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Berberine Attenuates MPP+-Induced Neuronal Injury by Regulating LINC00943/miR-142-5p/KPNA4/NF-κB Pathway in SK-N-SH Cells

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Abstract

Berberine plays a neuro-protective role in neurodegenerative diseases, including Parkinson’s disease (PD). Long non-coding RNAs (lncRNAs) play critical roles in PD pathogenesis. The purpose of this study was to investigate whether LINC00943 was involved in the role of berberine in PD. 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) or 1-methyl-4-phenyl pyridine (MPP+) were used to construct PD mouse and cell models, respectively. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2’-deoxyuridine (Edu) assays. Inflammation and cell apoptosis were assessed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. Quantitative real-time PCR (qRT-PCR) was employed to test the expression of LINC00943, microRNA (miR)-142-5p, and karyopherin subunit alpha 4 (KPNA4) mRNA. The protein levels of NF-κB pathway-related markers and KPNA4 were measured by western blot. Oxidative stress level was assessed by corresponding kits. The interaction between miR-142-5p and LINC00943 or KPNA4 was determined via dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Berberine inhibited MPP+-induced injury in SK-N-SH cells by promoting cell proliferation and suppressing inflammation, apoptosis, and oxidative injury. LINC00943 and KPNA4 were upregulated and miR-142-5p was downregulated in PD mouse and cell models. LINC00943 (or KPNA4) overexpression or miR-142-5p inhibition abated the neuro-protective role of berberine in PD cell model. Moreover, miR-142-5p was a target of LINC00943, and KPNA4 could specially bind to miR-142-5p. Additionally, berberine inhibited NF-κB pathway by regulating LINC00943/miR-142-5p/KPNA4 axis. Berberine protected SK-N-SH cell from MPP+-induced neuronal damage via regulating LINC00943/miR-142-5p/KPNA4/NF-κB pathway, highlighting novel evidence for the neuro-protective role of berberine in PD.

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Author notes

  1. Xueqin Li, Yan Su and Na Li contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, Shandong, China

    Xueqin Li

  2. Medical Service, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, Shandong, China

    Yan Su

  3. Department of Rehabilitation, The People’s Hospital of Qingdao Shinan District, Qingdao, 266002, Shandong, China

    Na Li

  4. Tianshan Community Clinic, The People’s Hospital of Qingdao Shinan District, Qingdao, 266002, China

    Feng-Ru Zhang

  5. Department of Geriatrics, Yantai Affiliated Hospital of Binzhou Medical University, No.717, Jinbu Street, MuPing District, Yantai, 264100, Shandong, China

    Nan Zhang

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  1. Xueqin Li
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Li, X., Su, Y., Li, N. et al. Berberine Attenuates MPP+-Induced Neuronal Injury by Regulating LINC00943/miR-142-5p/KPNA4/NF-κB Pathway in SK-N-SH Cells. Neurochem Res 46, 3286–3300 (2021). https://doi.org/10.1007/s11064-021-03431-w

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  • DOI: https://doi.org/10.1007/s11064-021-03431-w

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