Manganese exposure results in decrease in YTHDF2 protein expression and YTHDF2 transcripts in neurons

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2020-01-01
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Huffman, Elliana
Malovic, Emir
Kanthasamy, Anumantha
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Anumantha Kanthasamy
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Biomedical Sciences

The Department of Biomedical Sciences aims to provide knowledge of anatomy and physiology in order to understand the mechanisms and treatment of animal diseases. Additionally, it seeks to teach the understanding of drug-action for rational drug-therapy, as well as toxicology, pharmacodynamics, and clinical drug administration.

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The Department of Biomedical Sciences was formed in 1999 as a merger of the Department of Veterinary Anatomy and the Department of Veterinary Physiology and Pharmacology.

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1999–present

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  • College of Veterinary Medicine (parent college)
  • Department of Veterinary Anatomy (predecessor, 1997)
  • Department of Veterinary Physiology and Pharmacology (predecessor, 1997)

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One of the most well characterized RNA modifications is the addition of a methyl group to the amine nitrogen of adenosine nucleotides. This methylation, named N6-methyladenoside (m6A), is known to affect the stability of mRNA. YTHDF2 is a reader protein responsible for recognition and degradation of transcripts containing m6A methylation. Previous work in our lab has shown that levels of YTHDF2 are decreased in astrocytes following exposure to manganese. Manganese exposure causes oxidative stress in the cell and is known to cause a disease called manganism, which has many similarities to Parkinson’s disease. The neurotoxicity of manganese may also be affecting the levels of YTHDF2 and related proteins in neurons. The purpose of this project was to see if manganese exposure also affects YTHDF2 levels in neurons, and further determine the role of YTHDF2 in response to a stimulus like manganese. Mn9D neuronal cells were subjected to 24 hour treatments with 300μM of manganese. Western blot analysis revealed a decrease in YTHDF2 protein expression compared to a control. qRT-PCR also showed a decrease in the mRNA of YTHDF2 as well as two other m6A associated proteins METTL3 and FTO. Taken together with results from previous studies, this project demonstrates that manganese exposure causes a decrease in YTHDF2 indicating it may be involved in the cellular response to neurotoxicity, and oxidative stress and may be impacted by prosurvival pathways.

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Wed Jan 01 00:00:00 UTC 2020