An optically active isochroman-2H-chromene conjugate potently suppresses neuronal oxidative injuries associated with the PI3K/Akt and MAPK signaling pathways
文献类型：期刊论文
| 作者 | Tao, Ling-xue1; Ji, Sha-sha1; Szaloki, Dora2; Kovacs, Tibor2; Mandi, Attila2; Antus, Sandor2; Ding, Xun1; Kurtan, Tibor2; Zhang, Hai-yan1
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2020-05-11 |
| 页码 | 9 |
| 关键词 | neurodegeneration oxidative stress apoptosis MAPK pathway PI3K Akt pathway SH-SY5Y neuroblastoma cells |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-020-0391-9 |
| 通讯作者 | Kovacs, Tibor(kurtan.tibor@science.unideb.hu) ; Zhang, Hai-yan(hzhang@simm.ac.cn) |
| 英文摘要 | Increasing evidence suggests that the use of potent neuroprotective agents featured with novel pharmacological mechanism would offer a promising strategy to delay or prevent the progression of neurodegeneration. Here, we provide the first demonstration that the chiral nonracemic isochroman-2H-chromene conjugate JE-133, a novel synthetic 1,3-disubstituted isochroman derivative, possesses superior neuroprotective effect against oxidative injuries. Pretreatment with JE-133 (1-10 mu M) concentration-dependently prevented H2O2-induced cell death in SH-SY5Y neuroblastoma cells and rat primary cortical neurons. Pretreatment with JE-133 significantly alleviated H2O2-induced apoptotic changes. These protective effects could not be simply attributed to the direct free radical scavenging as JE-133 had moderate activity in reducing DPPH free radical. Further study revealed that pretreatment with JE-133 (10 mu M) significantly decreased the phosphorylation of MAPK pathway proteins, especially ERK and P38, in the neuronal cells. In addition, blocking PI3K/Akt pathway using LY294002 partially counteracted the cell viability-enhancing effect of JE-133. We conclude that JE-133 exerts neuroprotection associated with dual regulative mechanisms and consequently activating cell survival and inhibiting apoptotic changes, which may provide important clues for the development of effective neuroprotective drug lead/candidate. |
| WOS关键词 | PEROXIDE-INDUCED APOPTOSIS ; HYDROGEN-PEROXIDE ; H2O2-INDUCED APOPTOSIS ; SH-SY5Y CELLS ; PC12 CELLS ; ALZHEIMERS-DISEASE ; STRESS ; PROTECTS ; DEATH ; ANTIOXIDANT |
| 资助项目 | National Natural Science Foundation of China[81703507] ; National Natural Science Foundation of China[81872859] ; National Natural Science Foundation of China[81522045] ; EU ; European Regional Development Fund[GINOP-2.3.2-15-2016-00008] ; National Research Development and Innovation Office[K-120181] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000531761600001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/280201]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Kovacs, Tibor; Zhang, Hai-yan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Univ Debrecen, Dept Organ Chem, POB 400, H-4002 Debrecen, Hungary |
| 推荐引用方式 GB/T 7714 | Tao, Ling-xue,Ji, Sha-sha,Szaloki, Dora,et al. An optically active isochroman-2H-chromene conjugate potently suppresses neuronal oxidative injuries associated with the PI3K/Akt and MAPK signaling pathways[J]. ACTA PHARMACOLOGICA SINICA,2020:9. |
| APA | Tao, Ling-xue.,Ji, Sha-sha.,Szaloki, Dora.,Kovacs, Tibor.,Mandi, Attila.,...&Zhang, Hai-yan.(2020).An optically active isochroman-2H-chromene conjugate potently suppresses neuronal oxidative injuries associated with the PI3K/Akt and MAPK signaling pathways.ACTA PHARMACOLOGICA SINICA,9. |
| MLA | Tao, Ling-xue,et al."An optically active isochroman-2H-chromene conjugate potently suppresses neuronal oxidative injuries associated with the PI3K/Akt and MAPK signaling pathways".ACTA PHARMACOLOGICA SINICA (2020):9. |
入库方式： OAI收割
来源：上海药物研究所
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