Resveratrol induces H3 and H4K16 deacetylation and H2A.X phosphorylation in Toxoplasma gondii

CONTRERAS MS; GANUZA A; CORVI MM; ANGEL SO*

BMC Research Notes

BioMed Central Ltd.

Año: 2021 p. 1 - 8

1756-0500

Objective: Resveratrol(RSV) is a multitargetdrug that has demonstrated activity against Toxoplasmagondii in macrophage and human foreskin fibroblast (HFF) cell lineinfection models. However, the mechanism of action of RSV has not yet been determined.Thus, with the aim of identifying a possible mechanism of the anti-T. gondii activity of this compound, weanalyzed the effects of RSV on histones H3 and H4 lysine 16 acetylation(H4K16). We also analyzed RSV-induced DNA damage to intracellular tachyzoitesby using the DNA damage marker phosphorylated histone H2A.X (gH2AX).Results:RSV inhibited intracellular T. gondiitachyzoite growth at concentrations below the toxic threshold for host cells.The IC50 value after 24 h of treatment was 53 mM.RSV induced a reduction in H4K16 acetylation (H4K16ac), a marker associated with transcription,DNA replication and homologous recombination repair. A similar deacetylationeffect was observed on histone H3. RSV also increased T. gondii H2A.X phosphorylation at the SQE motif (termed γH2A.X), whichis a DNA damage-associatedposttranslationalmodification. Our findings suggest a possible link between RSV and DNA damageor repair processes that is possibly associated with DNA replicationstress.