Protective effects of microRNA-330 on amyloid β-protein production, oxidative stress, and mitochondrial dysfunction in Alzheimer's disease by targeting VAV1 via the MAPK signaling pathway
| Autor: | Yi Tian, Ying Zhou, Zhao-Yun Liu, Zhou-Fan Wang, Hui Hong, Juan Chen, Wei Li |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
VAV1 Amyloid MAP Kinase Signaling System Cell medicine.disease_cause Protective Agents Biochemistry Superoxide dismutase 03 medical and health sciences Mice 0302 clinical medicine Alzheimer Disease microRNA medicine Animals Proto-Oncogene Proteins c-vav Molecular Biology Neurons Reporter gene Amyloid beta-Peptides biology Chemistry Cell Biology Molecular biology Mitochondria Blot Mice Inbred C57BL Disease Models Animal MicroRNAs Oxidative Stress 030104 developmental biology medicine.anatomical_structure biology.protein 030217 neurology & neurosurgery Oxidative stress Signal Transduction |
| Zdroj: | Journal of cellular biochemistry. 119(7) |
| ISSN: | 1097-4644 |
| Popis: | This study aims to explore the effect of miR-330 targeting VAV1 on amyloid β-protein (Aβ) production, oxidative stress (OS), and mitochondrial dysfunction in Alzheimer's disease (AD) mice through the MAPK signaling pathway. Putative targeted gene of miR-330 was performed by a miRNA target prediction website and dual-luciferase reporter gene assay. AD mouse model was successfully established. Fourteen C57 mice were randomized into AD and control groups. The positive protein expression rate of VAV1 was measured by immunohistochemistry. Neuron cells were assigned into control, blank, negative control (NC), miR-330 mimics, miR-330 inhibitors, siRNA-VAV1, and miR-330 inhibitors + siRNA-VAV1 groups. Expression of miR-330, VAV1, ERK1, JNK1, P38MAPK, Aβ, COX, and lipoprotein receptor-related protein-1 (LRP-1) were determined using RT-qPCR and Western blotting. Colorimetry was applied to measure the levels of OS parameters of superoxide dismutase (SOD) and malondialdehyde (MDA). Aβ production in brain tissue was detected using ELISA, while that in neuron cell was measured by radioimmunoassay. MiR-330 was down-regulated in neuron cells of AD mice and VAV1 was negatively regulated by miR-330. Compared with the control group, the positive protein expression rate of VAV1 was significantly elevated in the AD group. Overexpression of miR-330 decreased the expression of VAV1, ERK1, JNK1, P38MAPK, and Aβ, but increased the expression of COX and LRP-1. AD mice revealed elevated Aβ production and MDA with decreased SOD level. The result indicates that overexpressed miR-330 targeting VAV1 through the MAPK signaling pathway reduces Aβ production and alleviates OS and mitochondrial dysfunction in AD. |
| Databáze: | OpenAIRE |
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