptotic effect. Conclusion BMP7 plays a protective role in reversing the propofol-induced apoptotic effect on HT22 cells possibly through the modulation of the downstream signals including JNK and AKT.