Recent advances in iron homeostasis and regulation - a focus on epigenetic regulation and stroke
Recent advances in iron homeostasis and regulation - a focus on epigenetic regulation and stroke
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DOI：
10.1080/10715762.2020.1867314
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发表时间：
2020-12
影响因子：
3.3
通讯作者：
Honglian Shi;Mohammed M. A. Almutairi;J. Moskovitz;Yuexia Xu
中科院分区：
文献类型：
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作者：
Honglian Shi;Mohammed M. A. Almutairi;J. Moskovitz;Yuexia Xu
摘要铁是一种具有氧化还原性质的元素。它是许多酶的活性位点，在多种细胞和生物功能中起着重要作用，包括ATP的产生和DNA的合成。然而，作为氧化还原元素，铁促进自由基生成和脂质过氧化，引起氧化损伤和细胞死亡。铁介导的氧化在铁凋亡中起核心作用，铁凋亡是一种不同于细胞凋亡和坏死的细胞死亡过程。因此，铁的代谢和体内平衡受到复杂的调节。自从hepcidin被认为是铁稳态的中央调节剂以来，对铁代谢和调节的理解取得了令人兴奋的进展。Hepcidin主要调控铁渗透酶铁转运蛋白的铁输出功能，铁转运蛋白是目前已知唯一由哺乳动物细胞表达的铁输出蛋白。特别是，表观遗传调控已成为最近关注的铁稳态。表观遗传现象已被证明可以调节铁代谢中的关键蛋白，包括hepcidin。在这里，我们回顾了近年来在理解铁稳态的分子机制方面的快速进展，重点是hepcidin，铁蛋白和铁凋亡的表观遗传调控。讨论了蛋氨酸氧化与铁的相互作用。此外，许多研究表明，脑卒中后神经元损伤的严重程度与脑铁积累的大小成正比。本文简要讨论了脑卒中中铁代谢的最新发现。了解铁调节的潜在机制可以为包括中风在内的各种顽固性疾病的治疗提供见解。
Abstract Iron is an element with redox properties. It is active sites of many enzymes and plays an important role in various cellular and biological functions including ATP production and DNA synthesis. However, as a redox element, iron promotes free radical generation and lipid peroxidation, causing oxidative damage and cell death. Iron-mediated oxidation is a central player in ferroptosis, a type of cell death process that is different from apoptosis and necrosis. Thus, iron metabolism and homeostasis are sophisticatedly regulated. There has been exciting progress in understanding iron metabolism and regulation since hepcidin was recognized as the central regulator of iron homeostasis. Hepcidin mainly regulates the iron export function of the ferrous iron permease, ferroportin, which is the only known iron exporter expressed by mammalian cells. Particularly, epigenetic regulation has been a recent focus on iron homeostasis. Epigenetic phenomena have been demonstrated to modulate key proteins including hepcidin in iron metabolism. Here, we review the rapid progress in recent years in understanding molecular mechanisms of iron homeostasis with a focus on epigenetic regulation of hepcidin, ferritin, and ferroptosis. Interactions between methionine oxidation and iron is also discussed. Furthermore, many studies have suggested that the severity of neuronal damage after stroke is proportional to the magnitude of brain iron accumulation. Recent discoveries regarding iron metabolism in stroke is briefly discussed. Understanding the underlying mechanism in iron regulation could provide insight into the treatment of various intractable diseases including stroke.