Histone acetyltransferase and Polo-like kinase 3 inhibitors prevent rat galactose-induced cataract
| Autor: | Mayumi Inami, Yoshihiro Takamura, Seiji Miyake, Masaru Inatani, Kazuma Kamata, Masaya Oki, Fumito Kanada |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
genetic structures Microarray lcsh:Medicine Cell Cycle Proteins Polo-like kinase Protein Serine-Threonine Kinases Pharmacology Article Cataract Diabetes Mellitus Experimental PLK3 Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Cataracts Lens Crystalline medicine Animals Enzyme Inhibitors lcsh:Science Histone Acetyltransferases Multidisciplinary biology business.industry lcsh:R Galactose Histone acetyltransferase medicine.disease eye diseases Rats 030104 developmental biology 030221 ophthalmology & optometry biology.protein Epigenetics lcsh:Q sense organs Histone deacetylase business Transcription Ex vivo |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Diabetic cataracts can occur at an early age, causing visual impairment or blindness. The detailed molecular mechanisms of diabetic cataract formation remain incompletely understood, and there is no well-documented prophylactic agent. Galactose-fed rats and ex vivo treatment of lenses with galactose are used as models of diabetic cataract. To assess the role of histone acetyltransferases, we conducted cataract prevention screening with known histone acetyltransferase (HAT) inhibitors. Ex vivo treatment with a HAT inhibitor strongly inhibited the formation of lens turbidity in high-galactose conditions, while addition of a histone deacetylase (HDAC) inhibitor aggravated turbidity. We conducted a microarray to identify genes differentially regulated by HATs and HDACs, leading to discovery of a novel cataract causative factor, Plk3. Plk3 mRNA levels correlated with the degree of turbidity, and Plk3 inhibition alleviated galactose-induced cataract formation. These findings indicate that epigenetically controlled Plk3 influences cataract formation. Our results demonstrate a novel approach for prevention of diabetic cataract using HAT and Plk3 inhibitors. |
| Databáze: | OpenAIRE |
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