Namakkal-Soorappan Rajasekaran
Cardiac Aging & Redox Signaling Laboratory, Division of Molecular & Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL35294, USA.
Division of Cardiovascular Medicine, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
React Oxyg Species (Apex). 2017 Sep 1;4(11):298-302. doi: 10.20455/ros.2017.849.
About three decades of intensive research suggest that tumor necrosis factor-alpha (TNF-α) is a "miscreant". Although it is obvious that supra-physiological TNF-α levels are deleterious to cellular activities leading to a variety of pathological conditions, it is unlikely that complete removal of TNF-α is cytoprotective. Are we rejecting the basal physiological role of TNF-α as a reactive oxygen species (ROS) producer that is key and essential for numerous basal cell signaling processes? We believe that there are important protective roles for TNF-α under basal/physiological conditions. We propose that one such role is that of signaling through nuclear erythroid 2 p45 related factor-2/antioxidant response element (Nrf2/ARE). Confirming our hypothesis that TNF-α is necessary and sufficient for the basal activation of Nrf2/ARE transcriptional pathways, will change the existing paradigms on the function of TNF-α. This article briefly reviews the canonical role of TNF-α as miscreant and introduces a new role as a hero in the context of Nrf2-antioxidant signaling.
约三十年的深入研究表明，肿瘤坏死因子-α（TNF-α）是个“捣蛋鬼”。虽然超生理水平的TNF-α对细胞活动有害，会导致多种病理状况这一点很明显，但完全去除TNF-α不太可能具有细胞保护作用。我们是否在否定TNF-α作为活性氧（ROS）产生者的基础生理作用，而ROS对众多基础细胞信号传导过程至关重要？我们认为，TNF-α在基础/生理条件下具有重要的保护作用。我们提出，其中一个作用是通过核红细胞2 p45相关因子2/抗氧化反应元件（Nrf2/ARE）进行信号传导。证实我们关于TNF-α对Nrf2/ARE转录途径的基础激活既必要又充分的假设，将改变现有的关于TNF-α功能的范式。本文简要回顾了TNF-α作为捣蛋鬼的典型作用，并介绍了其在Nrf2-抗氧化信号传导背景下作为英雄的新角色。
