The molecular mechanism of miRNA-195-5p regulating ERK involvement in abnormal phosphorylation of Tau protein by aluminum maltol in PC12 cells Article Swipe
Dan Gao
,
Jinzhu Yin
,
Yunwei Zhang
,
Dan Zhao
,
Xiao Han
,
Jiaping Huan
,
Tianshu Wang
,
Shimeng Xu
,
Linping Wang
,
Jing Song
,
Huifang Zhang
,
Q. L. Niu
,
Xiaoting Lu
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3699394/v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3699394/v1
Although aluminum is ubiquitously present on Earth, it is not necessary for life. Aluminum is a metal element that can induce neurotoxicity. The neurotoxicity of aluminum is mainly caused by the aggregation of abnormally phosphorylated tau protein to form neurofibrillary tangles (NFT). The phosphorylation of tau is regulated by both kinases and phosphatases. ERK is involved in PHF-type tau hyperphosphorylation. Recent studies have revealed that the interaction between microRNAs (miRNAs) and the ERK/MAPK cascade is related to maintaining the normal function of the nervous system. miR-195 is involved in the early development of AD with a potential impact on cognition. Therefore, we speculate that miRNA-195 may regulate ERK activity, thereby causing hyperphosphorylation of tau protein and neurotoxicity. Objective : To explore the role of miRNA-195-5p in regulating ERK in the process of Al (mal) 3 -induced tau hyperphosphorylation. Methods : PC12 cells were exposed to Al(mal) 3 . The ERK activation inhibitor U0126 and miRNA-195-5p plasmid were selected for intervention. The exposure groups included the control group, 100 µmol/L Al(mal) 3 group, 200 µmol/L Al(mal) 3 group, and 400 µmol/L Al(mal) 3 group. The intervention groups of U0126 included the control group, 200 µmol/L Al(mal)3 group, DMSO group, 50 µmol/L U0126 group, and 50 µmol/L U0126 + 200 µmol/L Al(mal) 3 group. The intervention groups of miRNA-195-5p included the control group, 200 µmol/L Al(mal)3 exposure group, blank plasmid group, and miRNA-195-5p overexpression + 200 µmol/L Al(mal) 3 group. Cell viability was detected by CCK8 assay. The distribution of aluminum and the expression of tau protein in PC12 cells were observed by immunofluorescence. ERK, P-ERK, tau5, PHF and NFT were detected by Western blotting. mRNA-ERK and miRNA-195-5p were detected by RT‒PCR. Results : The fluorescence signal showed that aluminum is mainly distributed in the cytoplasm. As the concentration of Al(mal) 3 increases, the fluorescence signal gradually increases. With the increase in Al(mal) 3 concentration, PC12 cell viability decreased, the expression of miRNA-195-5p decreased, and the expression of P-ERK, tau5, PHF and NFT increased. After U0126 intervention, the expression levels of tau5, PHF, and NFT protein in the U0126 + 200 µmol/L Al(mal) 3 group decreased compared to those in the 200 µmol/L Al(mal) 3 group. There is an interaction effect between U0126 and Al(mal) 3 on the expression of tau5, PHF, and NFT proteins. After transfection with microRNA-195-5P, the expression levels of tau5, PHF, and NFT protein in the miRNA-195-5p overexpression + 200 µmol/L Al(mal) 3 group decreased compared to those in the the 200 µmol/L Al(mal) 3 group. There is an interaction effect between miRNA-195-5p and Al(mal) 3 on the expression of tau5, PHF, and NFT proteins. Conclusion: miRNA-195-5p regulates ERK involvement in the abnormal phosphorylation of Tau protein by aluminum maltol in PC12 cells.
Related Topics
Concepts
Hyperphosphorylation
Neurotoxicity
MAPK/ERK pathway
Kinase
Phosphorylation
Tau protein
Chemistry
microRNA
p38 mitogen-activated protein kinases
Phosphatase
Protein kinase A
Molecular biology
Toxicity
Biology
Internal medicine
Biochemistry
Medicine
Gene
Alzheimer's disease
Disease
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-3699394/v1
- https://www.researchsquare.com/article/rs-3699394/latest.pdf
- OA Status
- green
- Cited By
- 1
- References
- 29
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4389729252
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4389729252Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.3.rs-3699394/v1Digital Object Identifier
- Title
-
The molecular mechanism of miRNA-195-5p regulating ERK involvement in abnormal phosphorylation of Tau protein by aluminum maltol in PC12 cellsWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-12-14Full publication date if available
- Authors
-
Dan Gao, Jinzhu Yin, Yunwei Zhang, Dan Zhao, Xiao Han, Jiaping Huan, Tianshu Wang, Shimeng Xu, Linping Wang, Jing Song, Huifang Zhang, Q. L. Niu, Xiaoting LuList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-3699394/v1Publisher landing page
- PDF URL
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https://www.researchsquare.com/article/rs-3699394/latest.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-3699394/latest.pdfDirect OA link when available
- Concepts
-
Hyperphosphorylation, Neurotoxicity, MAPK/ERK pathway, Kinase, Phosphorylation, Tau protein, Chemistry, microRNA, p38 mitogen-activated protein kinases, Phosphatase, Protein kinase A, Molecular biology, Toxicity, Biology, Internal medicine, Biochemistry, Medicine, Gene, Alzheimer's disease, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1Per-year citation counts (last 5 years)
- References (count)
-
29Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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