Ultraviolet-B (UV-B) radiation has long been perceived as a stressor. However, a conceptual U-turn has taken place, and UV-B damage is now considered rare. We question whether UV-stress and ...UV-B-induced reactive oxygen species (ROS) are still relevant concepts, and if ROS-mediated signaling contributes to UV-B acclimation. Measurements of antioxidants and of antioxidant genes show that both low and high UV-B doses alter ROS metabolism. Yet, there is no evidence that ROS control gene expression under low UV-B. Instead, expression of antioxidant genes is linked to the UV RESISTANCE LOCUS 8 pathway. We hypothesize that low UV-B doses cause ‘eustress’ (good stress) and that stimuli-specific signaling pathways pre-dispose plants to a state of low alert that includes activation of antioxidant defenses.
Nanoparticles can potentially stimulate tumour microenvironments to elicit antitumour immunity. Herein, we demonstrate effective immunotherapy of colorectal cancer via systemic delivery of an ...immunostimulatory chemotherapeutic combination in nanoscale coordination polymer (NCP) core-shell particles. Oxaliplatin and dihydroartemesinin have contrasting physicochemical properties but strong synergy in reactive oxygen species (ROS) generation and anticancer activity. The combined ROS generation is harnessed for immune activation to synergize with an anti-PD-L1 antibody for the treatment of murine colorectal cancer tumours. The favourable biodistribution and tumour uptake of NCPs and the absence of peripheral neuropathy allow for repeated dosing to afford 100% tumour eradication. The involvement of innate and adaptive immune systems elicit strong and long lasting antitumour immunity which prevents tumour formation when cured mice are challenged with cancer cells. The intrinsically biodegradable, well tolerated, and systemically available immunostimulatory NCP promises to enter clinical testing as an immunotherapy against colorectal cancer.
Recently, it was proposed that there is a common mechanism behind the activity of bactericidal antibiotics, involving the production of reactive oxygen species (ROS). However, the involvement of ROS ...in antibiotic-mediated killing has become the subject of much debate. In the present review, we provide an overview of the data supporting the ROS hypothesis; we also present data that explain the contradictory results often obtained when studying antibiotic-induced ROS production. For this latter aspect we will focus on the importance of taking the experimental setup into consideration and on the importance of some technical aspects of the assays typically used. Finally, we discuss the link between ROS production and toxin–antitoxin modules, and present an overview of implications for treatment.
Reactive oxygen species (ROS) play an integral role as signalling molecules in the regulation of numerous biological processes such as growth, development, and responses to biotic and/or abiotic ...stimuli in plants. To some extent, various functions of ROS signalling are attributed to differences in the regulatory mechanisms of respiratory burst oxidase homologues (RBOHs) that are involved in a multitude of different signal transduction pathways activated in assorted tissue and cell types under fluctuating environmental conditions. Recent findings revealed that stress responses in plants are mediated by a temporal–spatial coordination between ROS and other signals that rely on production of stress-specific chemicals, compounds, and hormones. In this review we will provide an update of recent findings related to the integration of ROS signals with an array of signalling pathways aimed at regulating different responses in plants. In particular, we will address signals that confer systemic acquired resistance (SAR) or systemic acquired acclimation (SAA) in plants.
The mitochondrial respiratory chain is a major source of reactive oxygen species (ROS) in eukaryotic cells. Mitochondrial ROS production associated with a dysfunction of respiratory chain complexes ...has been implicated in a number of degenerative diseases and biological aging. Recent findings suggest that mitochondrial ROS can be integral components of cellular signal transduction as well. Within the respiratory chain, complexes I (NADH:ubiquinone oxidoreductase) and III (ubiquinol:cytochrome c oxidoreductase; cytochrome bc (1) complex) are generally considered as the main producers of superoxide anions that are released into the mitochondrial matrix and the intermembrane space, respectively. The primary function of both respiratory chain complexes is to employ energy supplied by redox reactions to drive the vectorial transfer of protons into the mitochondrial intermembrane space. This process involves a set of distinct electron carriers designed to minimize the unwanted leak of electrons from reduced cofactors onto molecular oxygen and hence ROS generation under normal circumstances. Nevertheless, it seems plausible that superoxide is derived from intermediates of the normal catalytic cycles of complexes I and III. Therefore, a detailed understanding of the molecular mechanisms driving these enzymes is required to understand mitochondrial ROS production during oxidative stress and redox signalling. This review summarizes recent findings on the chemistry and control of the reactions within respiratory complexes I and III that result in increased superoxide generation. Regulatory contributions of other components of the respiratory chain, especially complex II (succinate:ubiquinone oxidoreductase) and the redox state of the ubiquinone pool (Q-pool) will be briefly discussed.
