Upregulation of miR‐200a and miR‐204 in MPP<sup>+</sup>‐treated differentiated PC12 cells as a model of Parkinson’s disease

Ardakani, Maryam Talepoor; Delavar, Mohsen Rostamian; Baghi, Masoud; Nasr-Esfahani, Mohammad Hossein; Kiani-Esfahani, Abbas; Ghaedi, Kamran

doi:10.1002/mgg3.548

Cited by 27 publications

(22 citation statements)

References 32 publications

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“…MPP+ is a common dopaminergic neurotoxin that is widely used in in vitro PD models. According to previous report [ 16 ], differentiated PC12 cells were treated with 800 μ M MPP+ for 24 hours. The MTT assay had been preciously used to examine the cell viability of MPP+-treated PC12 cells [ 16 – 18 ].…”

Section: Resultsmentioning

confidence: 99%

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Mir-141-3p Regulates Apoptosis and Mitochondrial Membrane Potential via Targeting Sirtuin1 in a 1-Methyl-4-Phenylpyridinium in vitro Model of Parkinson’s Disease

Zheng

Liu

et al. 2020

BioMed Research International

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Objectives. Parkinson’s disease (PD) is a common neurodegenerative disease characterized by the loss of midbrain dopaminergic neurons in the substantia nigra. The present study investigated miR-141-3p/sirtuin1 (SIRT1) activity in a 1-methyl-4-phenylpyridinium- (MPP+-) induced PC12-cell model of PD. Methods. PC12 cells were exposed to MMP+ following induction of differentiation by nerve growth factor (NGF). miR-141-3p and SIRT1 expressions were examined using RT-qPCR and western blot. Cell viability was evaluated using the MTT assay. Apoptosis percentage, reactive oxygen species (ROS) production, and mitochondrial membrane potential (Δψm) were evaluated using flow cytometry. Expression of Nuclear factor-kappa B- (NF-κB-) related proteins was determined by western blot. Bioinformatic analysis, RT-qPCR, and luciferase reporter assay were used to confirm the interaction between miR-141-3p and SIRT1. Results. miR-141-3p was upregulated, and SIRT1 was downregulated in MPP+-treated PC12 cells. MPP+ treatment also upregulated nitric oxide synthase 1 (Nos1) and α-synuclein. miR-141-3p induced apoptosis, oxidative stress, mitochondrial dysfunction, and downregulated the SIRT1 mRNA expression. The luciferase reporter assay showed that SIRT1 was the target of miR-141-3p. SIRT1 transfection attenuated apoptosis, ROS production and maintained Δψm. SIRT1 also downregulated Nos1, tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), interleukin 6(IL-6) and upregulated B cell lymphoma 2 (Bcl-2) protein. In addition, SIRT1 activator resveratrol blocked the effects of miR-141-3p mimic on Nos1, α-synuclein, and mitochondrial membrane potential. SIRT1 inhibitor sirtinol reversed the biological effects of miR-141-3p. Conclusion. Increased miR-141-3p induced apoptosis, oxidative stress, and mitochondrial dysfunction in MPP+-treated PC12 cells by directly targeting the SIRT1 expression. Our study provided a potential therapeutic strategy for PD.

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Section: Resultsmentioning

confidence: 99%

“…According to previous report [ 16 ], differentiated PC12 cells were treated with 800 μ M MPP+ for 24 hours. The MTT assay had been preciously used to examine the cell viability of MPP+-treated PC12 cells [ 16 – 18 ]. The MTT assay showed that cell viability was decreased after MPP+ treatment ( Figure 2(a) ).…”

Section: Resultsmentioning

confidence: 99%

Mir-141-3p Regulates Apoptosis and Mitochondrial Membrane Potential via Targeting Sirtuin1 in a 1-Methyl-4-Phenylpyridinium in vitro Model of Parkinson’s Disease

Zheng

Liu

et al. 2020

BioMed Research International

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“…The expression of miR-200a was significantly up-regulated in the pheochromocytoma cell line PC12 cells and SH-SY5Y cells following exposure to MPP + that leads to the induction of oxidative stress and cell apoptosis (Salimian et al, 2018;Talepoor Ardakani et al, 2019). Additionally, the transcript level of SIRT1 (a miR-200a target) showed significant down-regulation in the MPP + -treated cells, confirming that SIRT1 may induce DA neuronal apoptosis via P53 and FOXO signaling pathways (Salimian et al, 2018).…”

