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肠道干细胞代谢、命运和功能中的活性氧物种。

Reactive Oxygen Species in intestinal stem cell metabolism, fate and function.

机构信息

Immunology Discovery, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.

Immunology Discovery, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA; Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945-1400, USA.

出版信息

Free Radic Biol Med. 2021 Apr;166:140-146. doi: 10.1016/j.freeradbiomed.2021.02.015. Epub 2021 Feb 15.

Abstract

Long dismissed as merely harmful respiratory by-products, Reactive Oxygen Species (ROS) have emerged as critical intracellular messengers during cell growth and differentiation. ROS's signaling roles are particularly prominent within the intestine, whose high regenerative capacity is maintained by Intestinal Stem Cells (ISCs). In this review, we outline roles for ROS in ISCs as revealed by studies using Drosophila and mouse model systems. We focus particularly on recent studies highlighting how ROS ties to metabolic adaptations, which ensure energy supply matches demand during ISC activation and differentiation. We describe how declines in these adaptive mechanisms, through aging or pathology, promote reciprocal changes in ISC metabolism and ROS signaling. These changes ultimately contribute to aberrant ISC function, a loss of tissue homeostasis, and a shortened lifespan.

摘要

长期以来,活性氧(ROS)被认为只是有害的呼吸副产物,但在细胞生长和分化过程中,ROS 已成为关键的细胞内信使。ROS 的信号作用在肠道中尤为突出,肠道的高再生能力是由肠干细胞(ISCs)维持的。在这篇综述中,我们通过使用果蝇和小鼠模型系统的研究,概述了 ROS 在 ISCs 中的作用。我们特别关注最近的研究,这些研究强调了 ROS 如何与代谢适应相关联,以确保在 ISC 激活和分化过程中能量供应与需求相匹配。我们描述了这些适应性机制如何随着衰老或病变而衰退,从而促进 ISC 代谢和 ROS 信号的相互变化。这些变化最终导致 ISC 功能异常、组织内稳态丧失和寿命缩短。

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