Qingxin Song1, Yunming Geng2, Yue Li3, Liuli Wang4, Jinyan Qin5. 1. Department of Neurosurgery, Linyi People's Hospital, Linyi, Shandong Province, 276000, China. 2. Department of Neurosurgery, Linyi Fourth People's Hospital, Linyi, Shandong Province, 276000, China. 3. Department of Neurology, Linyi People's Hospital, Linyi, Shandong Province, 276000, China. 4. Department of Health Care, Linyi Lanshan Maternal and Child Health Care Hospital, Linyi, Shandong Province, 276000, China. 5. Department of Neurosurgery, Linyi People's Hospital, Linyi, Shandong Province, 276000, China; Department of Neurology, Linyi People's Hospital, Linyi, Shandong Province, 276000, China; Department of Hyperbaric Oxygen, Linyi People's Hospital, Linyi, Shandong Province, 276000, China. Electronic address: qingjinyan@aol.com.
Abstract
BACKGROUND: Long non-coding RNAs (lncRNAs) have been demonstrated to play important roles in human diseases. Yet, the functions of lncRNAs in neurodegenerative disorders, such as Parkinson's disease (PD) are poorly understood. In this study, we used human neuroblastoma SH-SY5Y cell line as a cell-basedin vitro PD model, and investigated the role of lncRNA, Non-Coding RNA Activated By DNA Damage (NORAD) in 1-methyl-4-phenylpyridinium (MPP+)-induced PD-like cytotoxicity. METHODS: SH-SY5Y cells were culturedin vitro, and treated with MPP + at various concentrations, or of various durations of times to induce PD-like cytotoxic events. qRT-PCR was used to measure MPP+-induced NORAD expression changes. Lentiviral transduction was applied to stably upregulate or downregulate NORAD in SH-SY5Y cells. The effects of NORAD upregulation or downregulation on MPP+-induced cytotoxic events, including dose-dependent and time-dependent cell death, apoptosis, caspase 3/7, reactive Oxygen Species (ROS) and lactate dehydrogenase (LDH) activities, were quantitatively investigated. RESULTS: MPP + induced cytotoxicity, and downregulated NORAD in both dose- and time- dependent manners in SH-SY5Y cells. Lentiviral-induced NORAD upregulation was found to protect against MPP+-induced cytotoxicity in SH-SY5Y cells, as it rescued MPP+-induced cellular destruction and apoptosis, as well as decreased MPP+-induced caspase 3/7, ROS and LDH activities. Alternatively, NORAD downregulation was found to significantly deteriorate MPP+-induced cytotoxicity in SH-SY5Y cells. CONCLUSION: We presented a novel functional role of lncRNA NORAD in regulating human Parkinson's disease.
BACKGROUND: Long non-coding RNAs (lncRNAs) have been demonstrated to play important roles in human diseases. Yet, the functions of lncRNAs in neurodegenerative disorders, such as Parkinson's disease (PD) are poorly understood. In this study, we used humanneuroblastoma SH-SY5Y cell line as a cell-basedin vitro PD model, and investigated the role of lncRNA, Non-Coding RNA Activated By DNA Damage (NORAD) in 1-methyl-4-phenylpyridinium (MPP+)-induced PD-like cytotoxicity. METHODS: SH-SY5Y cells were culturedin vitro, and treated with MPP + at various concentrations, or of various durations of times to induce PD-like cytotoxic events. qRT-PCR was used to measure MPP+-induced NORAD expression changes. Lentiviral transduction was applied to stably upregulate or downregulate NORAD in SH-SY5Y cells. The effects of NORAD upregulation or downregulation on MPP+-induced cytotoxic events, including dose-dependent and time-dependent cell death, apoptosis, caspase 3/7, reactive Oxygen Species (ROS) and lactate dehydrogenase (LDH) activities, were quantitatively investigated. RESULTS: MPP + induced cytotoxicity, and downregulated NORAD in both dose- and time- dependent manners in SH-SY5Y cells. Lentiviral-induced NORAD upregulation was found to protect against MPP+-induced cytotoxicity in SH-SY5Y cells, as it rescued MPP+-induced cellular destruction and apoptosis, as well as decreased MPP+-induced caspase 3/7, ROS and LDH activities. Alternatively, NORAD downregulation was found to significantly deteriorate MPP+-induced cytotoxicity in SH-SY5Y cells. CONCLUSION: We presented a novel functional role of lncRNA NORAD in regulating humanParkinson's disease.
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
Authors: Giulia Gaggi; Andrea Di Credico; Pascal Izzicupo; Giovanni Iannetti; Angela Di Baldassarre; Barbara Ghinassi Journal: Biomedicines Date: 2021-06-29