Bassett Shalome A, Barnett Matthew P G
Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch Limited, Grasslands Research Centre, Tennent Drive, Palmerston North 4442, New Zealand.
Nutrients. 2014 Oct 15;6(10):4273-301. doi: 10.3390/nu6104273.
Modification of the histone proteins associated with DNA is an important process in the epigenetic regulation of DNA structure and function. There are several known modifications to histones, including methylation, acetylation, and phosphorylation, and a range of factors influence each of these. Histone deacetylases (HDACs) remove the acetyl group from lysine residues within a range of proteins, including transcription factors and histones. Whilst this means that their influence on cellular processes is more complex and far-reaching than histone modifications alone, their predominant function appears to relate to histones; through deacetylation of lysine residues they can influence expression of genes encoded by DNA linked to the histone molecule. HDAC inhibitors in turn regulate the activity of HDACs, and have been widely used as therapeutics in psychiatry and neurology, in which a number of adverse outcomes are associated with aberrant HDAC function. More recently, dietary HDAC inhibitors have been shown to have a regulatory effect similar to that of pharmacological HDAC inhibitors without the possible side-effects. Here, we discuss a number of dietary HDAC inhibitors, and how they may have therapeutic potential in the context of a whole food.
与DNA相关的组蛋白修饰是DNA结构和功能表观遗传调控中的一个重要过程。已知组蛋白有多种修饰,包括甲基化、乙酰化和磷酸化,并且一系列因素会影响其中的每一种修饰。组蛋白去乙酰化酶(HDACs)会从包括转录因子和组蛋白在内的多种蛋白质中的赖氨酸残基上去除乙酰基。虽然这意味着它们对细胞过程的影响比单独的组蛋白修饰更为复杂和深远,但其主要功能似乎与组蛋白有关;通过赖氨酸残基的去乙酰化,它们可以影响与组蛋白分子相连的DNA所编码基因的表达。HDAC抑制剂反过来会调节HDACs的活性,并且已在精神病学和神经病学中广泛用作治疗药物,在这些领域中,许多不良后果与HDAC功能异常有关。最近,已证明膳食HDAC抑制剂具有与药理学HDAC抑制剂类似的调节作用,且没有可能的副作用。在此,我们讨论一些膳食HDAC抑制剂,以及它们在全食物背景下可能具有的治疗潜力。