<p>Reactive Oxygen Species: Drivers of Physiological and Pathological Processes</p>

Abstract

Since the Great Oxidation Event, about 2.4 billion years ago, the Earth is immersed in an oxidizing atmosphere. Thus, it has been proposed that excess oxygen, originally a waste product of photosynthetic cyanobacteria, induced oxidative stress and the production of reactive oxygen species (ROS), which have since acted as fundamental drivers of biologic evolution and eukaryogenesis. Indeed, throughout an organism's lifespan, ROS affect directly (as mutagens) or indirectly (as messengers and regulators) all structural and functional components of cells, and many aspects of cell biology. Whether left unchecked by protective antioxidant systems, excess ROS not only cause genomic mutations but also induce irreversible oxidative modification of proteins (protein oxidation and peroxidation), lipids and glycans (advanced lipoxidation and glycation end products), impairing their function and promoting disease or cell death. Conversely, low-level local ROS play an important role both as redox-signaling molecules in a wide spectrum of pathways involved in the maintenance of cellular homeostasis (MAPK/ERK, PTK/PTP, PI3K-AKT-mTOR), and regulating key transcription factors (NFκB/IκB, Nrf2/KEAP1, AP-1, p53, HIF-1). Consequently, ROS can shape a variety of cellular functions, including proliferation, differentiation, migration and apoptosis. In this review, we will give a brief overview of the relevance of ROS in both physiological and pathological processes, particularly inflammation and aging. In-depth knowledge of the molecular mechanisms of ROS actuation and their influence under steady-state and stressful conditions will pave the way for the development of novel therapeutic interventions. This will mitigate the harmful outcomes of ROS in the onset and progression of a variety of chronic inflammatory and age-related diseases.

Glycolysis-induced drug resistance in tumors—A response to danger signals?

“…The first is DNA damage repair (DDR) [125] . DDR allows cells to avoid accumulation of DNA damages to a point that may lead to activation of mechanisms promoting the demise of the cell(s) [126] . Induction of DDR has been demonstrated for PGK1 [54] , PFKFB3 [48] , GLUT1 [41] , and lactate [83] .…”

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

“…Additionally, some herbicides, like glyphosate, 2,4-D and paraquat, at low dose, exert a hormetic response. When ROS are produced, H 2 O 2 acts as a signaling molecule that promotes cell walls malleability, allowing for inward water transport causing cell expansion [ 131 , 132 ].…”

“…Gradually, the production of ROS became a driver of physiological and pathological processes. Low-level ROS play an important role as redox-signaling molecules in a wide spectrum of pathways that are involved in the maintenance of cellular homeostasis and regulating key transcription factors (e.g., Nrf2/Keap1, NFκB/IκB, AP-1, p53, and HIF-1) [ 132 ].…”

Baicalin Improves Cardiac Outcome and Survival by Suppressing Drp1‐Mediated Mitochondrial Fission after Cardiac Arrest‐Induced Myocardial Damage

“…Evidence showed that mitochondria are not only the major site of ROS production but also the major targets of ROS under stress [ 39 ]. Excessive ROS production can trigger mitochondrial dysfunction including the decrease in ATP generation [ 40 ], damage of respiratory chain activity [ 41 ], promoting mitochondrial membrane permeabilization, and immediately followed by the release of cytochrome c [ 42 ]. Drp1-mediated mitochondrial fission has been demonstrated to involve mitochondrial ROS production during induced cell death [ 43 , 44 ].…”