Results of recent studies involving valproic acid, used for decades as an anti-convulsant drug, show that it can interact with the conformation of DNA and regulate gene expression.
These are some of the key findings from a project led by biologist Maria Luiza S. Mello at the University of Campinas (UNICAMP) in the state São Paulo, Brazil, with the collaboration of Benedicto de Campos Vidal, Emeritus Professor in the Biology Institute's Department of Structural and Functional Biology.
The group has been studying the functions of valproic acid, or sodium valproate (VPA), for over a decade and have demonstrated the compound's action on the expression of genes associated with diabetes in cellular models (read more at: agencia.fapesp.br/23819).
Its interaction with DNA is reported in an article published in the International Journal of Biological Macromolecules. The study was part of a Thematic Project supported by FAPESP to study the action of VPA.
Elucidating the drug's action mechanisms is important because it paves the way for novel pharmaceutical research." Maria Luiza S. Mello, Biologist, University of Campinas
Changes in histones and DNA
The epigenetic action of VPA – its capacity to influence gene expression without changing the subject's DNA – was already well-known. "In 2017, Iranian researchers mooted the possibility of an action mechanism that was not only epigenetic but also involved direct interaction with the structure of histone H1," Mello said.
"So we decided to study how histones and DNA itself respond to VPA." Histones are cell nucleus proteins and key components of chromatin, the substance of chromosomes. These are made up of DNA tightly wound around histones.
The group tested samples containing VPA-DNA and VPA-histone mixtures. They analyzed the interactions between H1, H3, and VPA by means of high-performance polarization microscopy and Fourier-transform infrared microspectroscopy, using equipment previously acquired by FAPESP for Campos Vidal.
"The samples with DNA, histones, and VPA were analyzed first under the polarization microscope and then under the infrared microspectroscope" Mello said. This type of measurement, performed with a spectroscope coupled to a special microscope, produces a spectral signature of molecular structure – a graphical record of how the molecules are…