Neuroprotective effects of an Nrf2 agonist on high glucose-induced damage in HT22 cells

Abstract Background: Oxidative stress is the hallmark of diabetic encephalopathy, which may be caused by hyperglycaemic toxicity. We aimed to discover pharmacologic targets to restore redox homeostasis. We identified the transcription factor Nrf2 as such a target. Methods: HT22 cells were cultured...

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Autores principales: Zhao,Jiangpei, Liu,Lerong, Li,Xia, Zhang,Lingxiao, Lv,Jing, Guo,Xueli, Chen,Hui, Zhao,Tongfeng
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2019
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100249
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spelling oai:scielo:S0716-976020190001002492019-10-10Neuroprotective effects of an Nrf2 agonist on high glucose-induced damage in HT22 cellsZhao,JiangpeiLiu,LerongLi,XiaZhang,LingxiaoLv,JingGuo,XueliChen,HuiZhao,Tongfeng Sulforaphane High glucose Hippocampus NF-E2-related factor 2 Nuclear factor-κΒ Abstract Background: Oxidative stress is the hallmark of diabetic encephalopathy, which may be caused by hyperglycaemic toxicity. We aimed to discover pharmacologic targets to restore redox homeostasis. We identified the transcription factor Nrf2 as such a target. Methods: HT22 cells were cultured in 25 or 50 mM D-glucose with various concentrations of sulforaphane (SFN) (from 1.25 to 5.0 μΜ). Cell viability was tested with the Cell Counting Kit-8 assay. Reactive oxygen species (ROS) production was detected with an inverted fluorescence microscope using the dichlorodihydrofluorescein-diacetate fluorescent probe. The expression of NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1) and nuclear factor-κΒ (NF-κΒ) at the mRNA and protein levels was detected by reverse transcription quantitative polymerase chain reaction and western blotting. Result: We found that a high glucose concentration (50 mM) increased the generation of ROS, downregulated the expression of Nrf2/HO-1 and upregulated the expression of NF-κΒ. Moreover, HT22 cell viability significantly decreased after culture in high-glucose medium for 24, 48 and 72 h, whereas the activation of the Nrf2/HO-1 pathway using a pharmacological Nrf2 activator abrogated this high-glucose-induced toxicity. Conclusion: This study suggests that the activation of the Nrf2-ARE signalling pathway might be a therapeutic target for the treatment of diabetic encephalopathy.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.52 20192019-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100249en10.1186/s40659-019-0258-z
institution Scielo Chile
collection Scielo Chile
language English
topic Sulforaphane
High glucose
Hippocampus
NF-E2-related factor 2
Nuclear factor-κΒ
spellingShingle Sulforaphane
High glucose
Hippocampus
NF-E2-related factor 2
Nuclear factor-κΒ
Zhao,Jiangpei
Liu,Lerong
Li,Xia
Zhang,Lingxiao
Lv,Jing
Guo,Xueli
Chen,Hui
Zhao,Tongfeng
Neuroprotective effects of an Nrf2 agonist on high glucose-induced damage in HT22 cells
description Abstract Background: Oxidative stress is the hallmark of diabetic encephalopathy, which may be caused by hyperglycaemic toxicity. We aimed to discover pharmacologic targets to restore redox homeostasis. We identified the transcription factor Nrf2 as such a target. Methods: HT22 cells were cultured in 25 or 50 mM D-glucose with various concentrations of sulforaphane (SFN) (from 1.25 to 5.0 μΜ). Cell viability was tested with the Cell Counting Kit-8 assay. Reactive oxygen species (ROS) production was detected with an inverted fluorescence microscope using the dichlorodihydrofluorescein-diacetate fluorescent probe. The expression of NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1) and nuclear factor-κΒ (NF-κΒ) at the mRNA and protein levels was detected by reverse transcription quantitative polymerase chain reaction and western blotting. Result: We found that a high glucose concentration (50 mM) increased the generation of ROS, downregulated the expression of Nrf2/HO-1 and upregulated the expression of NF-κΒ. Moreover, HT22 cell viability significantly decreased after culture in high-glucose medium for 24, 48 and 72 h, whereas the activation of the Nrf2/HO-1 pathway using a pharmacological Nrf2 activator abrogated this high-glucose-induced toxicity. Conclusion: This study suggests that the activation of the Nrf2-ARE signalling pathway might be a therapeutic target for the treatment of diabetic encephalopathy.
author Zhao,Jiangpei
Liu,Lerong
Li,Xia
Zhang,Lingxiao
Lv,Jing
Guo,Xueli
Chen,Hui
Zhao,Tongfeng
author_facet Zhao,Jiangpei
Liu,Lerong
Li,Xia
Zhang,Lingxiao
Lv,Jing
Guo,Xueli
Chen,Hui
Zhao,Tongfeng
author_sort Zhao,Jiangpei
title Neuroprotective effects of an Nrf2 agonist on high glucose-induced damage in HT22 cells
title_short Neuroprotective effects of an Nrf2 agonist on high glucose-induced damage in HT22 cells
title_full Neuroprotective effects of an Nrf2 agonist on high glucose-induced damage in HT22 cells
title_fullStr Neuroprotective effects of an Nrf2 agonist on high glucose-induced damage in HT22 cells
title_full_unstemmed Neuroprotective effects of an Nrf2 agonist on high glucose-induced damage in HT22 cells
title_sort neuroprotective effects of an nrf2 agonist on high glucose-induced damage in ht22 cells
publisher Sociedad de Biología de Chile
publishDate 2019
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100249
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AT liulerong neuroprotectiveeffectsofannrf2agonistonhighglucoseinduceddamageinht22cells
AT lixia neuroprotectiveeffectsofannrf2agonistonhighglucoseinduceddamageinht22cells
AT zhanglingxiao neuroprotectiveeffectsofannrf2agonistonhighglucoseinduceddamageinht22cells
AT lvjing neuroprotectiveeffectsofannrf2agonistonhighglucoseinduceddamageinht22cells
AT guoxueli neuroprotectiveeffectsofannrf2agonistonhighglucoseinduceddamageinht22cells
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AT zhaotongfeng neuroprotectiveeffectsofannrf2agonistonhighglucoseinduceddamageinht22cells
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