Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H₂O₂-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway.
Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H₂O₂-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway.
复制标题
硫酸化杂多糖通过影响 PI3K/Akt 信号通路保护 SH-SY5Y 细胞免受 H2O2 诱导的细胞凋亡
DOI：
10.3390/md15040110
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发表时间：
2017-04-06
期刊：
影响因子：
5.4
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Wang J;Liu H;Zhang X;Li X;Geng L;Zhang H;Zhang Q
帕金森病（Parkinson's disease，PD）是最常见的神经退行性疾病之一。最近的研究表明，硫酸化杂多糖（UF）防止发展中的PD。然而，UF如何抑制神经元死亡的详细机制尚未完全阐明。我们使用人多巴胺能神经母细胞瘤SH-SY 5 Y细胞作为PD模型研究UF的细胞保护机制。UF以剂量依赖性方式阻止H2 O2诱导的SH-SY 5 Y细胞凋亡。对PI 3 K/Akt上游通路的检查显示，UF预处理的细胞显示Akt、PI 3 K和TrkA的相对密度降低，Akt、PI 3 K和NGF的磷酸化增加; PI 3 K抑制剂LY 294002部分阻止了这种作用。对PI 3 K/Akt下游通路的检查显示，在UF处理的细胞中，凋亡相关标志物Bax、p53、CytC和GSK 3 β的表达增加，Bcl-2的表达减少。UF处理的细胞也表现出caspase-3、caspase-8和caspase-9活性降低，从而诱导细胞凋亡。我们的研究结果表明，UF影响PI 3 K/Akt通路，以及下游信号。因此，UF介导的PI 3 K/Akt活化可能为与氧化损伤相关的神经退行性疾病提供新的潜在治疗策略。这些发现有助于更好地理解UF在PD治疗中的关键作用。
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of UF using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. UF prevented H2O2-induced apoptotic cell death in SH-SY5Y cells in a dose-dependent manner. An examination of the PI3K/Akt upstream pathway revealed that UF-pretreated cells showed a decreased relative density of Akt, PI3K, and TrkA, and increased the phosphorylation of Akt, PI3K, and NGF; the PI3K inhibitor, LY294002, partially prevented this effect. An examination of the PI3K/Akt downstream pathway revealed the increased expression of the apoptosis-associated markers Bax, p53, CytC, and GSK3β, and the decreased expression of Bcl-2 in UF-treated cells. UF-treated cells also exhibited decreased caspase-3, caspase-8, and caspase-9 activities, which induced cell apoptosis. Our results demonstrate that UF affect the PI3K/Akt pathway, as well as downstream signaling. Therefore, the UF-mediated activation of PI3K/Akt could provide a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury. These findings contribute to a better understanding of the critical roles of UF in the treatment of PD.