<br>脯氨酰 4-羟化酶活性响应转录因子：从羟基化到基因表达和神经保护。,Frontiers in Bioscience

当前位置： X-MOL 学术 › Front Biosci › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

脯氨酰 4-羟化酶活性响应转录因子：从羟基化到基因表达和神经保护。
Frontiers in Bioscience Pub Date : 2008-01-01 , DOI: 10.2741/2892
Ambreena Siddiq ₁ , Leila R Aminova , Rajiv R Ratan

Affiliation

大多数稳态过程（包括基因转录）都是由于威胁生物体生存的生理音调偏差而发生的。典型的稳态应激反应包括氧、铁或 2-酮戊二酸水平改变后基因表达的变化。这些辅助因子中的每一个都在细胞代谢中发挥着重要作用。因此，被称为脯氨酰 4-羟化酶 (PHD) 的酶家族是一组双加氧酶，它们已进化为通过酶活性的变化来感知 2-酮戊二酸、氧和铁的变化。事实上，PHD 是已建立的氧传感器系统的一部分，该系统调节缺氧/应激调节基因的转录调节，因此是导致细胞从氧、铁或 2-酮戊二酸剥夺中解救的事件的重要组成部分。 PHD 活性调节对氧、铁或 2-酮戊二酸代谢的稳态反应的能力导致了 PHD 小分子抑制剂的开发，作为激活或增强细胞应激反应的策略。这些小分子在中风和帕金森病的临床前模型中被证明是有效的。然而，PHD 抑制所涉及的精确保护途径才刚刚开始被确定。在当前的综述中，我们总结了铁、2-酮戊二酸和氧在 PHD 催化的羟基化反应中的作用，并简要讨论了一些转录因子，这些转录因子在神经保护中发挥有效作用，防止氧化应激（由于氧化应激的变化）。博士活动。

"点击查看英文标题和摘要"

Prolyl 4-hydroxylase activity-responsive transcription factors: from hydroxylation to gene expression and neuroprotection.

Most homeostatic processes including gene transcription occur as a result of deviations in physiological tone that threatens the survival of the organism. A prototypical homeostatic stress response includes changes in gene expression following alterations in oxygen, iron or 2-oxoglutarate levels. Each of these cofactors plays an important role in cellular metabolism. Accordingly, a family of enzymes known as the Prolyl 4-hydroxylase (PHD) enzymes are a group of dioxygenases that have evolved to sense changes in 2-oxoglutarate, oxygen and iron via changes in enzyme activity. Indeed, PHDs are a part of an established oxygen sensor system that regulates transcriptional regulation of hypoxia/stress-regulated genes and thus are an important component of events leading to cellular rescue from oxygen, iron or 2-oxoglutarate deprivations. The ability of PHD activity to regulate homeostatic responses to oxygen, iron or 2-oxoglutarate metabolism has led to the development of small molecule inhibitors of the PHDs as a strategy for activating or augmenting cellular stress responses. These small molecules are proving effective in preclinical models of stroke and Parkinson's disease. However the precise protective pathways engaged by PHD inhibition are only beginning to be defined. In the current review, we summarize the role of iron, 2-oxoglutarate and oxygen in the PHD catalyzed hydroxylation reaction and provide a brief discussion of some of the transcription factors that play an effective role in neuroprotection against oxidative stress as a result of changes in PHD activity.

更新日期：2019-11-01

点击分享查看原文

点击收藏

公开下载