Activation of the Nrf2-ARE Pathway Attenuates Hyperglycemia-Mediated Injuries in Mouse Podocytes

Background: Damage to podocytes caused by excessive reactive oxygen species (ROS) contributes to onset and progression of diabetic kidney disease (DKD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensing transcription factor that can induce the expression of antioxidant enzymes. W...

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Main Authors: Cheng Wang, CuiCui Li, Hui Peng, Zengchun Ye, Jun Zhang, Xun Liu, Tanqi Lou
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2014-08-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/366307
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spelling doaj-e55943c21fb2428fa82253a1e4978c9f2020-11-24T21:30:36ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782014-08-0134389190210.1159/000366307366307Activation of the Nrf2-ARE Pathway Attenuates Hyperglycemia-Mediated Injuries in Mouse PodocytesCheng WangCuiCui LiHui PengZengchun YeJun ZhangXun LiuTanqi LouBackground: Damage to podocytes caused by excessive reactive oxygen species (ROS) contributes to onset and progression of diabetic kidney disease (DKD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensing transcription factor that can induce the expression of antioxidant enzymes. We explored whether activation of Nrf2 pathway attenuated hyperglycemia-induced injuries in mouse podocytes. Methods: Tert-Butylhydroquinone (tBHQ) and small interfering RNAs (siRNAs) were used to regulate Nrf2 expression. Apoptosis and intracellular superoxide anion production were measured by flow cytometry. The activity of the Nrf2 antioxidant pathway was measured by an antioxidant response element (ARE)-driven luciferase reporter gene assay, and Nrf2 expression was assessed by real-time PCR and western blot analyses. Results: Podocytes incubated with high-glucose (HG) medium had higher intracellular superoxide anion and hydrogen peroxide production, higher apoptosis rate, higher bovine serum albumin (BSA) permeability and lower synaptopodin expression compared with podocytes exposed normal glucose (NG) (pppConclusions: Our findings suggest that protection against activation of the Nrf2-ARE pathway in podocytes exposed to hyperglycemia. Thus, regulation of the Nrf2-ARE pathway could be a therapeutic option to combat oxidative stress and inhibit the development of DKD.http://www.karger.com/Article/FullText/366307Tert-ButylhydroquinoneNuclear factor (erythroid-derived 2)-like 2Antioxidant response elementHigh glucosePodocyte
collection DOAJ
language English
format Article
sources DOAJ
author Cheng Wang
CuiCui Li
Hui Peng
Zengchun Ye
Jun Zhang
Xun Liu
Tanqi Lou
spellingShingle Cheng Wang
CuiCui Li
Hui Peng
Zengchun Ye
Jun Zhang
Xun Liu
Tanqi Lou
Activation of the Nrf2-ARE Pathway Attenuates Hyperglycemia-Mediated Injuries in Mouse Podocytes
Cellular Physiology and Biochemistry
Tert-Butylhydroquinone
Nuclear factor (erythroid-derived 2)-like 2
Antioxidant response element
High glucose
Podocyte
author_facet Cheng Wang
CuiCui Li
Hui Peng
Zengchun Ye
Jun Zhang
Xun Liu
Tanqi Lou
author_sort Cheng Wang
title Activation of the Nrf2-ARE Pathway Attenuates Hyperglycemia-Mediated Injuries in Mouse Podocytes
title_short Activation of the Nrf2-ARE Pathway Attenuates Hyperglycemia-Mediated Injuries in Mouse Podocytes
title_full Activation of the Nrf2-ARE Pathway Attenuates Hyperglycemia-Mediated Injuries in Mouse Podocytes
title_fullStr Activation of the Nrf2-ARE Pathway Attenuates Hyperglycemia-Mediated Injuries in Mouse Podocytes
title_full_unstemmed Activation of the Nrf2-ARE Pathway Attenuates Hyperglycemia-Mediated Injuries in Mouse Podocytes
title_sort activation of the nrf2-are pathway attenuates hyperglycemia-mediated injuries in mouse podocytes
publisher Cell Physiol Biochem Press GmbH & Co KG
series Cellular Physiology and Biochemistry
issn 1015-8987
1421-9778
publishDate 2014-08-01
description Background: Damage to podocytes caused by excessive reactive oxygen species (ROS) contributes to onset and progression of diabetic kidney disease (DKD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensing transcription factor that can induce the expression of antioxidant enzymes. We explored whether activation of Nrf2 pathway attenuated hyperglycemia-induced injuries in mouse podocytes. Methods: Tert-Butylhydroquinone (tBHQ) and small interfering RNAs (siRNAs) were used to regulate Nrf2 expression. Apoptosis and intracellular superoxide anion production were measured by flow cytometry. The activity of the Nrf2 antioxidant pathway was measured by an antioxidant response element (ARE)-driven luciferase reporter gene assay, and Nrf2 expression was assessed by real-time PCR and western blot analyses. Results: Podocytes incubated with high-glucose (HG) medium had higher intracellular superoxide anion and hydrogen peroxide production, higher apoptosis rate, higher bovine serum albumin (BSA) permeability and lower synaptopodin expression compared with podocytes exposed normal glucose (NG) (pppConclusions: Our findings suggest that protection against activation of the Nrf2-ARE pathway in podocytes exposed to hyperglycemia. Thus, regulation of the Nrf2-ARE pathway could be a therapeutic option to combat oxidative stress and inhibit the development of DKD.
topic Tert-Butylhydroquinone
Nuclear factor (erythroid-derived 2)-like 2
Antioxidant response element
High glucose
Podocyte
url http://www.karger.com/Article/FullText/366307
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