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Published on: April 24, 2021
Mechanism of miR-143 regulating ERK5 signaling pathway-mediated manganese-induced striatal neuronal apoptosis
Huan Mao1, Yidan Wei2, Cheng Liu2
1Zunyi Medical University School of Public Health, Zunyi, Guizhou 563000, China; Chongqing Yuzhong District Center for Disease Control and Prevention, Chongqing 400010, China.
Abstract:
Overexposure manganese can induce neurotoxicity and apoptosis, in addition, miRNAs are widely involved in the apoptotic process of neurons. Therefore, it is crucial to explore the mechanism of miRNAs in manganese-induced neuronal apoptosis and then to find potential targets. Our present study showed that miR-143 expression was increased in striatum after exposure high doses of manganese. Then, we upregulated miR-143 expression via stereotaxic, and overexpression of miR-143 promoted apoptosis in striatal neurons. Further studies showed a negative regulatory relationship between miR-143 and ERK5, miR-143 upregulation decreased ERK5 mRNA level, inhibiting ERK5 signaling pathway, increasing the expression of Bax and Caspase-3, and exacerbating the apoptosis of striatal neurons. In conclusion, these results suggest that overexpression of miR-143 inhibited the ERK5 signaling pathway and promoted manganese-induced apoptosis in striatal neurons.
Insights
High manganese exposure increases miR-143, a microRNA that promotes neuronal apoptosis by inhibiting the ERK5 pathway. This finding reveals a key mechanism in manganese neurotoxicity.
Area of Science:
- Neuroscience
- Molecular Biology
- Toxicology
Background:
- Manganese overexposure can cause neurotoxicity and neuronal apoptosis.
- MicroRNAs (miRNAs) play a significant role in the apoptotic processes of neurons.
Purpose of the Study:
- To investigate the role of miRNAs in manganese-induced neuronal apoptosis.
- To identify potential miRNA targets involved in this process.
Main Methods:
- Assessed miR-143 expression in the striatum following high-dose manganese exposure.
- Upregulated miR-143 expression stereotaxically in striatal neurons.
- Investigated the regulatory relationship between miR-143 and the ERK5 signaling pathway.
- Measured mRNA levels of ERK5, Bax, and Caspase-3.
Main Results:
- miR-143 expression was elevated in the striatum after manganese exposure.
- Overexpression of miR-143 promoted apoptosis in striatal neurons.
- miR-143 negatively regulated ERK5, decreasing its mRNA levels and inhibiting the ERK5 signaling pathway.
- Inhibition of ERK5 increased Bax and Caspase-3 expression, exacerbating neuronal apoptosis.
Conclusions:
- Overexpression of miR-143 inhibits the ERK5 signaling pathway.
- miR-143 promotes manganese-induced apoptosis in striatal neurons.
- This study elucidates a molecular mechanism underlying manganese neurotoxicity.
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