CONDUCTED BY: Universidad de Jaén
PUBLISHED ON: Food and function
In the kidney, the tissue oxygen tension is comparatively low and renders this organ more prone to hypoxic injury. In fact, hypoxia has a central role in the development and progression of renal disease.
The recovery from this situation depends on the degree to which sublethally damaged cells restore normal function.
The master regulator of the hypoxic response is the hypoxia-inducible factor-1 (HIF-1). HIF-1 activity depends on the HIF-1α subunit level which is regulated by oxygen, nitric oxide (NO), reactive oxygen species and mTOR.
Given the antioxidant and antinitrosative properties ascribed to hydroxytyrosol (HT), this study evaluates the impact of this olive oil polyphenol on the response to hypoxia in kidney cells. To that purpose, the human embryonic kidney HEK293T cell line was treated with HT and cultured under sublethal hypoxic conditions. Our results demonstrate that HT treatment decreases both, post-hypoxic reactive oxygen species and NO levels and, consequently, HIF-1α accumulation.
However, hydroxytyrosol does not affect mTOR activation or the factor inhibiting HIF level but it promotes the expression of angiogenic proteins, suggesting that HT activates an adaptive response to hypoxia in a HIF-1α-independent pathway. In fact, this effect could be endorsed to the up-regulation of the estrogen-related receptor α.
In conclusion, our results propose that in renal hypoxia, hydroxytyrosol treatment might act as an effective preventive therapeutical approach by decreasing stress and improving the adaptive response to this pathological situation.