Hydroxytyrosol Alleviated Hypoxia-Mediated PC12 Cell Damage through Activating PI3K/AKT/mTOR-HIF-1α Signaling

BACKGROUND: Hypoxia exerts pressure on cells and organisms, and this pressure can occur under both pathological and nonpathological conditions. There are many reports confirmed that hydroxytyrosol has good in vitro antioxidant activity, while the research about hydroxytyrosol on hypoxia-mediated cell damage is still unclear. PURPOSE: The aim of this study was to investigate the effect and mechanism of hydroxytyrosol on hypoxia-mediated cell damage. METHODS: We studied the effects of hydroxytyrosol on the content of reactive oxygen species, the change of antioxidant enzymes activity of SOD, CAT, and GSH-Px and the content of oxidation products MDA and GSH, and the changes of cell membrane potential and effect on PI3K/AKT/mTOR-HIF-1α signaling pathway under hypoxia-mediated PC12 cell. RESULTS: PC12 cell treated with hydroxytyrosol abated the cell apoptosis and alleviated the oxidative stress through scavenging of reactive oxygen species, improving the enzyme activity and changing the content of oxidation products and alleviating mitochondria damage. Western blotting confirmed that the mechanism maybe related to the PI3K/AKT/mTOR-HIF-1α signaling pathway. The inhibition experiment confirmed that hydroxytyrosol takes part in the expression of protein PI3K and p-mTOR. CONCLUSION: Hydroxytyrosol reduced the oxidative stress and resisted the inhibition of PI3K/AKT/mTOR-HIF-1α signaling pathway caused by hypoxia, improved cell apoptosis, and ameliorated the antihypoxia ability of PC12 cells under hypoxia.