Resveratrol relieves hydrogen peroxide-induced premature senescence associated with SIRT1 in human mesenchymal stem cells

Abstract

Cellular senescence of mesenchymal stem cells (MSCs) is often induced during in vitro expansion, by multiple experimental stimuli including oxidative stress. In this study, we investigated expression of senescence-associated proteins including SIRT1 after inducing premature senescence of MSCs with hydrogen peroxide (H2O2). We also analyzed the effect of resveratrol (RSV) on premature senescence. We found that H2O2 triggered the recruitment of RCK (p54) to P-bodies in MSCs. Premature senescence of MSCs in response to H2O2 induced a decrease in SIRT1expression and activity (indirectly identified by measuring H3-K9ac). Cellular expression of p21 and phosphorylation of ERK1/2 and p38 kinases were increased in response to H2O2, whereas phosphorylation of pRb was decreased. In contrast, RSV pretreatment resulted in a decrease in the premature senescence of MSCs. In addition, RSV pretreatment before exposing cells to H2O2 not only alleviated changes in the levels of proteins that were sensitive to the H2O2 treatment (SIRT1, p21,ERK1/2 and p38) but also inhibited the decrease of SIRT1 induced by nicotinamide (NAM). Our results suggest that MSCs may exhibit an increased tolerance for H2O2-induced oxidative stress via the senescence-associated proteins that are regulated by RSV.