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Inhibition of miR-128 Abates A?-Mediated Cytotoxicity by Targeting PPAR-? via NF-?B Inactivation in Primary Mouse Cortical Neurons and Neuro2a Cells.

ABSTRACT: PURPOSE:Alzheimer's disease (AD) is the sixth most common cause of death in the United States. MicroRNAs have been identified as vital players in neurodegenerative diseases, including AD. microRNA-128 (miR-128) has been shown to be dysregulated in AD. This study aimed to explore the roles and molecular mechanisms of miR-128 in AD progression. MATERIALS AND METHODS:Expression patterns of miR-128 and peroxisome proliferator-activated receptor gamma (PPAR-?) messenger RNA in clinical samples and cells were measured using RT-qPCR assay. PPAR-? protein levels were determined by Western blot assay. Cell viability was determined by MTT assay. Cell apoptotic rate was detected by flow cytometry via double-staining of Annexin V-FITC/PI. Caspase 3 and NF-?B activity was determined by a Caspase 3 Activity Assay Kit or NF-?B p65 Transcription Factor Assay Kit, respectively. Bioinformatics prediction and luciferase reporter assay were used to investigate interactions between miR-128 and PPAR-? 3'UTR. RESULTS:MiR-128 expression was upregulated and PPAR-? expression was downregulated in plasma from AD patients and amyloid-? (A?)-treated primary mouse cortical neurons (MCN) and Neuro2a (N2a) cells. Inhibition of miR-128 decreased A?-mediated cytotoxicity through inactivation of NF-?B in MCN and N2a cells. Moreover, PPAR-? was a target of miR-128. PPAR-? upregulation attenuated A?-mediated cytotoxicity by inactivating NF-?B in MCN and N2a cells. Furthermore, PPAR-? downregulation was able to abolish the effect of anti-miR-128 on cytotoxicity and NF-?B activity in MCN and N2a cells. CONCLUSION:MiR-128 inhibitor decreased A?-mediated cytotoxicity by upregulating PPAR-? via inactivation of NF-?B in MCN and N2a cells, providing a new potential target in AD treatment.

SUBMITTER: Geng L

PROVIDER: S-EPMC6192880 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Inhibition of miR-128 Abates Aβ-Mediated Cytotoxicity by Targeting PPAR-γ via NF-κB Inactivation in Primary Mouse Cortical Neurons and Neuro2a Cells.

Geng Lijiao L Zhang Tao T Liu Wei W Chen Yong Y

Yonsei medical journal 20181101 9

<h4>Purpose</h4>Alzheimer's disease (AD) is the sixth most common cause of death in the United States. MicroRNAs have been identified as vital players in neurodegenerative diseases, including AD. microRNA-128 (miR-128) has been shown to be dysregulated in AD. This study aimed to explore the roles and molecular mechanisms of miR-128 in AD progression.<h4>Materials and methods</h4>Expression patterns of miR-128 and peroxisome proliferator-activated receptor gamma (PPAR-γ) messenger RNA in clinical ...[more]

PMID: 30328325

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Project description:IntroductionSudarshankriya pranayama is the control of breathing movements to regulate the energy flow throughout the body, which has shown to positively affect immune function, autonomic nervous system and psychologic-neuro pathways. The practice of pranayama has been proven to show several benefits such as reduction in stress levels, relieves anxiety and depression, increase in antioxidant levels, reduces insulin resistance and improves respiratory function.AimThe objective of the study was to evaluate the levels of Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ), Nuclear Factor-Kappa B (NF-κB) and the presence of Red Complex Microorganisms (RCM) such as Treponema denticola, Porphyromonas gingivalis and Tannerella forsythia in the subgingivalpl aque samples of chronic periodontitis subjects before and after intervention with pranayama as an adjunct to Scaling and Root Planing (SRP).Materials and methodsA total of 30 subjects (control group) were treated with SRP and 30 subjects (pranayama group) underwent SRP and pranayama for three months. Probing Pocket Depth (PPD), Clinical Attachment Level (CAL), Bleeding Index (BI) and Plaque Index (PI) were recorded and the presence of PPAR-γ, NF-κB and RCM were assessed at baseline and after three months using polymerase chain reaction. ANCOVA test was done to compare the clinical parameters between the groups. Fisher's Exact test was done to identify RCM and Mann-Whitney and Wilcoxon-signed test was used to identify the expression of NF-κB and PPAR-γ in the plaque samples.ResultsThe change in the mean CAL from baseline to third month was significantly higher in pranayama group compared to control group (p≤0.05). There was a statistically significant reduction in the expression of NF-κB and increase in PPAR-γ expression levels in pranayama group on comparison with the control group (p<0.001). The reduction in number of positive samples with T.denticola, P.gingivalis and T.forsythia at third month post-intervention did not affect the change in the expression levels of NF-κB and PPAR-γ.ConclusionThe CAL showed significant improvement with reduction in the RCM, NF-κB and increase in PPAR-γ levels in subjects who underwent pranayama as an adjunct to SRP. In future, pranayama can be used as an additional treatment modality to provide a new dimension in treatment of periodontitis.

Project description:Progressive liver fibrosis, caused by chronic viral infection and metabolic disorders, results in the development of cirrhosis and hepatocellular carcinoma. However, no antifibrotic therapies have been approved to date. In our previous study, adeno‑associated virus (AAV) short hairpin RNAs (shRNAs) targeting hepatitis B virus (HBV) and transforming growth factor (TGF)‑β administration could persistently inhibit HBV replication and concomitantly prevent liver fibrosis. However, the differentially expressed proteins and critical regulatory networks of AAV‑shRNA treatment remain unclear. Accordingly, in the present study, we aimed to analyze differentially expressed proteins in the liver of AAV‑shRNA‑treated mice with HBV infection and liver fibrosis using isobaric tags for relative and absolute quantitation (iTRAQ)‑based quantitative proteomics and to elucidate the underlying antifibrotic mechanisms. In total 2,743 proteins were recognized by iTRAQ‑based quantitative proteomics analysis. Gene Ontology analysis revealed that the differentially expressed proteins mostly participated in peptide metabolism in the biological process category, cytosolic ribosomes in the cell component category, and structural constituents of ribosomes in the molecular function category. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that oxidative stress and the peroxisome proliferator‑activated receptor (PPAR) signaling pathway were activated after treatment. Verification studies revealed that AAV‑shRNAs inhibited hepatic stellate cell activation and inflammation by suppressing nuclear factor‑κB p65 phosphorylation and α‑smooth muscle actin expression via upregulation of PPAR‑γ. Hepatocytes steatosis was also decreased by activating the PPAR signaling pathway and improving lipid metabolism. The expression level of TGF‑β was decreased due to upregulation of PPAR‑γ expression and direct inhibition using AAV‑shRNA targeting TGF‑β. TGF‑β‑induced oxidative stress was suppressed by increasing glutathione S‑transferase Pi 1 and reducing peroxiredoxin 1. Collectively, the present results indicated that AAV‑shRNAs were effective in modulating liver fibrosis by reducing oxidative stress, inflammation and activating the PPAR signaling pathway.

Dataset Information

Inhibition of miR-128 Abates A?-Mediated Cytotoxicity by Targeting PPAR-? via NF-?B Inactivation in Primary Mouse Cortical Neurons and Neuro2a Cells.

Publications

Inhibition of miR-128 Abates Aβ-Mediated Cytotoxicity by Targeting PPAR-γ via NF-κB Inactivation in Primary Mouse Cortical Neurons and Neuro2a Cells.

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