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TRPV4 contributes to ER stress: Relation to apoptosis in the MPP+-induced cell model of Parkinson's disease

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机构： [a]Faculty of Life science and Technology, Kunming University of Science and Technology, Kunming 650500, China [b]Department of Anesthesiology, The First People's Hospital of Yunnan Province, Kunming 650032, China [c]Medical School, Kunming University of Science and Technology, Kunming 650500, China

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关键词： ER stress MPP+ Parkinson's disease TRPV4

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Aims: Parkinson's disease (PD) is a multifactorial neurodegenerative disorder. Its molecular mechanism is still unclear. Endoplasmic reticulum (ER) stress has been highlighted in PD. Transient receptor potential vanilloid 4 (TRPV4) is a kind of nonselective calcium cation channel. A defined role for TRPV4 in PD has not been reported. The purpose of the present research was to investigate the molecular mechanisms by which TRPV4 regulates ER stress induced by the 1-methyl-4-phenylpyridinium ion (MPP+) in PC12 cells. Main methods: PC12 cells were pretreated with the TRPV4-specific antagonist HC067047 or transfected with TRPV4 siRNA followed by treatment with MPP+. Cell viability was measured by the CCK-8 Assay. The expression of TRPV4, sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94), C/EBP homologous protein (CHOP), procaspase-12, and tyrosine hydroxylase (TH) was detected by western blot and RT-PCR. Key findings: The expression of TRPV4 was upregulated, while cell viability was decreased by MPP+, which was reversed by HC067047. The ER stress common molecular signature SERCA2 was depressed by MPP+. Moreover, MPP+ induced upregulation of GRP78, GRP94, CHOP, and decrease in procaspase-12 and TH. HC067047 and TRPV4 siRNA reversed MPP+-induced ER stress and restored TH production. Significance: TRPV4 functions upstream of ER stress induced by MPP+ and holds promise as a prospective pharmacotherapy target for PD. © 2020

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出版当年[2020]版：

大类 | 3 区医学

小类 | 3 区医学：研究与实验 3 区药学

最新[2023]版：

大类 | 2 区

医学

小类 | 2 区医学：研究与实验 2 区药学

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出版当年[2019]版：

Q2 MEDICINE, RESEARCH & EXPERIMENTAL Q2 PHARMACOLOGY & PHARMACY

最新[2023]版：

Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 PHARMACOLOGY & PHARMACY

影响因子： 5.2 最新[2023版] 5.3 最新五年平均 3.647 出版当年[2019版] 3.413 出版当年五年平均 3.448 出版前一年[2018版] 5.037 出版后一年[2020版]

第一作者：

第一作者机构： [a]Faculty of Life science and Technology, Kunming University of Science and Technology, Kunming 650500, China [b]Department of Anesthesiology, The First People's Hospital of Yunnan Province, Kunming 650032, China

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