Downregulation of lncRNA BACE1-AS improves dopamine-dependent oxidative stress in rats with Parkinson's disease by upregulating microRNA-34b-5p and downregulating BACE1. Issue 10 (18th May 2020)

• Record Type: Journal Article
• Authors: Li, Yanhong; Fang, Jian; Zhou, Zhanye; Zhou, Qiyu; Sun, Shibin; Jin, Zhikai; Xi, Ziming; Wei, Jianshe
• Is Part Of: Cell cycle. Volume 19:Issue 10(2020)
• Page Start: 1158
• Page End: 1171
• Publication Date: 2020-05-18
• Subjects: Long noncoding RNA BACE1-AS -- Parkinson's disease -- MicroRNA-34b-5p -- BACE1 -- iNOS -- dopaminergic neurons; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2020.1749447
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Objective : 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. Methods : 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. Results : 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. Conclusion : 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.