title: Role of Sirtuin3 in high glucose-induced apoptosis in renal tubular epithelial cells.
abstract: The apoptosis of renal tubular epithelial cells contributes to the pathogenesis of diabetic nephropathy. High glucose-induced mitochondrial oxidative stress is considered to be an important mediator for renal tubular cell apoptosis. Sirtuin3(Sirt3), a kind of mitochondria-localized nicotinamide adenine dinucleotide(NAD+)-dependent protein deacetylase, has been reported to regulate the generation of ROS in mitochondria through regulating acetylation level and activity of several key mitochondrial enzymes. In this study, we investigated the role of Sirt3 on high glucose-induced apoptosis in HK-2 cells. High glucose decreased the protein and mRNA expression of Sirt3 in a time-dependent manner, along with increased cell apoptosis in HK-2 cells. Furthermore, high glucose-induced oxidative stress and apoptosis were reversed by Sirt3 overexpression or antioxidant treatment. Meanwhile, we also found that overexpression of Sirt3 or antioxidant could regulate the activity of Akt/FoxO signaling pathway associated with cell apoptosis in diabetic nephropathy. In conclusion, our data suggest that Sirt3 overexpression antagonize high glucose-induced apoptosis by controlling ROS accumulation and ROS-sensitive Akt/FoxO signaling pathway in HK-2 cells.
authors: Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang, 050051, China.
authors: Xiaocui
authors: X
authors: Jiao
authors: Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang, 050051, China. Electronic address: liyinghebei@126.com.
authors: Ying
authors: Y
authors: Li
authors: Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang, 050051, China.
authors: Tao
authors: T
authors: Zhang
authors: Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang, 050051, China.
authors: Maodong
authors: M
authors: Liu
authors: Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang, 050051, China.
authors: Yanqing
authors: Y
authors: Chi
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005947:Glucose / Q000493:pharmacokinetics*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000502:physiology*; D008657:Metabolic Clearance Rate; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D056566:Sirtuin 3 / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; C466093:SIRT3 protein, human; D056566:Sirtuin 3; D005947:Glucose
keywords: Apoptosis; High glucose; Oxidative stress; Renal tubular epithelial cell; Sirtuin3