Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons
文献类型：期刊论文
| 作者 | Tao, Ling-xue; Huang, Xiao-tian; Chen, Yu-ting; Tang, Xi-can ; Zhang, Hai-yan
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| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2016-11 |
| 卷号 | 37期号:11页码:1391-1400 |
| 关键词 | Alzheimer's disease huperzine A iron reactive oxygen species mitochondria dysfunction acetylcholinesterase |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2016.78 |
| 文献子类 | Article |
| 英文摘要 | Aim: Iron dyshomeostasis is one of the primary causes of neuronal death in Alzheimer's disease (AD). Huperzine A (HupA), a natural inhibitor of acetylcholinesterase (AChE), is a licensed anti-AD drug in China and a nutraceutical in the United Sates. Here, we investigated the protective effects of HupA against iron overload-induced injury in neurons. Methods: Rat cortical neurons were treated with ferric ammonium citrate (FAC), and cell viability was assessed with MTT assays. Reactive oxygen species (ROS) assays and adenosine triphosphate (ATP) assays were performed to assess mitochondrial function. The labile iron pool (LIP) level, cytosolic-aconitase (c-aconitase) activity and iron uptake protein expression were measured to determine iron metabolism changes. The modified Ellman's method was used to evaluate AChE activity. Results: HupA significantly attenuated the iron overload-induced decrease in neuronal cell viability. This neuroprotective effect of HupA occurred concurrently with a decrease in ROS and an increase in ATP. Moreover, HupA treatment significantly blocked the upregulation of the LIP level and other aberrant iron metabolism changes induced by iron overload. Additionally, another specific AChE inhibitor, donepezil (Don), at a concentration that caused AChE inhibition equivalent to that of HupA negatively, influenced the aberrant changes in ROS, ATP or LIP that were induced by excessive iron. Conclusion: We provide the first demonstration of the protective effects of HupA against iron overload-induced neuronal damage. This beneficial role of HupA may be attributed to its attenuation of oxidative stress and mitochondrial dysfunction and elevation of LIP, and these effects are not associated with its AChE-inhibiting effect. |
| WOS关键词 | ALZHEIMERS-DISEASE ; NEURODEGENERATIVE DISORDERS ; INTRACEREBRAL HEMORRHAGE ; REGULATORY PROTEINS ; LIPID-PEROXIDATION ; AMYLOID-BETA ; CELL-DEATH ; BRAIN ; POOL ; MITOCHONDRIA |
| 资助项目 | National Natural Science Foundation of China[81522045] ; National Natural Science Foundation of China[31400932] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000387755900001 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275833]  |
| 专题 | 药理学第二研究室 |
| 通讯作者 | Zhang, Hai-yan |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tao, Ling-xue,Huang, Xiao-tian,Chen, Yu-ting,et al. Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons[J]. ACTA PHARMACOLOGICA SINICA,2016,37(11):1391-1400. |
| APA | Tao, Ling-xue,Huang, Xiao-tian,Chen, Yu-ting,Tang, Xi-can,&Zhang, Hai-yan.(2016).Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons.ACTA PHARMACOLOGICA SINICA,37(11),1391-1400. |
| MLA | Tao, Ling-xue,et al."Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons".ACTA PHARMACOLOGICA SINICA 37.11(2016):1391-1400. |
入库方式： OAI收割
来源：上海药物研究所
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