Centre for Free Radical Research, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
Free Radic Biol Med. 2021 Jul;170:131-149. doi: 10.1016/j.freeradbiomed.2020.12.453. Epub 2021 Jan 12.
Excessive production of microbicidal oxidants by neutrophils can damage host tissue. The short-term response of cells to oxidative stress is well understood, but the mechanisms behind long-term consequences require further clarification. Epigenetic pathways mediate cellular adaptation, and are therefore a potential target of oxidative stress. Indeed, there is evidence that many proteins and metabolites involved in epigenetic pathways are redox sensitive. In this review we provide an overview of the epigenetic landscape and discuss the potential for redox regulation. Using this information, we highlight specific examples where neutrophil oxidants react with epigenetic pathway components. We also use published data from redox proteomics to map out known intersections between oxidative stress and epigenetics that may signpost helpful directions for future investigation. Finally, we discuss the role neutrophils play in adaptive pathologies with a focus on tumour initiation and progression. We hope this information will stimulate further discourse on the emerging field of redox epigenomics.
中性粒细胞产生过多的杀菌氧化剂会损害宿主组织。细胞对氧化应激的短期反应是众所周知的，但长期后果的机制仍需进一步阐明。表观遗传途径介导细胞适应，因此是氧化应激的潜在靶点。事实上，有证据表明，许多参与表观遗传途径的蛋白质和代谢物都是氧化还原敏感的。在这篇综述中，我们提供了一个表观遗传学景观的概述，并讨论了氧化还原调节的潜力。利用这些信息，我们强调了中性粒细胞氧化剂与表观遗传途径成分相互作用的具体例子。我们还使用来自氧化还原蛋白质组学的已发表数据，绘制出已知的氧化应激与表观遗传学之间的交叉点，这些交叉点可能为未来的研究指明有帮助的方向。最后，我们讨论了中性粒细胞在适应性病理学中的作用，重点是肿瘤的起始和进展。我们希望这些信息将进一步激发关于氧化还原表观基因组学这一新兴领域的讨论。
