Chemistry, physiology and pathology of free radicals

The superoxide anion radical and other reactive oxygen species (ROS) are formed in all aerobic organisms by enzymatic and nonenzymatic reactions. ROS arise in both physiological and pathological processes, but efficient mechanisms have evolved for their detoxification. Similarly, reactive nitrogen intermediates (RNI) have physiological activity, but can also react with different types of molecules, including superoxide, to form toxic products. ROS and RNI participate in the destruction of microorganisms by phagocytes, as in the formation of a myeloperoxidase-hydrogen peroxide-chloride/iodide complex which can destroy many cells, including bacteria. It is known that the cellular production of ROS and RNI is controlled by different mechanisms. These free radicals can react with key cellular structures and molecules, thus altering their biological function. An imbalance between the systems producing and removing ROS and RNI may result in pathological consequences.     

Physiological polyamines: simple primordial stress molecules

Physiological polyamines are ubiquitous polycations with pleiotropic biochemical activities, including regulation of gene expression, cell proliferation and modulation of cell signalling. Reports that the polyamines with cytoprotective activities were induced by diverse stresses raised the hypothesis that physiological polyamines may play a role in inducing stress response. In a wide range of organisms, physiological polyamines were not only induced by diverse stresses, such as reactive oxygen species (ROS), heat, ultraviolet (UV) and psychiatric stress but were able to confer beneficial effects for survival. Recent biochemical and genetic evidences show that polyamines can function as an ROS scavenger, acid tolerance factor and chemical chaperone, and positive regulators for expression of stress response genes which may explain their protective functions against diverse stresses. Taken together, these data suggest that physiological polyamines can function as primordial stress molecules in bacteria, plants and mammals, and may play an essential role in regulation of pathogen-host interactions.     

严格厌氧菌铁氧还蛋白的研究进展

铁氧还蛋白(ferredoxin,Fd)是一类含有铁硫簇的小分子蛋白质,广泛存在于自然界中,参与生物体内的呼吸、发酵、固氮、二氧化碳固定和制氢等生理过程.Fd对于严格厌氧的细菌尤为重要,是因为这类细菌的能量代谢高度依赖于低氧化还原电势的生物组分,而Fd能够利用铁硫中心灵活调节其氧还电势,适应低电势需求.本文选取厌氧细菌...     

Reactive Oxygen Species: Potential Regulatory Molecules in Response to Hypomagnetic Field Exposure

Organisms, including humans, could be exposed to hypomagnetic fields (HMFs, intensity <5 μT), e.g. in some artificially shielded magnetic environments and during deep-space flights. Previous studies have demonstrated that HMF exposure could have negative effects on the central nervous system and embryonic development in many animals. However, the underlying mechanisms remain unknown. Studies have revealed that HMFs affect cellular reactive oxygen species (ROS) levels and thereby alter physiological and biological processes in organisms. ROS, the major component of highly active free radicals, which are ubiquitous in biological systems, were hypothesized to be the candidate signaling molecules that regulate diverse physiological processes in response to changes in magnetic fields. Here, we summarize the recent advances in the study of HMF-induced negative effects on the central nervous system and early embryonic development in animals, focusing on cellular ROS and their role in response to HMFs. Furthermore, we discuss the potential mechanism through which HMFs regulate ROS levels in cells. © 2020 Bioelectromagnetics Society     

Redox signaling mediated by the gut microbiota

Abstract

The microbiota that occupies the mammalian intestine can modulate a range of physiological functions, including control over immune responses, epithelial barrier function, and cellular proliferation. While commensal prokaryotic organisms are well known to stimulate inflammatory signaling networks, less is known about control over homeostatic pathways. Recent work has shown that gut epithelia contacted by enteric commensal bacteria rapidly generate reactive oxygen species (ROS). While the induced production of ROS in professional phagocytes via stimulation of formyl peptide receptors (FPRs) and activation of NADPH oxidase 2 (Nox2) is a well-studied process, ROS are also similarly elicited in other cell types, including intestinal epithelia, in response to microbial signals via FPRs and the epithelial NADPH oxidase 1 (Nox1). ROS generated by Nox enzymes have been shown to function as critical second messengers in multiple signal transduction pathways via the rapid and transient oxidative inactivation of a distinct class of sensor proteins bearing oxidant-sensitive thiol groups. These redox-sensitive proteins include tyrosine phosphatases that serve as regulators of MAP kinase pathways, focal adhesion kinase, as well as components involved in NF-κB activation. As microbe-elicited ROS has been shown to stimulate cellular proliferation and motility, and to modulate innate immune signaling, we hypothesize that many of the established effects of the normal microbiota on intestinal physiology may be at least partially mediated by this ROS-dependent mechanism.     

