Phytochemical antioxidants modulate mammalian cellular epigenome: implications in health and disease.
Phytochemical antioxidants modulate mammalian cellular epigenome: implications in health and disease.
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DOI：
10.1089/ars.2012.4600
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发表时间：
2012-07
影响因子：
6.6
通讯作者：
Smitha Malireddy;S. Kotha;J. Secor;Travis O. Gurney;J. Abbott;G. Maulik;K. Maddipati;N. Parinandi
中科院分区：
文献类型：
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作者：
Smitha Malireddy;S. Kotha;J. Secor;Travis O. Gurney;J. Abbott;G. Maulik;K. Maddipati;N. Parinandi
在生命系统中，涉及基因表达的遗传机制是通过（i）传统的遗传学模型来操作的，其中脱氧核糖核酸（DNA）转录和信使核糖核酸稳定性受到DNA序列和初级DNA序列中的任何畸变的影响，以及（ii）表观遗传学模型。基因表达受DNA序列变化以外的机制调节的（高于遗传学）模型。广泛研究的表观遗传学改变包括DNA甲基化、染色质结构的共价修饰、组蛋白乙酰化状态和微核糖核酸的参与。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。已知几种因子调节表观基因组调节的基因表达，这在动物和人类的几种病理生理状态和疾病中是至关重要的。植物化学物质在人类饮食和营养中作为保护性抗氧化剂在预防/保护人类免受几种疾病和病症中占据了突出的作用。最近的进展然而，它开始浮出水面，植物化学酚类抗氧化剂，如多酚类，类黄酮，和nonflavonoid酚作为有效的调节剂的哺乳动物表观基因组调控的基因表达，通过调节DNA甲基化，组蛋白乙酰化，组蛋白去乙酰化的实验模型。关键问题和未来的发展方向的抗氧化剂或促氧化剂的行动和参与表观基因组调控的植物化学酚类抗氧化剂应至少建立在正常和病理生理状态下的细胞模型。本文综述了植物酚类抗氧化剂对哺乳动物细胞表观基因组的调控机制及其对人类疾病的影响。
UNLABELLED 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. SIGNIFICANCE 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. RECENT ADVANCES 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. CRITICAL ISSUES AND FUTURE DIRECTIONS 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.