Upon reaction with electrons, oxygen is transformed into reactive oxygen species (ROS). It has long been known that ROS can destroy bacteria and destroy human cells, but research in recent decades ...has highlighted new roles for ROS in health and disease. Indeed, while prolonged exposure to high ROS concentrations may lead to non-specific damage to proteins, lipids, and nucleic acids, low to intermediate ROS concentrations exert their effects rather through regulation of cell signalling cascades. Biological specificity is achieved through the amount, duration, and localisation of ROS production. ROS have crucial roles in normal physiological processes, such as through redox regulation of protein phosphorylation, ion channels, and transcription factors. ROS are also required for biosynthetic processes, including thyroid hormone production and crosslinking of extracellular matrix. There are multiple sources of ROS, including NADPH oxidase enzymes; similarly, there are a large number of ROS-degrading systems. ROS-related disease can be either due to a lack of ROS (e.g., chronic granulomatous disease, certain autoimmune disorders) or a surplus of ROS (e.g., cardiovascular and neurodegenerative diseases). For diseases caused by a surplus of ROS, antioxidant supplementation has proven largely ineffective in clinical studies, most probably because their action is too late, too little, and too non-specific. Specific inhibition of ROS-producing enzymes is an approach more promising of clinical efficacy.
Elevated levels of reactive oxygen species (ROS) are a hallmark of cancer. Although increased ROS concentrations play important roles in cancer formation and progression, levels above a cytotoxic ...threshold cause cancer cell death. Cancer cells adapt to high concentrations of ROS via antioxidant production and reprogrammed cellular metabolism (eg, the Warburg effect). Because some widely used anticancer therapies such as radiation therapy and chemotherapy rely on ROS accumulation as a mechanism to induce cancer cell death, a cancer cell's ability to control ROS levels is a driver of treatment resistance and a critical consideration for successful cancer treatment. The necessity for cancer cells to adapt to elevated levels of ROS to survive may represent an Achilles heel for some malignancies, as therapies designed to interfere with this adaptation would be expected to kill cancer cells. In this review, we provide an overview of the implications of ROS on cancer formation and anticancer treatment strategies, with a focus on treatment-resistant disease.
'Reactive oxygen species' (ROS) is a generic term that defines a wide variety of oxidant molecules with vastly different properties and biological functions that range from signalling to causing cell ...damage. Consequently, the description of oxidants needs to be chemically precise to translate research on their biological effects into therapeutic benefit in redox medicine. This Expert Recommendation article pinpoints key issues associated with identifying the physiological roles of oxidants, focusing on H
O
and O
. The generic term ROS should not be used to describe specific molecular agents. We also advocate for greater precision in measurement of H
O
, O
and other oxidants, along with more specific identification of their signalling targets. Future work should also consider inter-organellar communication and the interactions of redox-sensitive signalling targets within organs and whole organisms, including the contribution of environmental exposures. To achieve these goals, development of tools that enable site-specific and real-time detection and quantification of individual oxidants in cells and model organisms are needed. We also stress that physiological O
levels should be maintained in cell culture to better mimic in vivo redox reactions associated with specific cell types. Use of precise definitions and analytical tools will help harmonize research among the many scientific disciplines working on the common goal of understanding redox biology.
Redox homeostasis is an essential requirement of the biological systems for performing various normal cellular functions including cellular growth, differentiation, senescence, survival and aging in ...humans. The changes in the basal levels of reactive oxygen species (ROS) are detrimental to cells and often lead to several disease conditions including cardiovascular, neurological, diabetes and cancer. During the last two decades, substantial research has been done which clearly suggests that ROS are essential for the initiation, progression, angiogenesis as well as metastasis of cancer in several ways. During the last two decades, the potential of dysregulated ROS to enhance tumor formation through the activation of various oncogenic signaling pathways, DNA mutations, immune escape, tumor microenvironment, metastasis, angiogenesis and extension of telomere has been discovered. At present, surgery followed by chemotherapy and/or radiotherapy is the major therapeutic modality for treating patients with either early or advanced stages of cancer. However, the majority of patients relapse or did not respond to initial treatment. One of the reasons for recurrence/relapse is the altered levels of ROS in tumor cells as well as in cancer-initiating stem cells. One of the critical issues is targeting the intracellular/extracellular ROS for significant antitumor response and relapse-free survival. Indeed, a large number of FDA-approved anticancer drugs are efficient to eliminate cancer cells and drug resistance by increasing ROS production. Thus, the modulation of oxidative stress response might represent a potential approach to eradicate cancer in combination with FDA-approved chemotherapies, radiotherapies as well as immunotherapies.
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