Downregulation of lncRNA BACE1-AS improves dopamine-dependent oxidative stress in rats with Parkinson’s disease by upregulating microRNA-34b-5p and downregulating BACE1
Autor: | Jianshe Wei, Ziming Xi, Yanhong Li, Zhanye Zhou, Qiyu Zhou, Zhikai Jin, Jian Fang, Shibin Sun |
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Rok vydání: | 2020 |
Předmět: |
Male
Expression of Concern 0301 basic medicine Parkinson's disease Genetic Vectors BACE1-AS Down-Regulation Nitric Oxide Synthase Type II Apoptosis Disease Biology medicine.disease_cause Hydroxydopamines 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Dopamine mental disorders medicine Animals Aspartic Acid Endopeptidases RNA Antisense Parkinson Disease Secondary Molecular Biology Dopaminergic Neurons Cell Biology medicine.disease Rats Up-Regulation Substantia Nigra Disease Models Animal MicroRNAs Oxidative Stress 030104 developmental biology 030220 oncology & carcinogenesis MicroRNA 34b Cancer research RNA Long Noncoding Amyloid Precursor Protein Secretases Oxidative stress Function (biology) Signal Transduction Developmental Biology medicine.drug |
Zdroj: | Cell Cycle |
ISSN: | 1551-4005 1538-4101 |
DOI: | 10.1080/15384101.2020.1749447 |
Popis: | bObjective/b: Long noncoding RNAs (lncRNAs) have already been proposed to function in Parkinson's disease (PD). However, the role of lncRNA BACE1-AS in PD has never been discussed. This study aims to examine the mechanism of BACE1-AS on oxidative stress injury of dopaminergic neurons in PD rats.bMethods/b: Rat models of PD were established through the injection of 6-hydroxydopamine. The rotation of rats was induced by intraperitoneal injection of apomorphine, and number of rotations per minute was detected. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), glutamic acid (Glu), dopamine (DA), tyrosine hydroxylase (TH), α-synuclein and inducible nitric oxide synthase (iNOS) in the substantia nigra of rats in each group were detected. Apoptosis and pathological changes in the substantia nigra were also observed. BACE1-AS, miR-34b-5p, BACE1, Bax and Bcl-2 expression in the substantia nigra were detected. The binding of BACE1-AS and miR-34b-5p and the targeting relationship of miR-34b-5p and BACE1 were further determined.bResults/b: Downregulated BACE1-AS reduced iNOS, α-synuclein and Glu levels and elevated DA and TH levels in the substantia nigra of PD rats. Downregulated BACE1-AS repressed apoptosis and oxidative stress injury in the substantia nigra neurons of PD rats. BACE1-AS specifically bound to miR-34b-5p. BACE1 was a direct target gene of miR-34b-5p.bConclusion/b: Collectively, our study reveals that downregulation of lncRNA BACE1-AS inhibits iNOS activation in the substantial nigra and improve oxidative stress injury in PD rats by upregulating miR-34b-5p and downregulating BACE1. |
Databáze: | OpenAIRE |
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