文章基本信息

标题：Genistein protects against Aβ 25–35 induced apoptosis of PC12 cells through JNK signaling and modulation of Bcl-2 family messengers
本地全文：下载
作者：Fuling You ; Qiao Li ; Guifang Jin 等
期刊名称：BMC Neuroscience
印刷版ISSN：1471-2202
电子版ISSN：1471-2202
出版年度：2017
卷号：18
期号：1
页码：12
DOI：10.1186/s12868-016-0329-9
语种：English
出版社：BioMed Central
摘要：Background Deposition of aggregated amyloid beta (Aβ) protein is hallmark of Alzheimer’s disease, leading to dysfunction and apoptosis of neurons. The isoflavone phytoestrogen compound genistein (Gen) exerts a significant protective effect against Aβ_25–35 induced neurotoxicity and mitochondrial damage in rat pheochromocytoma (PC12) cells. However, the mechanisms underlying Gen’s rescue remain elusive. Therefore we endeavored to research further the molecular mechanisms underlying Gen’s inhibition of Aβ_25–35 induced apoptosis of neurons. Results We found that Gen dramatically suppressed the activation by Aβ_25–35 of p-c-Jun N-terminal kinase (p-JNK), and also inhibited the JNK-dependent decreased of Bcl-w and increased of Bim. Furthermore, Gen significantly reduced the cytoplasmic concentrations of cytochrome c and Smac protein as well as caspase-3 activity. Additionally, pretreatment with JNK inhibitor SP600125 effectively suppressed Aβ_25–35 induced PC12 cell cytotoxicity. Conclusion Taken together, the results suggested that Gen protects PC12 cells from Aβ_25–35 induced neurotoxicity by interfering with p-JNK activation, thus attenuating the JNK-dependent apoptosis through the mitochondrial pathway. These findings constitute novel insights into the pathway for Aβ_25–35 toxicity, and the neuroprotective action of Gen.
关键词：Alzheimer’s disease ; Aβ 25–35 ; Apoptosis ; Genistein ; JNK ; Bcl-2