PIAS3 通过诱导 STAT3 相关的 STAT3/Nestin/Nrf2/HO-1 通路抑制阿尔茨海默病细胞模型中的损伤。

PIAS3 suppresses damage in an Alzheimer's disease cell model by inducing the STAT3-associated STAT3/Nestin/Nrf2/HO-1 pathway.

机构信息

Department of Geriatrics Neurology, the Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi, People's Republic of China.

出版信息

Mol Med. 2021 Nov 27;27(1):150. doi: 10.1186/s10020-021-00410-3.

BACKGROUND

Alzheimer's disease (AD), the most common form of dementia, is caused by the degeneration of the central nervous system (CNS). A previous study reported that signal transducer and activator of transcription 3 (STAT3) is activated during AD development; nonetheless, the related mechanism remains unknown. Thus, this study used a cell model to explore whether and how the protein inhibitor of activated STAT3 (PIAS3) is involved in AD development.

METHODS

Cerebrospinal fluid (CSF) specimens of 30 patients with AD and 10 normal participants were included in this study. SH-SY5Y cells were used to constructed AD model. Relevant indices were then detected and analyzed.

RESULTS

The results showed that compared with the control group, PIAS3 expression was substantially decreased in patients with AD and amyloid beta (Aβ)-treated SH-SY5Y cells. PIAS3 overexpression was able to reverse the detrimental effects of Aβ treatment on cell survival and growth. Further, it could also ameliorate apoptosis and oxidative stress in Aβ-treated SH-SY5Y cells. Additionally, PIAS3 was shown to reduce the activated form of STAT3 and increase the activity of the downstream Nestin/nuclear factor erythroid 2-related factor/heme oxygenase-1 pathway.

CONCLUSIONS

STAT3 reactivation by colivelin treatment negated the influence of PIAS3 on the survival, growth, apoptosis, and oxidative stress of Aβ-treated SH-SY5Y cells.

背景

阿尔茨海默病（AD）是最常见的痴呆症形式，由中枢神经系统（CNS）退化引起。先前的一项研究报告称，信号转导子和转录激活子 3（STAT3）在 AD 发展过程中被激活；然而，相关机制尚不清楚。因此，本研究使用细胞模型来探讨蛋白抑制剂激活 STAT3（PIAS3）是否以及如何参与 AD 发展。

方法

纳入 30 例 AD 患者和 10 例正常参与者的脑脊液（CSF）标本。使用 SH-SY5Y 细胞构建 AD 模型。然后检测和分析相关指标。

结果

结果表明，与对照组相比，AD 患者和 Aβ处理的 SH-SY5Y 细胞中 PIAS3 的表达显著降低。PIAS3 的过表达能够逆转 Aβ处理对细胞存活和生长的不利影响。此外，它还可以改善 Aβ处理的 SH-SY5Y 细胞中的细胞凋亡和氧化应激。此外，PIAS3 被证明可以减少激活形式的 STAT3 并增加下游 Nestin/核因子红细胞 2 相关因子/血红素加氧酶-1 通路的活性。