title: HDACi: cellular effects, opportunities for restorative dentistry.
abstract: Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be 'tipped' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between 'normal' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.
authors.affiliation: Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland.
authors.forename: H F
authors.initials: HF
authors.lastname: Duncan
authors.forename: A J
authors.initials: AJ
authors.lastname: Smith
authors.forename: G J P
authors.initials: GJ
authors.lastname: Fleming
authors.forename: P R
authors.initials: PR
authors.lastname: Cooper
mesh_terms: D000107:Acetylation / Q000187:drug effects*; D000818:Animals; D017209:Apoptosis; D002113:Calcification, Physiologic / Q000187:drug effects; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003782:Dental Pulp / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D003809:Dentin, Secondary / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000145:classification / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D013234:Stem Cells / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors; D016328:NF-kappa B; D017382:Reactive Oxygen Species