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先天还是后天:让食物成为你治疗慢性炎症性疾病的表观遗传学药物。

Nature or nurture: let food be your epigenetic medicine in chronic inflammatory disorders.

机构信息

Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of Physiology, Ghent University, K.L. Ledeganckstraat 35, Gent, Belgium.

出版信息

Biochem Pharmacol. 2010 Dec 15;80(12):1816-32. doi: 10.1016/j.bcp.2010.07.029. Epub 2010 Aug 3.

Abstract

Numerous clinical, physiopathological and epidemiological studies have underlined the detrimental or beneficial role of nutritional factors in complex inflammation related disorders such as allergy, asthma, obesity, type 2 diabetes, cardiovascular disease, rheumatoid arthritis and cancer. Today, nutritional research has shifted from alleviating nutrient deficiencies to chronic disease prevention. It is known that lifestyle, environmental conditions and nutritional compounds influence gene expression. Gene expression states are set by transcriptional activators and repressors and are often locked in by cell-heritable chromatin states. Only recently, it has been observed that the environmental conditions and daily diet can affect transgenerational gene expression via "reversible" heritable epigenetic mechanisms. Epigenetic changes in DNA methylation patterns at CpG sites (epimutations) or corrupt chromatin states of key inflammatory genes and noncoding RNAs, recently emerged as major governing factors in cancer, chronic inflammatory and metabolic disorders. Reciprocally, inflammation, metabolic stress and diet composition can also change activities of the epigenetic machinery and indirectly or directly change chromatin marks. This has recently launched re-exploration of anti-inflammatory bioactive food components for characterization of their effects on epigenome modifying enzymatic activities (acetylation, methylation, phosphorylation, ribosylation, oxidation, ubiquitination, sumoylation). This may allow to improve healthy aging by reversing disease prone epimutations involved in chronic inflammatory and metabolic disorders.

摘要

许多临床、生理病理和流行病学研究都强调了营养因素在过敏、哮喘、肥胖、2 型糖尿病、心血管疾病、类风湿性关节炎和癌症等复杂炎症相关疾病中的有害或有益作用。如今,营养研究已经从缓解营养缺乏转变为慢性疾病预防。众所周知,生活方式、环境条件和营养化合物会影响基因表达。基因表达状态由转录激活因子和转录抑制因子设定,并且通常被细胞遗传的染色质状态锁定。直到最近,人们才观察到环境条件和日常饮食可以通过“可逆”的遗传表观遗传机制影响跨代基因表达。CpG 位点 DNA 甲基化模式(表观突变)或关键炎症基因和非编码 RNA 的染色质状态的表观遗传变化,最近成为癌症、慢性炎症和代谢紊乱的主要调控因素。反过来,炎症、代谢应激和饮食成分也可以改变表观遗传机制的活性,并间接或直接改变染色质标记。这最近重新探索了抗炎生物活性食物成分,以研究它们对表观基因组修饰酶活性(乙酰化、甲基化、磷酸化、核糖基化、氧化、泛素化、SUMO 化)的影响。这可能通过逆转涉及慢性炎症和代谢紊乱的疾病易感表观突变来改善健康衰老。

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