Oxsterol Binding Protein-related Protein 8(ORP8) Mediates 25-OHC-induced ER Stress And Cell Apoptosis

25-hydroxycholesterol(25-OHC) is an oxidized form of cholesterol, performing a variety of biological functions. Oxsterol binding protein-related protein 8(ORP8), a member of oxysterol binding protein(OSBP)-related proteins(ORPs) family, implicated in cellular lipid homeostasis,migration and organization of the microtubule cytoskeleton. In this study, we confirmed the effects of oxysterols in different concentrations on cell proliferation and apoptosis, and the effects of ORP8 expression on sensitivity of hepatocellular carcinoma cells apoptosis. Through Western blot, Q-PCR assay and FCM, we proved that ORP8 overexpression dramatically enhanced the 25-OHC effect on HepG2 cell lines ER stress and apoptosis, while ORP8 knockdown abolished the 25-OHC effect on ER stress and cell apoptosis, suggesting a mediating role of ORP8 in ER stress and cell apoptosis induced by 25-OHC. In summary, our findings showed that different concentrations of oxysterols have different effects on cells, namely, low concentration promotes cell proliferation, but high concentrations induces apoptosis; ORP8 may mediate 25-OHC-induced ER stress and apoptosis.