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Regulation of AKT/AMPK signaling, autophagy and mitigation of apoptosis in Rutin-pretreated SH-SY5Y cells exposed to MPP +
Metabolic Brain Disease ( IF 3.2 ) Pub Date : 2020-11-04 , DOI: 10.1007/s11011-020-00641-z
Adaze Bijou Enogieru 1, 2 , William Haylett 3 , Donavon Charles Hiss 1 , Okobi Eko Ekpo 1
Affiliation  

Accumulating evidence suggest that apoptosis, autophagy and dysregulation of signaling pathways are common mechanisms involved in Parkinson’s disease (PD) pathogenesis, and thus development of therapeutic agents targeting these mechanisms may be useful for the treatment of this disease. Although rutin (a bioflavonoid) is reported to have pharmacological benefits such as antioxidant, anti-inflammatory and antitumor activities, there are very few reports on the activity of this compound in 1-methyl-4-phenylpyridinium (MPP+)-induced PD models. Accordingly, we investigated the effects of rutin on apoptosis, autophagy and cell signaling markers (AKT/AMPK) in SH-SY5Y cells exposed to MPP+. Results show reduced changes in nuclear morphology and mitigation of caspase 3/7 and 9 activities in rutin pre-treated cells exposed to MPP+. Likewise, rutin regulated cell signaling pathways (AKT/AMPK) and significantly decreased protein expression levels of cleaved PARP, cytochrome c, LC3-II and p62. Also, rutin significantly increased protein expression levels of full-length caspase 3 in SH-SY5Y cells treated with MPP+. Transmission electron microscope (TEM) images demonstrated a reduction in autophagosomes in rutin-pretreated SH-SY5Y cells exposed to MPP+. These results provide experimental support for rutin’s neuroprotective activity against MPP+-induced toxicity in SH-SY5Y cells, which is as a promising therapeutic agent for clinical trials in humans.



中文翻译:

暴露于 MPP + 芦丁预处理的 SH-SY5Y 细胞中 AKT/AMPK 信号、自噬和细胞凋亡的调节

越来越多的证据表明,细胞凋亡、自噬和信号通路失调是参与帕金森病 (PD) 发病机制的常见机制,因此开发针对这些机制的治疗剂可能有助于治疗这种疾病。尽管据报道芦丁(一种生物类黄酮)具有抗氧化、抗炎和抗肿瘤活性等药理作用,但很少有关于该化合物在 1-甲基-4-苯基吡啶鎓(MPP +)诱导的 PD 模型中的活性的报道. 因此,我们研究了芦丁对暴露于 MPP + 的SH-SY5Y 细胞凋亡、自噬和细胞信号标志物 (AKT/AMPK) 的影响。. 结果显示,在暴露于 MPP + 的芦丁预处理细胞中,核形态变化减少,半胱天冬酶 3/7 和 9 活性降低。同样,芦丁调节细胞信号通路 (AKT/AMPK) 并显着降低裂解的 PARP、细胞色素 c、LC3-II 和 p62 的蛋白质表达水平。此外,芦丁显着增加了用 MPP +处理的 SH-SY5Y 细胞中全长 caspase 3 的蛋白质表达水平。透射电子显微镜 (TEM) 图像表明暴露于 MPP + 的芦丁预处理的 SH-SY5Y 细胞中的自噬体减少。这些结果为芦丁对 MPP +的神经保护活性提供了实验支持-在 SH-SY5Y 细胞中诱导毒性,这是一种有前途的人类临床试验治疗剂。

更新日期:2020-11-04
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