The Aneugenicity of Ketone Bodies in Colon Epithelial Cells Is Mediated by Microtubule Hyperacetylation and Is Blocked by Resveratrol
| Autor: | Akira Kubo, Haruka Sudo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
Colon Ketone Bodies Resveratrol medicine.disease_cause Microtubules Catalysis Antioxidants Article Inorganic Chemistry chemistry.chemical_compound Microtubule medicine Animals Humans aneuploidy Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy Cells Cultured microtubule severing Microtubule severing Tubulin deacetylation biology diabetes Chemistry Organic Chemistry Acetylation Epithelial Cells General Medicine Fibroblasts HDAC3 Aneugens Computer Science Applications Cell biology Rats Tubulin colon cancer Colonic Neoplasms biology.protein Ketone bodies Carcinogenesis |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 17 International Journal of Molecular Sciences, Vol 22, Iss 9397, p 9397 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22179397 |
| Popis: | Diabetes mellitus (DM) is considered to be associated with an increased risk of colorectal cancer. Recent studies have also revealed that tubulin hyperacetylation is caused by a diabetic status and we have reported previously that, under microtubule hyperacetylation, a microtubule severing protein, katanin-like (KL) 1, is upregulated and contributes to tumorigenesis. To further explore this phenomenon, we tested the effects of the ketone bodies, acetoacetate and β-hydroxybutyrate, in colon and fibroblast cells. Both induced microtubule hyperacetylation that responded differently to a histone deacetylase 3 knockdown. These two ketone bodies also generated intracellular reactive oxygen species (ROS) and hyperacetylation was commonly inhibited by ROS inhibitors. In a human fibroblast-based microtubule sensitivity test, only the KL1 human katanin family member showed activation by both ketone bodies. In primary cultured colon epithelial cells, these ketone bodies reduced the tau protein level and induced KL1- and α-tubulin acetyltransferase 1 (ATAT1)-dependent micronucleation. Resveratrol, known for its tumor preventive and tubulin deacetylation effects, inhibited this micronucleation. Our current data thus suggest that the microtubule hyperacetylation induced by ketone bodies may be a causal factor linking DM to colorectal carcinogenesis and may also represent an adverse effect of them that needs to be controlled if they are used as therapeutics. |
| Databáze: | OpenAIRE |
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