Redox Signaling

Nanotechnology is a growing science that may provide several new applications for medicine, food preservation, diagnostic technologies, and sanitation. Despite its beneficial applications, there are several questions related to the safety of nanomaterials for human use. The development of nanotechnology is associated with some concerns because of the increased risk of carcinogenesis following exposure to nanomaterials. The increased levels of reactive oxygen species (ROS) that are due to exposure to nanoparticles (NPs) are primarily responsible for the genotoxicity of metal NPs. Not all, but most metal NPs are able to directly produce free radicals through the release of metal ions and through interactions with water molecules. Furthermore, the increased production of free radicals and the cell death caused by metal NPs can stimulate reduction/oxidation (redox) reactions, leading to the continuous endogenous production of ROS in a positive feedback loop. The overexpression of in-flammatory mediators, such as NF-kB and STATs, the mitochondrial malfunction and the increased intracellular calcium levels mediate the chronic oxidative stress that occurs after exposure to metal NPs. In this paper, we review the genotoxicity of different types of metal NPs and the redox mechanisms that amplify the toxicity of these NPs.

Molecular chaperones play key roles in protein quality control, signal transduction, proliferation, and cell death, and confer cytoprotection and assure survival after environmental stress. The heat-shock response is implicated in a variety of conditions including ischemic diseases, infection and immunity, neurodegeneration, and aging. Physiologic and pharmacologic chaperone inducers were shown to be an efficient therapeutic ap- proach in different acute

Continuous control of metabolism and developmental processes is a key feature of live cells. Cysteine thiol residues of proteins are both exceptionally useful in terms of structural and regulatory aspects, but at the same time exceptionally vulnerable to oxidation. Conserved cysteines thus are highly important for the function of metabolic enzymes and for signaling processes underlying responses to environmental factors. The underlying mechanism for the central role of thiol-mediated redox control in cellular metabolism is the ability of the cysteine-thiols to reversibly change their redox state followed by changes of structural, catalytic or regulatory functions. The cellular glutathione/glutathione disulfide redox buffer is present in cells at millimolar concentrations and forms one major basis of redox homeostasis by which protein thiols can maintain their redox state or oxidized protein thiols can be reverted to their reduced state. Besides acting as redox buffer, glutathione also acts as an electron donor for both scavenging of reactive oxygen, e.g. from photosynthesis and respiration, and metabolic reactions such as reduction of hydroperoxides and lipidperoxides or sulfate assimilation. The central role of glutathione is further emphasized by its involvement in signaling processes and the crosstalk of redox signaling processes with other means of signaling including protein glutathionylation and control of transcription factors. The present review aims at highlighting the key functions of glutathione in thiol-mediated redox control and its interplay with other protein-thiol-based redox systems.

This paper argues that “ASEA redox Supplement” (ARS) may show comparable or even stronger beneficial effects (with less or none adverse effects) than corticosteroids in children with Duchenne Muscular Dystrophy (DMD) and Becker muscular dystrophy (BMD). This paper presents a second case report on the effects of an ionized “saline water” called “ASEA redox Supplement®” (ARS) oral solution in a ~5-year-old boy with DMD from Bucharest, Romania. In vitro studies showed that ARS is a very potent selective NRF2 activator, thus a very potent (indirect) antioxidant and cytoprotective: the studies conducted in vivo also support this main pharmacological mechanism of ARS, with no toxicity up to high doses, in contrast with the much more toxic corticosteroids. From the first months of ARS treatment the main rhabdomyolysis markers (with very high initial serum levels) dropped significantly, with no found toxicity until present. The main conclusions of this second case report (on ARS effect in boys with DMD) are: (1) ARS has remarkable antioxidant and immunomodulatory effects and should be studied on larger groups of children with DMD under the age of 4 years old (but also on other age groups of children and even young adults), as an alternative to early corticosteroids; (2) Given its immunomodulatory effect (NRF2 selective activation and NF-kB inhibition), ARS deserves future cohort studies on its potential to replace corticosteroids and other non-steroidal immunosuppressants (at least partially) in many types of pulmonary/renal/hepatic/ articular/skin autoimmune and even malignant diseases of both children and adults; (3) Given its very strong antioxidant effects (by highly selective NRF2 potent activation), ARS deserves future cohort studies on acute/chronic diseases that imply high levels of tissular oxidative stress, especially some acute/chronic cardiovascular and respiratory diseases like acute myocardial infarction with acute/chronic heart failure, stroke, Chronic Obstructive Pulmonary Disease (COPD), asthma etc. of both children and adults (so that ARS may help millions and even billions worldwide). The latest version of this preprint is available at this URL: http://dragoii.com/ALDragoi_ASEA_in_DMD_2nd_case_latest.pdf This preprint is also available on Research Gate platform at this URL:
https://www.researchgate.net/publication/335502350

