• HDACi: cellular effects, opportunities for restorative dentistry.

      Duncan, H F; Smith, A J; Fleming, G J P; Cooper, P R; Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland. (2011-12)
      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.
    • Influence of doxorubicin on fluconazole susceptibility and efflux pump gene expression of Candida dubliniensis.

      Schulz, Bettina; Knobloch, Mathias; Moran, Gary P; Weber, Kai; Ruhnke, Markus; Charité-Universitätsmedizin Berlin, Charit Campus Mitte, Medical Department, Division of Oncology and Haematology, Berlin, Germany. bettina_schulz@arcor.de (Medical mycology : official publication of the International Society for Human and Animal Mycology, 2012-05)
      The effect of doxorubicin (DOX) on the fluconazole (FLU) susceptibility of C. dubliniensis was investigated. Isolates were exposed to DOX and FLU in a chequerboard assay and resistance gene expressions were analysed after DOX exposure. The susceptibility of the yeast to FLU was decreased in the presence of DOX in the chequerboard assay with FIC indices suggesting an antagonistic effect. Gene expression analyses showed an overexpression of CdCDR2. Hence, DOX was found to have an impact on resistance mechanisms in C. dubliniensis isolates.