SIRT1 is required for the effects of rapamycin on high glucose-inducing mesangial cells senescence

The mTOR deregulation has a role in chronic kidney disease including diabetic nephropathy. SIRT1 is an important participant in renal cytoprotective responses to aging and stress. However, whether both mTOR and SIRT1 are involved in high glucose-inducing mesangial cells (MCs) senescence still remains to be explored. Hence we investigate the potential functional interrelationship between these two proteins in high glucose-inducing MCs senescence. High glucose increased mTOR expression and activity, but decreased SIRT1 expression and activity. The level of mTOR was increased significantly, while the SIRT1 expression and activity was declined significantly with serial cell culture passage. The siRNA-SIRT1 and nicotinamide promoted MCs senescence. NAD or resveratrol arrested high glucose-inducing MCs senescence. Meanwhile, the effects of NAD or resveratrol on high glucose-inducing MCs senescence were also completely blocked by SiRNA-SIRT1. Rapamycin arrested MCs senescence induced by high glucose and prevented MCs senescence with serial cell culture passage, and meanwhile increased the SIRT1 expression and activity. Moreover, the effects of rapamycin on MCs senescence induced by high glucose were also completely blocked by treating cells with niacinamide or siRNA-SIRT1. These findings provide support for the hypothesis that SIRT1 is required for the effects of rapamycin on high glucose-inducing MCs senescence. (C) 2012 Elsevier Ireland Ltd. All rights reserved.