Yanhong Li1, Jian Fang1, Zhanye Zhou2, Qiyu Zhou3, Shibin Sun2, Zhikai Jin2, Ziming Xi1, Jianshe Wei4. 1. Department of General Medicine, The First Affiliated Hospital of Henan University, Kaifeng, Henan, China. 2. Department of General Medicine, Henan University, Kaifeng, Henan, China. 3. Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, China. 4. Department of General Medicine, Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng, Henan, China.
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.
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 PDrats. 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 PDrats. Downregulated BACE1-AS repressed apoptosis and oxidative stress injury in the substantia nigra neurons of PDrats. 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 PDrats by upregulating miR-34b-5p and downregulating BACE1.
Authors: Shubhra Acharya; Antonio Salgado-Somoza; Francesca Maria Stefanizzi; Andrew I Lumley; Lu Zhang; Enrico Glaab; Patrick May; Yvan Devaux Journal: Int J Mol Sci Date: 2020-09-06 Impact factor: 5.923