The Human Histone Deacetylase Family
Since the identification of the first histone deacetylase (Taunton et al., Science 272, 408–411), several new members have been isolated. They can loosely be separated into entities on the basis of their similarity to various yeast histone deacetylases. The first class is represented by its closeness to the yeast Rpd3-like proteins, and the second most recently discovered class has similarities to yeast Hda1-like proteins. However, due to the fact that several different research groups isolated the Hda1-like histone deacetylases independently, there have been various different nomenclatures used to describe the various members, which can lead to confusion in the interpretation of this family’s functions and interactions. With the discovery of another novel murine histone deacetylase, homologous to yeast Sir2, the number of members of this family is set to increase, as 7 human homologues of this gene have been isolated. In the light of these recent discoveries, we have examined the literature data and conducted a database analysis of the isolated histone deacetylases and potential candidates. The results obtained suggest that the number of histone deacetylases within the human genome may be as high as 17 and are discussed in relation to their homology to the yeast histone deacetylases.[1]
Histone Deacetylase Inhibitors: Overview and Perspectives
Histone deacetylase inhibitors (HDACi) comprise structurally diverse compounds that are a group of targeted anticancer agents. The first of these new HDACi, vorinostat (suberoylanilide hydroxamic acid), has received Food and Drug Administration approval for treating patients with cutaneous T-cell lymphoma. This review focuses on the activities of the 11 zinc-containing HDACs, their histone and nonhistone protein substrates, and the different pathways by which HDACi induce transformed cell death. A hypothesis is presented to explain the relative resistance of normal cells to HDACi-induced cell death.[2]
Prospects: Histone deacetylase inhibitors
Histone deacetylase (HDAC), inhibitors represent a new class of targeted anti-cancer agents. Several of these compounds are in clinical trials with significant activity against a spectrum of both hematologic and solid tumors at doses that are well tolerated by the patients. The HDAC inhibitors are a structurally diverse group of molecules that can induce growth arrest, differentiation, apoptosis, and autophagocytic cell death of cancer cells. While the base sequence of DNA provides the genetic code for proteins, the expression of genes is regulated, in large part, by the structure of the chromatin proteins around which the DNA is wrapped (epigenetic gene regulation). The acetylation and deacetylation of the lysines in the tails of the core histones, among the most extensively studied aspects of chromatin structure, is controlled by the action of two families of enzymes, histone deacetylases (HDACs) and histone acetyltransferases (HATs). Protein components of transcription factor complexes and many other non-histone proteins are also substrates for HDACs and HATs. The structure and activity of these non-histone proteins may be altered by acetylation/deacetylation with consequent effects on various cell functions including gene expression, cell cycle progression, and cell death pathways. This review focuses on several key questions with respect to the mechanism of action of HDACi, including, what are the different cell phenotypes induced by HDACi, why are normal cells compared to transformed cells relatively resistant to HDACi induced cell death, why are certain tumors more responsive to HDACi than others, and what is the basis of the selectivity of HDACi in altering gene expression.[3]
Synthesis and Characterization of Epichlorohydrin- Crosslinked Lumbang (Aleurites moluccana)-Derived Activated Carbon Chitosan Composite as Cr(VI) Bioadsorbent
Lumbang (Aleurites moluccana) activated carbon chitosan composite crosslinked with epichlorohydrin was synthesized for batch adsorption of toxic Cr(VI) ion from an aqueous solution. The synthesized biosorbent was characterized by instrumental techniques such as FTIR and SEM. The surface morphology of the adsorbent had a porous texture with round- and elliptical-shaped voids as adsorption sites for the adsorbate. Some functionalities including –OH and –NH2 groups were identified on the surfaces. The synthesized activated lumbang-biocharcoal chitosan composite crosslinked with epichlorohydrin adsorbent at the optimized conditions adsorbed 93% of Cr(VI) ion. The investigated adsorption phenomenon described a chemisorption process due to the functional groups identified and the high porosity of the adsorbent surfaces. [4]
Derivatives of Ferulic Acid: Structure, Preparation and Biological Activities
Ferulic acid is a natural compound that possesses multiple physiological and pharmaceutical functions. The chemical, physical, and pharmaceutical properties of this phenolic acid can be improved by derivatives with other active compounds. This sentence (Hence, such improvements can widen the applications of ferulic acid in the food, cosmetic, and pharmaceutical industries.) has been deleted. This article reviewed the identification, preparation, and biological activities of feruloyl derivatives of carbohydrates, glycerol and glycerides, amide, fatty alcohol, myo-inositol, and nitric oxide. It also briefly discussed other derivatives. Researchers are encouraged to carry out toxicological, pharmacokinetic, and clinical investigation of potent active feruloyl derivatives and to develop other derivatives.[5]
Reference
[1] Gray, S.G. and Ekström, T.J., 2001. The human histone deacetylase family. Experimental cell research, 262(2), pp.75-83.
[2] Dokmanovic, M., Clarke, C. and Marks, P.A., 2007. Histone deacetylase inhibitors: overview and perspectives. Molecular cancer research, 5(10), pp.981-989.
[3] Dokmanovic, M. and Marks, P.A., 2005. Prospects: histone deacetylase inhibitors. Journal of cellular biochemistry, 96(2), pp.293-304.
[4] Bautista, A.P.R., Sumalapao, D.E.P. and Villarante, N.R., 2017. Synthesis and characterization of epichlorohydrin-crosslinked lumbang (Aleurites moluccana)-derived activated carbon chitosan composite as Cr (VI) bioadsorbent. Annual Research & Review in Biology, pp.1-7.
[5] Pei, K., Ou, J., Huang, C. and Ou, S., 2015. Derivatives of ferulic acid: Structure, preparation and biological activities. Annual Research & Review in Biology, pp.512-528.
