Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Lipid Signaling, Lipidomics, and Vasculotoxicity Laboratory, Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Antioxid Redox Signal. 2012 Jul 15;17(2):327-39. doi: 10.1089/ars.2012.4600. Epub 2012 Apr 17.
In living systems, the mechanisms of inheritance involving gene expression are operated by (i) the traditional model of genetics where the deoxyribonucleic acid (DNA) transcription and messenger ribonucleic acid stability are influenced by the DNA sequences and any aberrations in the primary DNA sequences and (ii) the epigenetic (above genetics) model in which the gene expression is regulated by mechanisms other than the changes in DNA sequences. The widely studied epigenetic alterations include DNA methylation, covalent modification of chromatin structure, state of histone acetylation, and involvement of microribonucleic acids.
Currently, the role of cellular epigenome in health and disease is rapidly emerging. Several factors are known to modulate the epigenome-regulated gene expression that is crucial in several pathophysiological states and diseases in animals and humans. Phytochemicals have occupied prominent roles in human diet and nutrition as protective antioxidants in prevention/protection against several disorders and diseases in humans.
However, it is beginning to surface that the phytochemical phenolic antioxidants such as polyphenols, flavonoids, and nonflavonoid phenols function as potent modulators of the mammalian epigenome-regulated gene expression through regulation of DNA methylation, histone acetylation, and histone deacetylation in experimental models.
The antioxidant or pro-oxidant actions and their involvement in the epigenome regulation by the phytochemical phenolic antioxidants should be at least established in the cellular models under normal and pathophysiological states. The current review discusses the mechanisms of modulation of the mammalian cellular epigenome by the phytochemical phenolic antioxidants with implications in human diseases.
在生命系统中,涉及基因表达的遗传机制是通过(i)脱氧核糖核酸(DNA)转录和信使核糖核酸稳定性受 DNA 序列和初级 DNA 序列任何异常影响的传统遗传学模型,以及(ii)除 DNA 序列变化之外,基因表达受其他机制调控的表观遗传学(遗传学之上)模型来操作的。广泛研究的表观遗传改变包括 DNA 甲基化、染色质结构的共价修饰、组蛋白乙酰化状态以及 microRNA 的参与。
目前,细胞表观基因组在健康和疾病中的作用正在迅速显现。已知有几种因素可以调节表观基因组调控的基因表达,这在动物和人类的几种病理生理状态和疾病中至关重要。植物化学物质在人类饮食和营养中占据着重要地位,作为保护抗氧化剂,可预防/保护人类免受多种疾病的侵害。
然而,开始出现的情况是,植物化学类多酚抗氧化剂,如多酚、类黄酮和非类黄酮酚,通过调节 DNA 甲基化、组蛋白乙酰化和组蛋白去乙酰化,作为哺乳动物表观基因组调控基因表达的有效调节剂,在实验模型中发挥作用。
植物化学类多酚抗氧化剂的抗氧化或促氧化作用及其在表观基因组调控中的参与,至少应在正常和病理生理状态下的细胞模型中得到证实。本综述讨论了植物化学类多酚抗氧化剂对哺乳动物细胞表观基因组的调节机制及其在人类疾病中的意义。