MiR-9-5p inhibits mitochondrial damage and oxidative stress in AD cell models by targeting GSK-3β

ABSTRACT

This study aims to investigate the effects and underlying mechanisms of overexpression microRNA-9-5p (miR-9-5p) on the Aβ-induced mouse hippocampal neuron cell line HT22. Different concentrations of Aβ_25-35 (10, 20, 40, 80, and 160 μM) treatment were used to establish AD model in HT22 cells. The CCK-8 assay was used to measure the cell viability. The mRNA expression levels of miR-9-5p and glycogen synthase kinase-3β (GSK-3β) were determined by RT-qPCR. HT22 cell apoptosis was analyzed flow cytometry. MiR-9-5p was down-regulated in Aβ_25-35-induced HT22 cells. GSK-3β is a functional target for miR-9-5p. MiR-9-5p overexpression inhibited Aβ_25-35-induced mitochondrial dysfunction, cell apoptosis, and oxidative stress by regulating GSK-3β expression in HT22 cells. Furthermore, through targeting GSK-3β, overexpression of miR-9-5p partly activated nuclear factor Nrf2/Keap1 signaling, including part increases of Nrf2, HO-1, SOD-1, GCLC expression and slight decrease of Keap1 expression. Our results showed miR-9-5p may play a powerful role in the pathogenesis of AD.

GRAPHICAL ABSTRACT

MiR-9-5p inhibits mitochondrial damage, oxidative stress, and cell apoptosis in Aβ25-35-induced HT22 cells by targeting GSK-3β/Nrf2/Keap1 signaling.

KEYWORDS:

• MiR-9-5p
• glycogen Synthase kinase-3β
• mitochondrial dysfunction
• cell apoptosis
• Alzheimer’s disease

Authors’ contributions

Sen Cui, Junli Liu, Xiaoqin Zuo, and Jixiang Han conceived and designed the experiments.

Junli Liu, Xiaoqin Zuo, Jixiang Han, Qingxiang Dai, Huining Xu, and Ying Liu performed the experiments.

Xiaoqin Zuo, Jixiang Han, Qingxiang Dai, Huining Xu, and Ying Liu analyzed the data.

Sen Cui, Junli Liu, Xiaoqin Zuo, and Jixiang Han wrote the paper.

All authors have read and approved the final version of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Science and Technology Innovation Ability Promotion Project of Qinghai Province of China [No.2017-ZJ-771].