Neuroprotective effects of silk fibroin hydrolysate against Aβ25–35 induced cytotoxicity in SH-SY5Y cells and primary hippocampal neurons by regulating ROS inactivation of PP2A

Neuroprotective effects of silk fibroin hydrolysate against Aβ25–35 induced cytotoxicity in SH-SY5Y cells and primary hippocampal neurons by regulating ROS inactivation of PP2A
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丝素蛋白水解物通过调节 PP2A ROS 失活对 A beta(25-35) 诱导的 SH-SY5Y 细胞和原代海马神经元细胞毒性的神经保护作用

DOI:
10.1016/j.jff.2018.03.032
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发表时间:
2018-06
影响因子:
5.6
通讯作者:
Xiang-Dong Gao
Xiang-Dong Gao
中科院分区:
农林科学2区
文献类型:
--
作者:
Zheng Xu;Song Chen;Ying Wang;Su-Ting Chen;Wen-Bing Yao;Xiang-Dong Gao

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丝素蛋白(SF)被广泛用作生物医学材料,丝素蛋白水解产物(SFH)显示出许多活性。本研究旨在探讨SFH对a - β25 - 35诱导的SH-SY5Y细胞和海马原代神经元细胞毒性的神经保护作用及其可能的机制。结果表明,SFH可提高a - β25 - 35损伤海马SH-SY5Y和原代神经元的活力。经SFH处理后,a - β25 - 35诱导的线粒体膜电位降低,细胞凋亡增加。进一步的研究表明,SFH的有益作用可能是由于其对活性氧(ROS)的干扰。SFH通过抑制a β25 - 35诱导的ROS抑制Ser/Thr蛋白磷酸酶2A (PP2A)的磷酸化,进而抑制MAPKs的激活和tau的过度磷酸化,保护SH-SY5Y细胞和原代神经元免受a β25 - 35诱导的损伤。SFH有可能成为干预AD的营养保健品。
Silk fibroin (SF) has been widely used as biomedical materials and the hydrolysate form of SF (SFH) has shown many activities. The purpose of the current study was to explore the neuroprotective effects of SFH against Aβ25–35-induced cytotoxicity in SH-SY5Y cells and primary hippocampal neurons and the possible mechanism. The results showed that SFH could improve the viabilities of SH-SY5Y and primary hippocampal neurons injured by Aβ25–35. The lowered mitochondrial membrane potential and increased cell apoptosis induced by Aβ25–35were recovered after SFH treatment. Further study indicated that the beneficial effects of SFH were likely due to its interference with reactive oxygen species (ROS). SFH inhibited the phosphorylation of Ser/Thr protein phosphatase 2A (PP2A) by suppressing Aβ25–35-induced ROS, and then suppressed the activation of MAPKs and tau hyperphosphorylation, and protected SH-SY5Y cells and primary neurons from Aβ25–35-induced damages. SFH has the potential to be a nutraceutical for AD intervention.
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