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The morbidity and mortality from coronary artery disease (CAD) remain significant worldwide. The treatment for acute
myocardial infarction has improved over the past decades, including early reperfusion of culprit coronary arteries. Although it
is mandatory to reperfuse the ischaemic territory as soon as possible, paradoxically this leads to additional myocardial injury,
namely ischaemia/reperfusion (I/R) injury, in which redox stress plays a pivotal role and for which no effective therapy is
currently available. In this review, we report evidence that the redox environment plays a pivotal role not only in I/R injury
but also in cardioprotection. In fact, cardioprotective strategies, such as pre- and post-conditioning, result in a robust
reduction in infarct size in animals and the role of redox signalling is of paramount importance in these conditioning
strategies. Nitrosative signalling and cysteine redox modifications, such as S-nitrosation/S-nitrosylation, are also emerging as
very important mechanisms in conditioning cardioprotection. The reasons for the switch from protective oxidative/nitrosative
signalling to deleterious oxidative/nitrosative/nitrative stress are not fully understood. The complex regulation of this switch is,
at least in part, responsible for the diminished or lack of cardioprotection induced by conditioning protocols observed in
ageing animals and with co-morbidities as well as in humans. Therefore, it is important to understand at a mechanistic level
the reasons for these differences before proposing a safe and useful transition of ischaemic or pharmacological conditioning.
Indeed, more mechanistic novel therapeutic strategies are required to protect the heart from I/R injury and to improve clinical
outcomes in patients with CAD.

Nowadays, using ionizing radiation (IR) is necessary for clinical, agricultural, nuclear energy or industrial applications. Accidental exposure to IR after a radiation terror or disaster poses a threat to human. In contrast to the old dogma of radiation toxicity, several experiments during the last two recent decades have revealed that intercellular signaling and communications play a key role in this procedure. Elevated level of cytokines and other intercellular signals increase oxidative damage and inflammatory responses via reduction/oxidation interactions (redox system). Intercellular signals induce production of free radicals and inflammatory mediators by some intermediate enzymes such as cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), NADPH oxidase, and also via triggering mitochondrial ROS. Furthermore, these signals facilitate cell to cell contact and increasing cell toxicity via cohort effect. Nitric oxide is a free radical with ability to act as an intercellular signal that induce DNA damage and changes in some signaling pathways in irradiated as well as non-irradiated adjacent cells. Targeting of these mediators by some anti-inflammatory agents or via antioxidants such as mitochondrial ROS scavengers opens a window to mitigate radiation toxicity after an accidental exposure. Experiments which have been done so far suggests that some cytokines such as IL-1β, TNF-α, TGF-β, IL-4 and IL-13 are some interesting targets that depend on irradiated organs and may help mitigate radiation toxicity. Moreover, animal experiments in recent years indicated that targeting of toll like receptors (TLRs) may be more useful for radioprotection and mitigation. In this review, we aimed to describe the role of intercellular interactions in oxidative injury, inflammation, cell death and killing effects of IR. Moreover, we described evidence on potential mitigation of radiation injury via targeting of these mediators.

Redox Signaling Molecules are essential to the healing process, and vital to nearly every aspect of our health and well-being. A balanced supply of RSMs insures that our cells, organs, and body systems can communicate with each other effectively and repair themselves when necessary. Because RSM production slows as we age, experience health challenges, or subject our bodies to stress, supplementing our internal reservoir of Redox Signaling Molecules is like turning back our cellular clock.

ASEA, the world’s first and only patented, stabilized Redox Signaling Supplement, is a balanced formulation of 16 Redox Signaling Molecules that are atomically identical to the ones inside our cells.

This is an exciting breakthrough. ASEA represents the first new category of natural health technology that I have observed in 30 years of holistically-oriented medical practice.

For more information contact me directly or go to http://MetaboliteMiracle.com

It has been reported that salicylic acid (SA) induces both immediate spike and long lasting phases of oxidative burst represented by the generation of reactive oxygen species (ROS) such as superoxide anion radical (O2
-). In general, in the earlier phase of oxidative burst, apoplastic peroxidase are likely involved and in the late phase of the oxidative burst, NADPH oxidase is likely involved. Key signaling events connecting the 2 phases of oxidative burst are calcium channel activation and protein phosphorylation events. To date, the known earliest signaling event in response to exogenously added SA is the cell wall peroxidase-catalyzed generation of O2
- in a hydrogen peroxide (H2O2)-dependent manner. However, this model is incomplete since the source of the initially required H2O2 could not be explained. Based on the recently proposed role for H2O2-independent mechanism for ROS production catalyzed by plant peroxidases (Kimura et al., 2014, Frontiers in Plant Science), we hereby propose a novel model for plant peroxidase-catalyzed oxidative burst fueled by SA.

