Ogle Meredith M, Trevino Rolando, Schell Joseph, Varmazyad Mahboubeh, Horikoshi Nobuo, Gius David
Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, 7979 Wurzbach Road, San Antonio, TX 78229, USA.
Joe R. & Teresa Lozano Long School of Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Antioxidants (Basel). 2022 Mar 25;11(4):635. doi: 10.3390/antiox11040635.
The loss and/or dysregulation of several cellular and mitochondrial antioxidants' expression or enzymatic activity, which leads to the aberrant physiological function of these proteins, has been shown to result in oxidative damage to cellular macromolecules. In this regard, it has been surmised that the disruption of mitochondrial networks responsible for maintaining normal metabolism is an established hallmark of cancer and a novel mechanism of therapy resistance. This altered metabolism leads to aberrant accumulation of reactive oxygen species (ROS), which, under specific physiological conditions, leads to a potential tumor-permissive cellular environment. In this regard, it is becoming increasingly clear that the loss or disruption of mitochondrial oxidant scavenging enzymes may be, in specific tumors, either an early event in transformation or exhibit tumor-promoting properties. One example of such an antioxidant enzyme is manganese superoxide dismutase (MnSOD, also referred to as SOD2), which detoxifies superoxide, a ROS that has been shown, when its normal physiological levels are disrupted, to lead to oncogenicity and therapy resistance. Here, we will also discuss how the acetylation of MnSOD leads to a change in detoxification function that leads to a cellular environment permissive for the development of lineage plasticity-like properties that may be one mechanism leading to tumorigenic and therapy-resistant phenotypes.
几种细胞和线粒体抗氧化剂的表达或酶活性丧失和/或失调，导致这些蛋白质的生理功能异常，已被证明会导致细胞大分子的氧化损伤。在这方面，有人推测，负责维持正常代谢的线粒体网络的破坏是癌症的一个既定标志，也是治疗耐药的一种新机制。这种代谢改变导致活性氧（ROS）异常积累，在特定生理条件下，会导致潜在的肿瘤许可细胞环境。在这方面，越来越清楚的是，线粒体氧化清除酶的丧失或破坏在特定肿瘤中可能是转化的早期事件，或者具有促肿瘤特性。这种抗氧化酶的一个例子是锰超氧化物歧化酶（MnSOD，也称为SOD2），它能清除超氧化物，这是一种ROS，当其正常生理水平被破坏时，已被证明会导致致癌性和治疗耐药性。在这里，我们还将讨论MnSOD的乙酰化如何导致解毒功能的变化，从而导致一种有利于发展谱系可塑性样特性的细胞环境，这可能是导致肿瘤发生和治疗耐药表型的一种机制。
