SRT1720 plays a role in oxidative stress and the senescence of human trophoblast HTR8/SVneo cells induced by D-galactose through the SIRT1/FOXO3a/ROS signalling pathway

Abstract

D-galactose (D-gal) is a reducing sugar widely distributed in food. In a pregnant animal model exposed to D-gal, D-gal was found to have toxic effects on both the mother and foetus through oxidative stress. However, little is known about the effect of D-gal exposure on the placenta and its underlying mechanism. In this study, we evaluated the effects of D-gal on HTR8/SVneo cells and the mechanisms in vitro. In the present study, the activity of HTR8/SVneo human trophoblasts decreased in a time- and concentration-dependent manner after exposure to D-gal. D-gal resulted in premature senescence of HTR8/SVneo cells, as confirmed by assessing β-galactosidase (SA-β-gal) activity and the expression of senescence-related factor p21. We also verified the damage of oxidative stress induced by D-gal by measuring the expression of reactive oxygen species (ROS), sirtuin 1 (SIRT1) and forkhead box O (FOXO) 3a. SRT1720, as a SIRT1 activator, mitigated D-gal-induced oxidative stress and senescence by upregulating SIRT1 and FOXO3a expression and reducing ROS production. Our data suggest that D-gal may induce HTR8/SVneo premature ageing through the SIRT1/FOXO3a/ROS signalling pathway mediated by oxidative stress and that SIRT1 protects cells from this damage.

Keywords: Cellular senescence; D-galactose; FOXO3a; Oxidative stress; ROS; SIRT1.