A network of enzymatic and nonenzymatic antioxidants protects chloroplasts from photooxidative damage. With all enzymatic components being nuclear encoded, the control of the antioxidant capacity depends on chloroplast-to-nucleus redox signaling. Using an Arabidopsis (Arabidopsis thaliana) reporter gene line expressing luciferase under control of the redox-sensitive 2-cysteine peroxiredoxin A (2CPA) promoter, six mutants with low 2CPA promoter activity were isolated, of

There is a great deal of evidence that places oxidative stress as a proximal event in the natural history of Alzheimer disease (AD). In addition to increased damage, there are compensatory increases in the levels of free sulfhydryls, glucose-6-phosphate dehydrogenase, and NAD(P)H:quinone oxidoreductase 1. To investigate redox homeostasis further in AD, we analyzed protein disulfide isomerase (PDI), a multifunctional enzyme, which catalyzes the disruption and formation of disulfide bonds. PDI plays a pivotal role in both secreted and cell-surface-associated protein disulfide rearrangement. In this study, we show that PDI specifically localizes to neurons, where there is no substantial increase in AD compared to age-matched controls. These findings indicate that the neurons at risk of death in AD do not show a substantial change in PDI to compensate for the increased sulfhydryls and reductive state found during the disease. This suggests that, despite compensatory reductive changes in AD, the level of PDI is sufficiently high physiologically in neurons to accommodate a more reducing environment.

The violation of red signal are the major reasons for the occurrence of numerous accidents at intersections. An effort has been made to study the current rate of red signal violation in different road networks in Chennai which accounted for 18.27% and also to provide profile of red signal violation with various parameters. Road inventory survey was done at four selected intersections. The primary survey was conducted and 29743 samples were collected and analysed. The result of study provided scalable indicators for monitoring and evaluating road safety strategies to prevent red light violation in the country. The present research work also made an attempt to introduce an automatic traffic control system based on RFID technology and digital image processing. Then developed a prototype to identify red signal violation automatically with penalty system. These findings represent some useful reactions to improving road safety of urban functions in India and other developing countries.

Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS for macrophage-mediated immunity is unquestioned. Their functions comprise direct antimicrobial activity against bacteria and parasites as well as redox-regulation of immune signaling and induction of inflammasome activation. However, only a few studies have performed in-depth ROS analyses and even fewer have identified the precise redox-regulated target molecules. In this review , we will give a brief introduction to ROS and their sources in macrophages, summarize the versatile roles of ROS in direct and indirect antimicrobial immune defense, and provide an overview of commonly used ROS probes, scavengers and inhibitors. 1. Reactive Oxygen Species The term reactive oxygen species (ROS) describes a group of molecules with at least one oxygen atom and with higher reactivity than molecular oxygen (O2). This group consists of two subclasses: (I) highly reactive free radicals, including the superoxide an-ion (. O2 −), the hydroxyl radical (. OH), alkoxyl (. OOR) and peroxyl radicals (. OOH) [1-3] and (II) nonradical species such as hydrogen peroxide (H2O2), singlet oxygen (1 O2) [4,5], ozone (O3), and the hypochlorite anion (OCl −) [6,7]. ROS are produced by nearly all organisms and cells [8-12].. O2 − , the common precursor of all ROS produced by cells, is produced by single electron transfer to O2.. O2 − quickly dismutates to H2O2, either spontaneously in the presence of water or catalyzed by superoxide dismutases [13,14] (Figure 1). O2 − and H2O2 are the two most abundant ROS subspecies in cells, but highly differ in their chemical parameters and, therefore, in their behavior and function. O2 − shows higher reactivity than H2O2 and cannot cross cell membranes, except through ion channels, such as voltage-dependent anion channels (VDAC) [15]. An increase in. O2 − levels is associated with oxidative stress and cellular damage [16-19], such as oxidation of proteins [20-22], amino acids [23] and DNA [19,24] or lipid peroxidation [25-27]. Moreover,. O2 − can irreversibly inactivate proteins and thereby contribute to cellular signaling [28]. H2O2, as a diffusible and relatively stable molecule, is more suitable as a cellular signaling factor than. O2 − [29-33]. Although H2O2 is more diffusible than. O2 − , its diffusion over membranes is limited [34,35]. This questions the view of saturation of the cell with H2O2 to induce signaling pathways without regarding the compartment of ROS production [36,37]. Aquaporins allow a faster and controlled passage of H2O2 over membranes and add another regulatory level to ROS-mediated signaling [38,39]. The majority of Citation: Herb, M.; Schramm, M. Functions of ROS in Macrophages and Antimicrobial Immunity. Antioxidants 2021, 10, 313.