Sodium valproate (VPA) interactions with DNA and histones

Autor(es)

Vidal, Benedicto de Campos ^[1] ; Mello, Maria Luiza S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas Unicamp, Inst Biol, Dept Struct & Funct Biol, BR-13083862 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Macromolecules; v. 163, p. 219-231, NOV 15 2020.
• Citações Web of Science: 0

Resumo

Valproic acid/sodium valproate (VPA) constitutes a widely prescribed drug for the treatment of seizure disorders and is a well-known epigenetic agent, inducing the acetylation of histones and affecting the methylation status of DNA and histones, with consequences on gene expression. Because this drug has been recently reported to exert affinity for histone H1, and to a minor degree for DNA, in this work, we investigated a possible interaction of sodium valproate with DNA and histones H1 and H3 using high-performance polarization microscopy and Fourier-transform infrared (FTIR) microspectroscopy. The preparations under examination consisted of hemispheres resulting from drop-casting samples containing VPA-DNA and VPA-histone mixtures. The results indicated that VPA may interact with DNA and histones, inducing changes in the textural superstructure and molecular order of the DNA possibly through van der Waals forces, and in histone H1 and H3 conformations, probably as a result of electrostatic binding between the drug and protein amino acid residues. These results contribute to a better understanding of the pharmacological potential of VPA. The precise sites and mechanisms involved in these interactions would certainly benefit from investigations provided by complementary methodologies. (C) 2020 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 15/10356-2 - Atuação do ácido valproico ao nível estrutural e funcional da cromatina
• Beneficiário: Maria Luiza Silveira Mello
• Modalidade de apoio: Auxílio à Pesquisa - Temático