Baicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death

Abstract 6-OHDA plus ascorbic acid (AA) has long been used to induce Parkinson’s disease in rodents, while only 6-OHDA is commonly used to induce cell damage in cellular PD models. AA was believed to act as an anti-oxidant to prevent the degradation of 6-OHDA; however, some studies suggested that AA...

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Autores principales: Sheng-Fang Wang, Liang-Feng Liu, Ming-Yue Wu, Cui-Zan Cai, Huanxing Su, Jieqiong Tan, Jia-Hong Lu, Min Li
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/43af75dc2e204c9ca4ab9c1fd1ec99ca
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spelling oai:doaj.org-article:43af75dc2e204c9ca4ab9c1fd1ec99ca2021-12-02T15:04:54ZBaicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death10.1038/s41598-017-07142-72045-2322https://doaj.org/article/43af75dc2e204c9ca4ab9c1fd1ec99ca2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07142-7https://doaj.org/toc/2045-2322Abstract 6-OHDA plus ascorbic acid (AA) has long been used to induce Parkinson’s disease in rodents, while only 6-OHDA is commonly used to induce cell damage in cellular PD models. AA was believed to act as an anti-oxidant to prevent the degradation of 6-OHDA; however, some studies suggested that AA dramatically enhanced the selectivity and toxicity of 6-OHDA. To understand the mechanisms by which 6-OHDA/AA induces cell death, we established a 6-OHDA/AA cell toxicity model in human dopaminergic neuroblastoma SH-SY5Y cells. We confirmed that the toxicity of 6-OHDA was dramatically increased in the presence of AA, and the toxicity can be prevented by a flavonoid, baicalein. Mechanistically, our research reveals that 6-OHDA/AA induces cell death mainly through the interruption of intracellular calcium homeostasis, which leads to calpain activation and mitochondrial damage. Baicalein prevents 6-OHDA/AA-induced intracellular calcium elevation as well as consequent mitochondria damage. Taken together, our study confirms that 6-OHDA/AA is a more sensitive model for inducing neuronal lesion in vitro and reveals the central role of intracellular calcium in 6-OHDA/AA-induced cell death. Our studies further show that baicalein prevents 6-OHDA/AA-induced cell death by inhibiting intracellular calcium elevation.Sheng-Fang WangLiang-Feng LiuMing-Yue WuCui-Zan CaiHuanxing SuJieqiong TanJia-Hong LuMin LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sheng-Fang Wang
Liang-Feng Liu
Ming-Yue Wu
Cui-Zan Cai
Huanxing Su
Jieqiong Tan
Jia-Hong Lu
Min Li
Baicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death
description Abstract 6-OHDA plus ascorbic acid (AA) has long been used to induce Parkinson’s disease in rodents, while only 6-OHDA is commonly used to induce cell damage in cellular PD models. AA was believed to act as an anti-oxidant to prevent the degradation of 6-OHDA; however, some studies suggested that AA dramatically enhanced the selectivity and toxicity of 6-OHDA. To understand the mechanisms by which 6-OHDA/AA induces cell death, we established a 6-OHDA/AA cell toxicity model in human dopaminergic neuroblastoma SH-SY5Y cells. We confirmed that the toxicity of 6-OHDA was dramatically increased in the presence of AA, and the toxicity can be prevented by a flavonoid, baicalein. Mechanistically, our research reveals that 6-OHDA/AA induces cell death mainly through the interruption of intracellular calcium homeostasis, which leads to calpain activation and mitochondrial damage. Baicalein prevents 6-OHDA/AA-induced intracellular calcium elevation as well as consequent mitochondria damage. Taken together, our study confirms that 6-OHDA/AA is a more sensitive model for inducing neuronal lesion in vitro and reveals the central role of intracellular calcium in 6-OHDA/AA-induced cell death. Our studies further show that baicalein prevents 6-OHDA/AA-induced cell death by inhibiting intracellular calcium elevation.
format article
author Sheng-Fang Wang
Liang-Feng Liu
Ming-Yue Wu
Cui-Zan Cai
Huanxing Su
Jieqiong Tan
Jia-Hong Lu
Min Li
author_facet Sheng-Fang Wang
Liang-Feng Liu
Ming-Yue Wu
Cui-Zan Cai
Huanxing Su
Jieqiong Tan
Jia-Hong Lu
Min Li
author_sort Sheng-Fang Wang
title Baicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death
title_short Baicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death
title_full Baicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death
title_fullStr Baicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death
title_full_unstemmed Baicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death
title_sort baicalein prevents 6-ohda/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/43af75dc2e204c9ca4ab9c1fd1ec99ca
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AT liangfengliu baicaleinprevents6ohdaascorbicacidinducedcalciumdependentdopaminergicneuronalcelldeath
AT mingyuewu baicaleinprevents6ohdaascorbicacidinducedcalciumdependentdopaminergicneuronalcelldeath
AT cuizancai baicaleinprevents6ohdaascorbicacidinducedcalciumdependentdopaminergicneuronalcelldeath
AT huanxingsu baicaleinprevents6ohdaascorbicacidinducedcalciumdependentdopaminergicneuronalcelldeath
AT jieqiongtan baicaleinprevents6ohdaascorbicacidinducedcalciumdependentdopaminergicneuronalcelldeath
AT jiahonglu baicaleinprevents6ohdaascorbicacidinducedcalciumdependentdopaminergicneuronalcelldeath
AT minli baicaleinprevents6ohdaascorbicacidinducedcalciumdependentdopaminergicneuronalcelldeath
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