Redox Regulation of Apoptosis before and after Cytochrome C Release

Programmed cell death, or apoptosis, is one of the most studied areas of modern biology. Apoptosis is a genetically regulated process, which plays an essential role in the development and homeostasis of higher organisms. Mitochondria, known to play a central role in regulating cellular metabolism, was found to be critical for regulating apoptosis induced under both physiological and pathological conditions. Mitochondria are a major source of reactive oxygen species (ROS) but they can also serve as its target during the apoptosis process. Release of apoptogenic factors from mitochondria, the best known of which is cytochrome c, leads to assembly of a large apoptosis-inducing complex called the apoptosome. Cysteine proteases (called caspases) are recruited to this complex and, following their activation by proteolytic cleavage, activate other caspases, which in turn target for specific cleavage a large number of cellular proteins. The redox regulation of apoptosis during and after cytochrome c release is an area of intense investigation. This review summarizes what is known about the biological role of ROS and its targets in apoptosis with an emphasis on its intricate connections to mitochondria and the basic components of cell death.     

HEAVY METAL–INDUCED OXIDATIVE STRESS IN ALGAE1

Heavy metals, depending on their oxidation states, can be highly reactive and, as a consequence, toxic to most organisms. They are produced by an expanding variety of anthropogenic sources suggesting an increasingly important role for this form of pollution. The toxic effect of heavy metals appears to be related to production of reactive oxygen species (ROS) and the resulting unbalanced cellular redox status. Algae respond to heavy metals by induction of several antioxidants, including diverse enzymes such as superoxide dismutase, catalase, glutathione peroxidase and ascorbate peroxidase, and the synthesis of low molecular weight compounds such as carotenoids and glutathione. At high, or acute, levels of metal pollutants, damage to algal cells occurs because ROS levels exceed the capacity of the cell to cope. At lower, or chronic, levels algae accumulate heavy metals and can pass them on to organisms of other trophic levels such as mollusks, crustaceans, and fishes. We review here the evidence linking metal accumulation, cellular toxicity, and the generation of ROS in aquatic environments.     

细菌响应过量活性氧的存活策略及相关研究进展

活性氧(Reactive Oxygen Species,ROS)是指基态氧分子获取电子后形成的一类具有高反应活性的物质.有氧呼吸电子传递链产生的内源ROS能维持细菌正常生理活性,而由消毒、抗生素和物理场等处理产生的外源ROS会随着处理时间和强度增加而累积产生.过量ROS会给细菌带来氧化压力,导致氧化损伤,甚至影响其活性...     

Protein oxidation and cellular homeostasis: Emphasis on metabolism

Reactive oxygen species (ROS) are generated as the result of a number of physiological and pathological processes. Once formed ROS can promote multiple forms of oxidative damage, including protein oxidation, and thereby influence the function of a diverse array of cellular processes. This review summarizes the mechanisms by which ROS are generated in a variety of cell types, outlines the mechanisms which control the levels of ROS, and describes specific proteins which are common targets of ROS. Additionally, this review outlines cellular processes which can degrade or repair oxidized proteins, and ultimately describes the potential outcomes of protein oxidation on cellular homeostasis. In particular, this review focuses on the relationship between elevations in protein oxidation and multiple aspects of cellular metabolism. Together, this review describes a potential role for elevated levels of protein oxidation contributing to cellular dysfunction and oxidative stress via impacts on cellular metabolism.     

NO and ROS implications in the organization of root system architecture

Over the past decades the role of nitric oxide (NO) and reactive oxygen species (ROS) in signaling and cellular responses to stress has witnessed an exponential trend line. Despite advances in the subject, our knowledge of the role of NO and ROS as regulators of stress and plant growth and their implication in signaling pathways is still partial. The crosstalk between NO and ROS during root formation offers new domains to be explored, as it regulates several plant functions. Previous findings indicate that plants utilize these signaling molecules for regulating physiological responses and development. Depending upon cellular concentration, NO either can stimulate or impede root system architecture (RSA) by modulating enzymes through post-translational modifications. Similarly, the ROS signaling molecule network, in association with other hormonal signaling pathways, control the RSA. The spatial regulation of ROS controls cell growth and ROS determine primary root and act in concert with NO to promote lateral root primordia. NO and ROS are two central messenger molecules which act differentially to upregulate or downregulate the expression of genes pertaining to auxin synthesis and to the configuration of root architecture. The investigation concerning the contribution of donors and inhibitors of NO and ROS can further aid in deciphering their role in root development. With this background, this review provides comprehensive details about the effect and function of NO and ROS in the development of RSA.     