Section: Mir-200amentioning

confidence: 82%

MicroRNA Dysregulation in Parkinson’s Disease: A Narrative Review

et al. 2021

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Parkinson’s disease (PD) is a severely debilitating neurodegenerative disease, affecting the motor system, leading to resting tremor, cogwheel rigidity, bradykinesia, walking and gait difficulties, and postural instability. The severe loss of dopaminergic neurons in the substantia nigra pars compacta causes striatal dopamine deficiency and the presence of Lewy bodies indicates a pathological hallmark of PD. Although the current treatment of PD aims to preserve dopaminergic neurons or to replace dopamine depletion in the brain, it is notable that complete recovery from the disease is yet to be achieved. Given the complexity and multisystem effects of PD, the underlying mechanisms of PD pathogenesis are yet to be elucidated. The advancement of medical technologies has given some insights in understanding the mechanism and potential treatment of PD with a special interest in the role of microRNAs (miRNAs) to unravel the pathophysiology of PD. In PD patients, it was found that striatal brain tissue and dopaminergic neurons from the substantia nigra demonstrated dysregulated miRNAs expression profiles. Hence, dysregulation of miRNAs may contribute to the pathogenesis of PD through modulation of PD-associated gene and protein expression. This review will discuss recent findings on PD-associated miRNAs dysregulation, from the regulation of PD-associated genes, dopaminergic neuron survival, α-synuclein-induced inflammation and circulating miRNAs. The next section of this review also provides an update on the potential uses of miRNAs as diagnostic biomarkers and therapeutic tools for PD.

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“…Also a study on brain tissue of EAE mice displayed miR-141 overexpression suggesting the potential role of this microRNA in MS [36]. In 2018, two separate studies by our colleagues showed upregulation of miR-141 and miR-200a in MPP+-treated differentiated PC12 cells as a model of Parkinson's disease [37,38]. In our previous study it has been also revealed that both microRNAs expression level and frequency of Th17 cells were higher in MS patients compared to healthy groups [27].…”

Section: Discussionmentioning

confidence: 99%

miR-141 and miR-200a are involved in Th17 cell differentiation by negatively regulating RARB expression

Bahmani

Baghi

Peymani

et al. 2020

Preprint

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Background: Among T helper (Th) lineages differentiated from naïve CD4+ T cells, interleukin (IL)-17-producing Th17 cells are highly correlated with the pathogenesis of autoimmune disorders. Although a series of microRNAs (miRs) that modulate autoimmunity progress have been reported, further studies on microRNAs particularly involved in Th17 lineage commitment are still warranted. Results: In this study, to clarify the involvement of miR-141-3p and miR-200a-3p in Th17 cell differentiation, as well as to explore their potential target gene involved, purified human naïve CD4+ T cells were cultured under Th17 cell polarizing condition. Differentiation process was confirmed applying ELISA method to measure IL-17 secretion and RT-qPCR to assess Th17 cell-defining genes expression during differentiation period. miR-141 and miR-200a expression pattern as well as expression alteration of their predicted downstream genes, which were identified via consensus and integration in-silico approach, was then evaluated by RT-qPCR. Finally direct interaction between both microRNAs and their common predicted target sequence was approved by dual-luciferase reporter assay. Highly increased IL-17 secretion and Th17 lineage-specific genes expression confirmed Th17 cell differentiation. Conclusions: Results demonstrated that miR-141 and miR-200a were Th17 cell-associated microRNAs and their expression levels upregulated significantly during Th17 cell induction. We also found that retinoic acid receptor beta (RARB) gene, whose product has been reported as a negative regulator of Th17 cell generation, was a direct target of both microRNAs and its downregulation could affect the transcriptional level of JAK/STAT pathway genes. Overall, our results introduced two novel Th17 lineage-associated microRNAs and provided a rationale to further clarify the RARB-dependent mechanism of miR-141 and miR-200a to promote Th17 cell differentiation and hence Th17-mediated autoimmunity.

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Upregulation of miR‐200a and miR‐204 in MPP⁺‐treated differentiated PC12 cells as a model of Parkinson’s disease

Cited by 27 publications

References 32 publications

Mir-141-3p Regulates Apoptosis and Mitochondrial Membrane Potential via Targeting Sirtuin1 in a 1-Methyl-4-Phenylpyridinium in vitro Model of Parkinson’s Disease

Mir-141-3p Regulates Apoptosis and Mitochondrial Membrane Potential via Targeting Sirtuin1 in a 1-Methyl-4-Phenylpyridinium in vitro Model of Parkinson’s Disease

MicroRNA Dysregulation in Parkinson’s Disease: A Narrative Review

miR-141 and miR-200a are involved in Th17 cell differentiation by negatively regulating RARB expression

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Upregulation of miR‐200a and miR‐204 in MPP+‐treated differentiated PC12 cells as a model of Parkinson’s disease

Cited by 27 publications

References 32 publications

Mir-141-3p Regulates Apoptosis and Mitochondrial Membrane Potential via Targeting Sirtuin1 in a 1-Methyl-4-Phenylpyridinium in vitro Model of Parkinson’s Disease

Mir-141-3p Regulates Apoptosis and Mitochondrial Membrane Potential via Targeting Sirtuin1 in a 1-Methyl-4-Phenylpyridinium in vitro Model of Parkinson’s Disease

MicroRNA Dysregulation in Parkinson’s Disease: A Narrative Review

miR-141 and miR-200a are involved in Th17 cell differentiation by negatively regulating RARB expression

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Upregulation of miR‐200a and miR‐204 in MPP⁺‐treated differentiated PC12 cells as a model of Parkinson’s disease