کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1919321 1535627 2012 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
SIRT1 is required for the effects of rapamycin on high glucose-inducing mesangial cells senescence
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
SIRT1 is required for the effects of rapamycin on high glucose-inducing mesangial cells senescence
چکیده انگلیسی

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.


► High glucose regulated the mTOR and SIRT1 expression in MCs.
► The siRNA-SIRT1 or nicotinamide promoted MCs senescence.
► NAD or resveratrol arrested high glucose-inducing MCs senescence.
► Rapamycin arrested MCs replicability senescence and up-regulated SIRT1 expression and activity.
► SIRT1 is required for the effects of rapamycin on high glucose-inducing MCs senescence.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mechanisms of Ageing and Development - Volume 133, Issue 6, June 2012, Pages 387–400
نویسندگان
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