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免疫系统与内皮细胞代谢重编程的相似性。

Similarities in the Metabolic Reprogramming of Immune System and Endothelium.

作者信息

Tang Chu-Yik, Mauro Claudio

机构信息

Barts and The London School of Medicine and Dentistry, Institute of Health Sciences Education, Queen Mary University of London, London, United Kingdom.

Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.

出版信息

Front Immunol. 2017 Jul 21;8:837. doi: 10.3389/fimmu.2017.00837. eCollection 2017.

Abstract

Cellular metabolism has been known for its role in bioenergetics. In recent years, much light has been shed on the reprogrammable cellular metabolism underlying many vital cellular processes, such as cell activation, proliferation, and differentiation. Metabolic reprogramming in immune and endothelial cells (ECs) is being studied extensively. These cell compartments are implicated in inflammation and pathogenesis of many diseases but their similarities in metabolic reprogramming have not been analyzed in detail. One of the most notable metabolic reprogramming is the Warburg-like effect, famously described as one of the hallmarks of cancer cells. Immune cells and ECs can display this phenotype that is characterized by a metabolic switch favoring glycolysis over oxidative phosphorylation (OXPHOS) in aerobic conditions. Though energy-inefficient, aerobic glycolysis confers many benefits to the respiring cells ranging from higher rate of adenosine triphosphate production to maintaining redox homeostasis. Chemical and biological regulators either promote or perturb this effect. In this review, nitric oxide, hypoxia-inducible factor, and adenosine monophosphate-activated protein kinase have been discussed for their common involvement in metabolic reprogramming of both systems. From and animal studies, various discrepancies exist regarding the effects of those regulators on metabolic switch. However, it is generally accepted that glycolysis favors inflammatory reactions while OXPHOS favors anti-inflammatory processes. The reasons for such observation are currently subject of intense studies and not completely understood. Finally, metabolic reprogramming in immune cells and ECs does not limit to the physiological state in health but can also be observed in pathological states, such as atherosclerosis and cancer. These new insights provide us with a better understanding of the similarities in metabolic reprogramming across a number of cell types, which could pave the way for future research and possible metabolic-based therapeutics.

摘要

细胞代谢因其在生物能量学中的作用而为人所知。近年来,许多重要细胞过程(如细胞激活、增殖和分化)背后的可重编程细胞代谢已得到充分阐明。免疫细胞和内皮细胞(ECs)中的代谢重编程正在被广泛研究。这些细胞区室与许多疾病的炎症和发病机制有关,但其在代谢重编程方面的相似性尚未得到详细分析。最显著的代谢重编程之一是瓦伯格样效应,它被著名地描述为癌细胞的标志之一。免疫细胞和内皮细胞可以表现出这种表型,其特征是在有氧条件下代谢转向有利于糖酵解而非氧化磷酸化(OXPHOS)。尽管有氧糖酵解能量效率低下,但它赋予呼吸细胞许多益处,从更高的三磷酸腺苷产生速率到维持氧化还原稳态。化学和生物调节剂要么促进要么干扰这种效应。在这篇综述中,讨论了一氧化氮、缺氧诱导因子和腺苷单磷酸激活蛋白激酶在这两个系统代谢重编程中的共同参与。从体外和动物研究来看,这些调节剂对代谢转换的影响存在各种差异。然而,人们普遍认为糖酵解有利于炎症反应,而氧化磷酸化有利于抗炎过程。这种观察结果的原因目前是深入研究的主题,尚未完全理解。最后,免疫细胞和内皮细胞中的代谢重编程不仅限于健康状态下的生理状态,在病理状态(如动脉粥样硬化和癌症)中也能观察到。这些新见解使我们更好地理解了多种细胞类型在代谢重编程方面的相似性,这可能为未来的研究和基于代谢的治疗方法铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8854/5519526/7189e7ea14e7/fimmu-08-00837-g001.jpg

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