Our study first proposed that
curcumin could protect human endothelial cells from the damage caused by oxidative stress via autophagy. Furthermore, our results revealed that
curcumin causes some novel cellular mechanisms that promote autophagy as a protective effect. Pretreatment with
curcumin remarkably improves the survival of human umbilical vein endothelial cells (HUVECs) from H 2O 2-induced viability loss, which specifically evokes an autophagic response. Exposed to H 2O 2,
curcumin-treated HUVECs upregulate the level of
microtubule-associated protein 1 light chain 3-II (LC3-II), the number of autophagosomes, and the degradation of p62. We show that this compound promotes BECN1 expression and inhibits the
phosphatidylinositol 3-kinase (PtdIns3K)-AKT-mechanistic target of
rapamycin (MTOR) signaling pathway.
Curcumin can also reverse FOXO1 (a mediator of autophagy) nuclear localization along with causing an elevated level of cytoplasmic acetylation of FOXO1 and the interaction of acetylated FOXO1 and ATG7, under the circumstance of oxidative stress. Additionally, knockdown of FOXO1 by
shRNA inhibits not only the protective effects that
curcumin induced, but the autophagic process, from the quantity of LC3-II to the expression of RAB7. These results suggest that
curcumin induces autophagy, indicating that
curcumin has the potential for use as an autophagic-related
antioxidant for prevention and treatment of oxidative stress. These data uncover a brand new protective mechanism involving FOXO1 as having a critical role in regulating autophagy in HUVECs, and suggest a novel role for
curcumin in inducing a beneficial form of autophagy in HUVECs, which may be a potential multitargeted therapeutic avenue for the treatment of oxidative stress-related
cardiovascular diseases.