PKCδ Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66Shc
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renal tubular injury by overproduction of ROS in mitochondria plays a critical role in the pathogenesis of DKD. Evidences have shown that p66Shc was involved in renal tubular injury via mitochondrial-dependent ROS pr...
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doaj-5903d12b58f84fb4980d9f49d08d1a1e2020-11-24T23:38:46ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942014-01-01201410.1155/2014/746531746531PKCδ Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66ShcPanai Song0Shikun Yang1Li Xiao2Xiaoxuan Xu3Chengyuan Tang4Yuyan Yang5Mingming Ma6Jiefu Zhu7Fuyou Liu8Lin Sun9Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, ChinaDiabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renal tubular injury by overproduction of ROS in mitochondria plays a critical role in the pathogenesis of DKD. Evidences have shown that p66Shc was involved in renal tubular injury via mitochondrial-dependent ROS production pathway, but little is known about the upstream signaling of p66Shc that leads to tubular oxidative damage under high glucose conditions. In this study, an increased PKCδ and p66Shc activation and ROS production in renal tissues of patients with diabetic nephropathy were seen and further analysis revealed a positive correlation between the tubulointerstitial damage and p-PKCδ, p-p66Shc, and ROS production. In vitro, we investigated the phosphorylation and activation of p66Shc and PKCδ during treatment of HK-2 cells with high glucose (HG). Results showed that the activation of p66Shc and PKCδ was increased in a dose- and time-dependent manner, and this effect was suppressed by Rottlerin, a pharmacologic inhibitor of PKCδ. Moreover, PKCδ siRNA partially blocked HG-induced p66Shc phosphorylation, translocation, and ROS production in HK-2 cells. Taken together, these data suggest that activation of PKCδ promotes tubular cell injury through regulating p66Shc phosphorylation and mitochondrial translocation in HG ambient.http://dx.doi.org/10.1155/2014/746531 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Panai Song Shikun Yang Li Xiao Xiaoxuan Xu Chengyuan Tang Yuyan Yang Mingming Ma Jiefu Zhu Fuyou Liu Lin Sun |
spellingShingle |
Panai Song Shikun Yang Li Xiao Xiaoxuan Xu Chengyuan Tang Yuyan Yang Mingming Ma Jiefu Zhu Fuyou Liu Lin Sun PKCδ Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66Shc Oxidative Medicine and Cellular Longevity |
author_facet |
Panai Song Shikun Yang Li Xiao Xiaoxuan Xu Chengyuan Tang Yuyan Yang Mingming Ma Jiefu Zhu Fuyou Liu Lin Sun |
author_sort |
Panai Song |
title |
PKCδ Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66Shc |
title_short |
PKCδ Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66Shc |
title_full |
PKCδ Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66Shc |
title_fullStr |
PKCδ Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66Shc |
title_full_unstemmed |
PKCδ Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66Shc |
title_sort |
pkcδ promotes high glucose induced renal tubular oxidative damage via regulating activation and translocation of p66shc |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2014-01-01 |
description |
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renal tubular injury by overproduction of ROS in mitochondria plays a critical role in the pathogenesis of DKD. Evidences have shown that p66Shc was involved in renal tubular injury via mitochondrial-dependent ROS production pathway, but little is known about the upstream signaling of p66Shc that leads to tubular oxidative damage under high glucose conditions. In this study, an increased PKCδ and p66Shc activation and ROS production in renal tissues of patients with diabetic nephropathy were seen and further analysis revealed a positive correlation between the tubulointerstitial damage and p-PKCδ, p-p66Shc, and ROS production. In vitro, we investigated the phosphorylation and activation of p66Shc and PKCδ during treatment of HK-2 cells with high glucose (HG). Results showed that the activation of p66Shc and PKCδ was increased in a dose- and time-dependent manner, and this effect was suppressed by Rottlerin, a pharmacologic inhibitor of PKCδ. Moreover, PKCδ siRNA partially blocked HG-induced p66Shc phosphorylation, translocation, and ROS production in HK-2 cells. Taken together, these data suggest that activation of PKCδ promotes tubular cell injury through regulating p66Shc phosphorylation and mitochondrial translocation in HG ambient. |
url |
http://dx.doi.org/10.1155/2014/746531 |
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