Life-history Constraints on the Mechanisms that Control the Rate of ROS Production

The quest to understand why and how we age has led to numerous lines of investigation that have gradually converged to consider mitochondrial metabolism as a major player. During mitochondrial respiration a small and variable amount of the consumed oxygen is converted to reactive species of oxygen (ROS). For many years, these ROS have been perceived as harmful by-products of respiration. However, evidence from recent years indicates that ROS fulfill important roles as cellular messengers. Results obtained using model organisms suggest that ROS-dependent signalling may even activate beneficial cellular stress responses, which eventually may lead to increased lifespan. Nevertheless, when an overload of ROS cannot be properly disposed of, its accumulation generates oxidative stress, which plays a major part in the ageing process. Comparative studies about the rates of ROS production and oxidative damage accumulation, have led to the idea that the lower rate of mitochondrial oxygen radical generation of long-lived animals with respect to that of their short-lived counterpart, could be a primary cause of their slow ageing rate. A hitherto largely under-appreciated alternative view is that such lower rate of ROS production, rather than a cause may be a consequence of the metabolic constraints imposed for the large body sizes that accompany high lifespans. To help understanding the logical underpinning of this rather heterodox view, herein I review the current literature regarding the mechanisms of ROS formation, with particular emphasis on evolutionary aspects.     

Reactive oxygen species in colorectal cancer: The therapeutic impact and its potential roles in tumor progression via perturbation of cellular and physiological dysregulated pathways

Reactive oxygen species (ROS) are produced by mitochondria during metabolism. In physiological states, the production of ROS and their elimination by antioxidants are kept in balance. However, in pathological states, elevated levels of ROS interact with susceptible cellular target compounds including lipids, proteins, and DNA and deregulate oncogenic signaling pathways that are involved in colorectal cancer (CRC) carcinogenesis. Although antioxidant compounds have been successfully used in the treatment of CRC as prevention approaches, they have also been shown in some cases to promote disease progression. In this review, we focus on the role of ROS in gastrointestinal homeostasis, CRC progression, diagnosis, and therapy with particular emphasis on ROS-stimulated pathways.     

Reactive oxygen species and temperature stresses: A delicate balance between signaling and destruction

Temperature stress can have a devastating effect on plant metabolism, disrupting cellular homeostasis, and uncoupling major physiological processes. A direct result of stress-induced cellular changes is the enhanced accumulation of toxic compounds in cells that include reactive oxygen species (ROS). Although a considerable amount of work has shown a direct link between ROS scavenging and plant tolerance to temperature stress, recent studies have shown that ROS could also play a key role in mediating important signal transduction events. Thus, ROS, such as superoxide (O₂^–), are produced by NADPH oxidases during abiotic stress to activate stress-response pathways and induce defense mechanisms. The rates and cellular sites of ROS production during temperature stress could play a central role in stress perception and protection. ROS levels, as well as ROS signals, are thought to be controlled by the ROS gene network of plants. It is likely that in plants this network is interlinked with the different networks that control temperature stress acclimation and tolerance. In this review paper, we attempt to summarize some of the recent studies linking ROS and temperature stress in plants and propose a model for the involvement of ROS in temperature stress sensing and defense.     

NADPH oxidases contribute to autophagy regulation

Reactive oxygen species (ROS) are emerging as regulators of autophagy in various cellular contexts. There are many cellular sources of ROS in eukaryotic cells. In phagocytes, the critical immune cells for host defense, the Nox2 NADPH oxidase generates ROS during phagocytosis and plays a central role in microbial killing. Toll-like receptors (TLRs) are important membrane microbial sensing receptors, which can activate Nox2,¹ and were recently demonstrated to signal autophagy targeting of phagosomes to promote their maturation.² Our recent study reveals that Nox2 activity and its generated ROS are key signals that induce TLR-activated autophagy of phagosomes. Our results provide the first evidence that ROS from the Nox2 NADPH oxidase can contribute to regulating autophagy in host defense against bacteria. The association of TLR, Nox2 and autophagy with inflammatory bowel disease (IBD) suggests a significant role of this antibacterial pathway in these diseases.     

