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D2/D3受体激动剂罗匹尼罗通过抑制半胱天冬酶和JNK依赖的途径保护多巴胺能细胞系免受鱼藤酮诱导的凋亡。

D2/D3 receptor agonist ropinirole protects dopaminergic cell line against rotenone-induced apoptosis through inhibition of caspase- and JNK-dependent pathways.

作者信息

Chen Sheng, Zhang Xiaojie, Yang Dehua, Du Yunlan, Li Liang, Li Xuping, Ming Ming, Le Weidong

机构信息

Department of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.

出版信息

FEBS Lett. 2008 Mar 5;582(5):603-10. doi: 10.1016/j.febslet.2008.01.028. Epub 2008 Jan 31.

Abstract

Ropinirole, a D2/D3 receptor agonist has been reported to have neuroprotective effects. We showed that ropinirole can prevent rotenone-induced apoptosis in dopaminergic cell line SH-SY5Y through D3 receptor. We found that ropinirole can block the rotenone-induced phosphorylation of JNK, P38 and p-c-Jun, but promote the phosphorylation of ERK1/2. Furthermore, we demonstrated that ropinirole can reduce the rotenone-induced cleavages of caspase 9, caspase 3 and PARP and elevate the expression of anti-apoptotic proteins of p-Akt and bcl-2. These results provide a basis for neuroprotection by this drug for the treatment of Parkinson disease.

摘要

罗匹尼罗是一种D2/D3受体激动剂,据报道具有神经保护作用。我们发现罗匹尼罗可通过D3受体预防鱼藤酮诱导的多巴胺能细胞系SH-SY5Y凋亡。我们发现罗匹尼罗可阻断鱼藤酮诱导的JNK、P38和p-c-Jun磷酸化,但促进ERK1/2磷酸化。此外,我们证明罗匹尼罗可减少鱼藤酮诱导的半胱天冬酶9、半胱天冬酶3和PARP的裂解,并提高抗凋亡蛋白p-Akt和bcl-2的表达。这些结果为该药物治疗帕金森病的神经保护作用提供了依据。

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