Liang Zhang1, Jingzhong Wang1, Qin Liu1, Zhiqiang Xiao2, Quande Dai3. 1. The Stroke Unit, The First People's Hospital of Shangqiu, Shangqiu City, 476100, Henan Province, PR China. 2. Department of Neurosurgery, The First People's Hospital of Shangqiu, Shangqiu City, 476100, Henan Province, PR China. 3. The Stroke Unit, The First People's Hospital of Shangqiu, Shangqiu City, 476100, Henan Province, PR China. Electronic address: daiquande@protonmail.com.
Abstract
BACKGROUND: Long noncoding RNAs (lncRNAs) have been defined as critical regulators of various human diseases. However, the functions of lncRNAs in Parkinson's disease (PD) have not yet been elucidated. In this study, we investigated the role of lncRNA AL049437 in PD and its underlying mechanism. METHODS: An in vivo model of PD was established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), while an in vitro model was created using N-methyl-4-phenylpyridinium (MPP+). Gene expression was evaluated using quantitative reverse transcriptase polymerase chain reaction and western blotting. The effects and mechanism of AL049437 in PD were explored using Cell Counting Kit-8 assay, flow cytometry, enzyme-linked immunosorbent assay, and 2',7'-dichlorodihydrofluorescein diacetate fluorescence assay. The interaction between AL049437, miR-205-5p, and mitogen-activated protein kinase 1 (MAPK1) was evaluated using luciferase reporter and RNA pull-down assays. RESULTS: The expression of AL049437 was upregulated, while that of miR-205-5p was downregulated in MPTP-induced PD mouse model and MPP+-treated SH-SY5Y cells. Silencing of AL049437 mitigated MPP+-induced neurotoxicity in SH-SY5Y cells, as demonstrated by increased cell viability and reduced cell apoptosis. Furthermore, silencing of AL049437 alleviated MPP+-induced neuroinflammation and oxidative stress, as indicated by the reduction in tumor necrosis factor-α and interleukin-6 levels and reactive oxygen species production. In addition, AL049437 was predominantly localized in the cytoplasm of SH-SY5Y cells and functioned as an miR-205-5p sponge. Moreover, MAPK1 was identified as a downstream target of miR-205-5p. Remarkably, the impact of AL049437 silencing on MPP+-induced neuronal damage could be blocked by miR-205-5p inhibition or MAPK1 overexpression. CONCLUSION: Knockdown of lncRNA AL049437 mitigates MPP+ -induced neuronal injury in SH-SY5Y cells by regulating the miR-205-5p/MAPK1 axis. Our research reveals a novel regulatory mechanism of AL049437 in PD progression.
BACKGROUND: Long noncoding RNAs (lncRNAs) have been defined as critical regulators of various human diseases. However, the functions of lncRNAs in Parkinson's disease (PD) have not yet been elucidated. In this study, we investigated the role of lncRNA AL049437 in PD and its underlying mechanism. METHODS: An in vivo model of PD was established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), while an in vitro model was created using N-methyl-4-phenylpyridinium (MPP+). Gene expression was evaluated using quantitative reverse transcriptase polymerase chain reaction and western blotting. The effects and mechanism of AL049437 in PD were explored using Cell Counting Kit-8 assay, flow cytometry, enzyme-linked immunosorbent assay, and 2',7'-dichlorodihydrofluorescein diacetate fluorescence assay. The interaction between AL049437, miR-205-5p, and mitogen-activated protein kinase 1 (MAPK1) was evaluated using luciferase reporter and RNA pull-down assays. RESULTS: The expression of AL049437 was upregulated, while that of miR-205-5p was downregulated in MPTP-induced PDmouse model and MPP+-treated SH-SY5Y cells. Silencing of AL049437 mitigated MPP+-induced neurotoxicity in SH-SY5Y cells, as demonstrated by increased cell viability and reduced cell apoptosis. Furthermore, silencing of AL049437 alleviated MPP+-induced neuroinflammation and oxidative stress, as indicated by the reduction in tumor necrosis factor-α and interleukin-6 levels and reactive oxygen species production. In addition, AL049437 was predominantly localized in the cytoplasm of SH-SY5Y cells and functioned as an miR-205-5p sponge. Moreover, MAPK1 was identified as a downstream target of miR-205-5p. Remarkably, the impact of AL049437 silencing on MPP+-induced neuronal damage could be blocked by miR-205-5p inhibition or MAPK1 overexpression. CONCLUSION: Knockdown of lncRNA AL049437 mitigates MPP+ -induced neuronal injury in SH-SY5Y cells by regulating the miR-205-5p/MAPK1 axis. Our research reveals a novel regulatory mechanism of AL049437 in PD progression.
Authors: Lin Zhao; Li Dong Ding; Zi Hao Xia; Peng Sheng; Meng Meng Shen; Zhong Ming Cai; Bing Chun Yan Journal: Front Pharmacol Date: 2022-03-23 Impact factor: 5.810
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