Long Noncoding RNA SNHG1 Knockdown Ameliorates Apoptosis, Oxidative Stress and Inflammation in Models of Parkinson’s Disease by Inhibiting the miR-125b-5p/MAPK1 Axis
Xiao Xiao,1 Zhiwen Tan,2 Min Jia,3 Xiaoli Zhou,1 Kemei Wu,3 Yanbing Ding,1 Wenjing Li3 1Department of Encephalopathy, Hubei Provincial Hospital of Traditional Chinese Medicine (Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Hubei Institute of Traditional Chinese Medicine),...
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2021
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| Acceso en línea: | https://doaj.org/article/7c7658606a564a1e881af991a2147d26 |
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| Sumario: | Xiao Xiao,1 Zhiwen Tan,2 Min Jia,3 Xiaoli Zhou,1 Kemei Wu,3 Yanbing Ding,1 Wenjing Li3 1Department of Encephalopathy, Hubei Provincial Hospital of Traditional Chinese Medicine (Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Hubei Institute of Traditional Chinese Medicine), Wuhan City, Hubei Province, People’s Republic of China; 2Department of Encephalopathy, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei Province, People’s Republic of China; 3Department of Neurology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei Province, People’s Republic of ChinaCorrespondence: Wenjing LiDepartment of Neurology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, No. 158 Wuyang Avenue, Enshi, 445000, Hubei Province, People’s Republic of ChinaTel +86 13597789520Fax +86 718 8263395Email 13597789520@163.comBackground: Parkinson’s disease (PD) is a prevalent neurodegenerative disease. Long noncoding RNA small molecule RNA host gene 1 (SNHG1) has been reported to play critical roles in Parkinson’s disease (PD) progression. The study aimed to further elucidate the mechanism of SNHG1 in PD pathogenesis.Methods: The levels of SNHG1, miR-125b-5p and mitogen-activated protein kinase 1 (MAPK1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell viability and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The activity of Caspase-3 or Caspase-9 was measured using a Caspase-3 or Caspase-9 Assay Kit. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, lactic dehydrogenase (LDH) activity, reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were gauged by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was performed to identify the relationship between miR-125b-5p and SNHG1 or MAPK1. The MPTP-induced PD mouse was used as an in vivo model of PD and MPP+-treated SK-N-SH and MN9D cells were used as in vitro models of PD.Results: SNHG1 and MAPK1 were significantly up-regulated while miR-125b-5p was down-regulated in the MPTP-induced PD mouse model and MPP+-induced PD cell models. SNHG1 silence or miR-125b-5p overexpression protected against MPP+-evoked apoptosis, oxidative stress and inflammation in SK-N-SH and MN9D cells. Moreover, SNHG1 acted as a molecular sponge of miR-125b-5p, and the protective impact of SNHG1 silence on MPP+-evoked cell damage was reversed by miR-125b-5p inhibition. Furthermore, MAPK1 was a functional target of miR-125b-5p and its overexpression attenuated the effects of miR-125b-5p restoration in MPP+-triggered cell injury. In addition, the behavioral changes in MPTP-induced PD mouse in vivo model were relieved by SNHG1 silence.Conclusion: SNHG1 knockdown exerted neuroprotective effects in MPP+-evoked cytotoxicity through regulating the miR-125b-5p/MAPK1 axis both in human and mouse PD cell models, highlighting a possible target for PD therapy.Keywords: Parkinson’s disease, SNHG1, miR-125b-5p, MAPK1, cytotoxicity |
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