The study of beneficial effect and mechanism of propofol on TNF-α-induced p-Tau increase in HT22 hippocampal neurons

Background

Tau protein is a soluble microtubule-binding protein expressed in neurons. Abnormal post-translational modifications, such as hyperphosphorylation, are closely related to central nervous system inflammation and may lead to neuronal damage. Propofol has been shown to exert neuroprotective effects. In this study, we investigated the effects of propofol on TNF-α-induced p-Tau increase in hippocampal neurons and explored the underlying mechanisms.

Methods

HT22 hippocampal neurons were pretreated with propofol, and then stimulated with TNF-α. Cell viability was measured by cell counting kit-8 (CCK-8). The expression and phosphorylation of Tau, AMPK, AKT and the expression of SIRT3 were detected by Western blot. Mitophagy was detected through the mitophagy detection kit and confocal imaging of LC3B localization.

Results

TNF-α enhanced Tau phosphorylation in a time- and dose-dependent manner, and significant effects were observed at 10 ng/mL for 2 h. Pretreatment with 25 μM propofol for 1 h effectively reduced TNF-α-induced Tau phosphorylation. TNF-α activated the phosphorylation of AMPK and AKT, which was attenuated by propofol pretreatment and by AMPK inhibitor (Compound C) or AKT inhibitor (MK2206). Meanwhile, TNF-α promoted mitophagy and upregulated the expression of SIRT3, which was inhibited by propofol and by SIRT3 inhibitor (3-TYP).

Conclusions

Propofol may attenuate TNF-α-induced p-Tau expression in HT22 cells through modulation of the AMPK/AKT signaling pathway, and may inhibit TNF-α-enhanced mitophagy by affecting the AMPK/SIRT3 signaling pathway.