Extracellular ATP in plants. Visualization, localization, and analysis of physiological significance in growth and signaling

Extracellular ATP (eATP) in animals is well documented and known to play an important role in cellular signaling (e.g. at the nerve synapse). The existence of eATP has been postulated in plants; however, there is no definitive experimental evidence for its presence or an explanation as to how such a polar molecule could exit the plant cell and what physiological role it may play in plant growth and development. The presence of eATP in plants (Medicago truncatula) was detected by constructing a novel reporter; i.e. fusing a cellulose-binding domain peptide to the ATP-requiring enzyme luciferase. Application of this reporter to plant roots allowed visualization of eATP in the presence of the substrate luciferin. Luciferase activity could be detected in the interstitial spaces between plant epidermal cells and predominantly at the regions of actively growing cells. The levels of eATP were closely correlated with regions of active growth and cell expansion. Pharmacological compounds known to alter cytoplasmic calcium levels revealed that ATP release is a calcium-dependent process and may occur through vesicular fusion, an important step in the polar growth of actively growing root hairs. Reactive oxygen species (ROS) activity at the root hair tip is not only essential for root hair growth, but also dependent on the cytoplasmic calcium levels. Whereas application of exogenous ATP and a chitin mixture increased ROS activity in root hairs, no changes were observed in response to adenosine, AMP, ADP, and nonhydrolyzable ATP (betagammameATP). However, application of exogenous potato (Solanum tuberosum) apyrase (ATPase) decreased ROS activity, suggesting that cytoplasmic calcium gradients and ROS activity are closely associated with eATP release.     

Mitochondrial reactive oxygen species-mediated signaling in endothelial cells

Once thought of as toxic by-products of cellular metabolism, reactive oxygen species (ROS) have been implicated in a large variety of cell-signaling processes. Several enzymatic systems contribute to ROS production in vascular endothelial cells, including NA(D)PH oxidase, xanthine oxidase, uncoupled endothelial nitric oxide synthase, and the mitochondrial electron transport chain. The respiratory chain is the major source of ROS in most mammalian cells, but the role of mitochondria-derived ROS in vascular cell signaling has received little attention. A new paradigm has evolved in recent years postulating that, in addition to producing ATP, mitochondria also play a key role in cell signaling and regulate a variety of cellular functions. This review focuses on the emerging role of mitochondrial ROS as signaling molecules in vascular endothelial cells. Specifically, we discuss some recent findings that indicate that mitochondrial ROS regulate vascular endothelial function, focusing on major sites of ROS production in endothelial mitochondria, factors modulating mitochondrial ROS production, the physiological and clinical implications of endothelial mitochondrial ROS, and methodological considerations in the study of mitochondrial contribution to vascular ROS generation.     

Role of peroxynitrite in the responses induced by heat stress in tobacco BY-2 cultured cells

Temperatures above the optimum are sensed as heat stress (HS) by all living organisms and represent one of the major environmental challenges for plants. Plants can cope with HS by activating specific defense mechanisms to minimize damage and ensure cellular functionality. One of the most common effects of HS is the overproduction of reactive oxygen and nitrogen species (ROS and RNS). The role of ROS and RNS in the regulation of many plant physiological processes is well established. On the contrary, in plants very little is known about the physiological role of peroxynitrite (ONOO^?), the RNS species generated by the interaction between NO and O₂^?. In this work, the role of ONOO^? on some of the stress responses induced by HS in tobacco BY-2 cultured cells has been investigated by measuring these responses both in the presence and in the absence of 2,6,8-trihydroxypurine (urate), a specific scavenger of ONOO^?. The obtained results suggest a potential role for ONOO^? in some of the responses induced by HS in tobacco cultured cells. In particular, ONOO^? seems implicated in a form of cell death showing apoptotic features and in the regulation of the levels of proteins involved in the response to stress.     

Superoxide dismutase 1 knock-down induces senescence in human fibroblasts

Reactive oxygen species (ROS) such as superoxide radicals are responsible for the pathogenesis of various human diseases. ROS are generated during normal metabolic process in all of the oxygen-utilizing organisms. The copper-zinc-containing SOD (SOD1) acts as a major defense against ROS by detoxifying the superoxide anion. In model organisms, SOD1 has been shown to play a role in the aging process. However, the exact role of the SOD1 protein in the human aging process remains to be resolved. We show that SOD1 RNA interference (RNAi) induces senescence in normal human fibroblasts. This premature senescence depends on p53 induction. In contrast, in human fibroblastic cells with inactivated p53, the SOD1 RNAi is without effect. Surprisingly, in cancer cells (HeLa), the SOD1 RNAi induces cell death rather then senescence. Together, these findings support the notion that in normal human cells the SOD1 protein may play a role in the regulation of cellular lifespan by p53 and may also regulate the death signals in cancer cells.