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氧化作用与红细胞生成。

Oxidation and erythropoiesis.

机构信息

Department of Medicine, University Hospital of Verona, Azienda Ospedaliera Universitaria Integrata (AOUI) Verona, Verona, Italy.

出版信息

Curr Opin Hematol. 2019 May;26(3):145-151. doi: 10.1097/MOH.0000000000000495.

Abstract

PURPOSE OF REVIEW

Erythropoiesis is a complex multistep process going from committed erythroid progenitors to mature red cells. Although recent advances allow the characterization of some components of erythropoiesis, much still remains to be investigated particularly on stress erythropoiesis. This review summarizes recent progresses made to understand the impact of oxidative stress on normal and pathologic erythropoiesis.

RECENT FINDINGS

During erythroid maturation, reactive oxygen species might function as second messenger through either transient oxidation of cysteine residues on signaling targets or modulation of intracellular signaling pathways. Thus, in erythropoiesis, efficient cytoprotective systems are required to limit possible reactive oxygen species-related toxic effects especially in stress erythropoiesis characterized by severe oxidation such as β-thalassemia. In addition, prolonged or severe oxidative stress impairs autophagy, which might contribute to the block of erythroid maturation in stress erythropoiesis. Understanding the functional role of cytoprotective systems such as peroxiredoxin-2 or classical molecular chaperones such as the heat shock proteins will contribute to develop innovative therapeutic strategies for ineffective erythropoiesis.

SUMMARY

We provide an update on cytoprotective mechanisms against oxidation in normal and stress erythropoiesis. We discuss the role of oxidative sensors involved in modulation of intracellular signaling during erythroid maturation process in normal and stress erythropoiesis.

摘要

目的综述

红细胞生成是一个复杂的多步骤过程,从定向造血祖细胞到成熟红细胞。尽管最近的进展允许对红细胞生成的某些成分进行特征描述,但仍有许多需要研究,特别是在应激性红细胞生成方面。本篇综述总结了目前对氧化应激对正常和病理性红细胞生成影响的理解进展。

最近的发现

在红细胞成熟过程中,活性氧可能作为第二信使,通过信号靶标上半胱氨酸残基的瞬时氧化或细胞内信号通路的调节来发挥作用。因此,在红细胞生成中,需要有效的细胞保护系统来限制可能的与活性氧相关的毒性作用,特别是在β-地中海贫血等以严重氧化为特征的应激性红细胞生成中。此外,长期或严重的氧化应激会损害自噬,这可能导致应激性红细胞生成中红细胞成熟的阻滞。了解细胞保护系统(如过氧化物酶 2)或经典分子伴侣(如热休克蛋白)的功能作用将有助于为无效红细胞生成开发创新的治疗策略。

总结

我们提供了关于正常和应激性红细胞生成中抗氧化保护机制的最新信息。我们讨论了在正常和应激性红细胞生成中,氧化传感器在调节红细胞成熟过程中细胞内信号中的作用。

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