Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution

Abstract

Since the evolution of the aerobic metabolism, reactive oxygen species (ROS) have represented significant challenges to diverse life forms. In recent decades, increasing knowledge has revealed a dual role for ROS in cell physiology, showing they serve as a major source of cellular damage while also functioning as important signaling molecules in various biological processes. Our understanding of ROS homeostasis and ROS-mediated cellular signaling pathways has presumed that they are ancient and highly conserved mechanisms shared by most organisms. However, emerging evidence highlights the complexity and plasticity of ROS signaling, particularly in animals that have evolved in extreme environments. In this review, we focus on ROS generation, antioxidative systems and the main signaling pathways that are influenced by ROS. In addition, we discuss ROS’s responsive transcription regulation and how it may have been shaped over the course of evolution.

Unraveling the Role of Reactive Oxygen Species in T Lymphocyte Signaling

“…Free thiol groups in NF-κB subunits are also oxidized in the cytosolic milieu, with thioredoxin (TRX)-1 primarily reversing this process in the nucleus (Figure 6). Notably, NF-κB must be in its reduced form in the nucleus to effectively bind to DNA binding sites [29,90,108,109]. NF-AT is primarily regulated by Ca 2+ .…”

“…Oxidation of this thiol group by H 2 O 2 leads to PTP inactivation. Given the reversibility of PTP oxidation, these proteins exist in two alternative states: an active state with a reduced cysteine or an inactive state with an oxidized cysteine [ 9 , 90 ]. ROS generated upon TCR stimulation rapidly convert to H 2 O 2 , which constitutes the primary oxidative signal.…”

“…These kinases are activated via phosphorylation and deactivated by dephosphorylation through MAPK phosphatases (MKPs). The activation-induced oxidative signal inactivates MKPs, thereby activating MAPKs ( Figure 5 ) such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK), and p38, inducing cell proliferation and differentiation [ 90 , 91 , 92 ]. Another critical regulator of T cell activation and function is the Phosphatase and Tensin Homolog (PTEN).…”

“…Again, the MAPK signaling pathway is the most prominent example in T cells. Activation of MAPKs typically involves a cascade of kinase reactions, progressing from MAP kinase kinase kinases (MAPKKKs) to MAP kinase kinases (MAPKKs), culminating in the final activation of MAPK [ 90 , 92 , 94 ]. ROS-induced oxidation of free thiol groups activates MAPKKKs, promoting kinase activity through conformational changes [ 95 , 96 ].…”

Cytotoxic Cu(II) Complexes with a Novel Quinoline Derivative Ligand: Synthesis, Molecular Docking, and Biological Activity Analysis

“…Copper metal ions are important in cell division and growth and accumulating research evidence supports its potential utility in the battle against cancer . Copper-based complexes have also been studied for their direct free radical scavenging abilities, demonstrating their potential to mitigate the harmful effects of oxidative stress. , Copper can also enhance the effectiveness of some chemotherapeutic drugs like bioactive organic ligands by sensitizing cancer cells. This synergistic effect can improve the overall efficacy of cancer therapy …”