Mode of Action: Inhibition of Histone Deacetylase, Altering WNT-Dependent Gene Expression, and Regulation of Beta-Catenin—Developmental Effects of Valproic Acid
| العنوان: | Mode of Action: Inhibition of Histone Deacetylase, Altering WNT-Dependent Gene Expression, and Regulation of Beta-Catenin—Developmental Effects of Valproic Acid |
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| المؤلفون: | Jeanette A Wiltse |
| المصدر: | Critical Reviews in Toxicology. 35:727-738 |
| بيانات النشر: | Informa UK Limited, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | medicine.medical_specialty, Beta-catenin, medicine.drug_class, Gene Expression, Biology, Toxicology, Species Specificity, Pregnancy, Internal medicine, medicine, Animals, Humans, Enzyme Inhibitors, beta Catenin, Valproic Acid, Histone deacetylase inhibitor, Neural tube, Wnt signaling pathway, Cell biology, Histone Deacetylase Inhibitors, Wnt Proteins, Teratogens, medicine.anatomical_structure, Endocrinology, Trichostatin A, Catenin, biology.protein, Anticonvulsants, Female, lipids (amino acids, peptides, and proteins), Histone deacetylase, Signal transduction, Signal Transduction, medicine.drug |
| الوصف: | Valproic acid (VPA) has long been known to cause spina bifida, a neural tube defect, and other effects in fetuses of women treated with this drug. Toxicological tests in laboratory mice and rats at human therapeutic doses also show neural tube and other defects. Studies show that VPA alters Wnt signaling in human and animal cells, inducing Wnt-dependent gene expression at doses that cause developmental effects. Structural analogues of VPA that do not have this effect on Wnt signaling do not cause developmental effects. Similarly, Trichostatin A, a compound that mimics VPA in its effects on Wnt gene expression, also causes similar developmental effects. Alteration of Wnt signaling is empirically well supported as the postulated mode of action (MOA) for VPA's developmental effects in animals. VPA causes alteration of Wnt signaling in both human and animal cells systems at the same dose levels. The correspondence of effects on signaling and of effects on development in animals and humans supports the view that alteration of Wnt signaling is a relevant MOA in humans. |
| تدمد: | 1547-6898 1040-8444 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e8cebe29de7e4f8fe5c8b274659c33d https://doi.org/10.1080/10408440591007403 |
| رقم الأكسشن: | edsair.doi.dedup.....1e8cebe29de7e4f8fe5c8b274659c33d |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 15476898 10408444 |
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