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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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) |
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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 |
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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 |
work_keys_str_mv |
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1718389012079575040 |