Interactions of Coenzyme Q10 and PI3K-Akt pathway
CQ10 promoted autophagy by inhibition of PI3K/Akt
Our study was the first to investigate the effects of CoQ10 on autophagy during RANKL-induced osteoclastogenesis. In addition, we revealed that the PI3K/AKT/mTOR and MAPK pathways contributed to the underlying mechanism. However, this study has several limitations. First, the present investigation involved an in vitro experiment; an in vivo experiment should be performed to confirm the results. Second, only one concentration of CoQ10 was applied to RAW264.7 cells. Different concentrations need to be explored to reach the optimum dose with no side effects.
Taken together, our results suggested that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 (R1)
CQ10 inhibits proliferation of cancer cell by inhibition of Akt
CoQ10, alone and with trolox, reduced Y79 cell viability, induced apoptosis through excess ROS generation, and decreased MMP significantly. Both treatments caused G2/M phase cell arrest. The CAM assay showed a significant reduction in endothelial cell proliferation, evidenced by fewer number of co-cultured HUVECs when exposed to CoQ10 or CoQ10 with trolox. The combination of CoQ10 and trolox significantly reduced VEGF-A, ERK, and Akt receptor levels, while CoQ10 alone significantly inhibited ERK and Akt phosphorylation. Together, CoQ10 and trolox reduced protein expression of VEGFA. CoQ10 alone and with trolox, induces apoptosis in Y79 retinoblastoma cells by inhibiting the ERK/Akt pathway and downregulating VEGFA. (R2)
CQ10 activates PI3K pathway (contrary to the papers above)
Western blotting showed that CoQ10 treatment increased the expression levels of p85α PI3K, phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase-3β (Ser9), and heat shock transcription factor, which are proteins related to the PI3K pathway in Aβ25-35 oligomers-treated NSCs. To confirm a direct role for the PI3K pathway in CoQ10-induced restoration of proliferation of NSCs inhibited by Aβ25-35 oligomers, NSCs were pretreated with a PI3K inhibitor, LY294002; the effects of CoQ10 on the proliferation of NSCs inhibited by Aβ25-35 oligomers were almost completely blocked. Together, these results suggest that CoQ10 restores Aβ25-35 oligomer-inhibited proliferation of NSCs by activating the PI3K pathway. (R3)
CQ10 activates PI3K/Akt pathway in pancreatic stellate cells
Our finding suggests that CoQ10 inhibits the activation of PSCs by suppressing autophagy through activating the PI3K/AKT/mTOR signaling pathway. CoQ10 may act as a therapeutic agent in PSC-relating pathologies and/or anti-fibrotic approaches. (R4)