An Innovative Hydrogen Peroxide-Sensing Scaffold and Insights Towards its Potential as an ROS-Activated Persulfide Donor

2020 ◽  
Author(s):  
Rynne Hankins ◽  
S. Israel Suarez ◽  
Madison Kalk ◽  
Nolan Green ◽  
Megan Harty ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Initial Rate ◽  
Therapeutic Potential ◽  
Oxygen Species ◽  
Sulfur Species ◽  
Cellular Protection ◽  
Severe Limitation ◽  
Strategic Implementation

Reactive sulfur species, such as hydrogen sulfide, persulfides, and polysulfides, have recently emerged as key signaling molecules and important physiological mediators within mammalian systems. To further assess the therapeutic potential of their exogenous administration, we report on the development of a unique hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-sensing motif and its capacity for providing cellular protection against oxidative stress while serving as a reactive oxygen species (ROS)-activated persulfide donor. With the strategic implementation of a <i>gem</i>-dimethyl group that promotes both cyclization and stability, we found the initial rate of payload release from this newly derived scaffold to be directly proportional to the concentration of H<sub>2</sub>O<sub>2</sub> and to proceed via an unprecedented pathway that avoids the production of electrophilic byproducts, a severe limitation that has plagued the physiological application of previous designs.

scholarly journals An Innovative Hydrogen Peroxide-Sensing Scaffold and Insights Towards its Potential as an ROS-Activated Persulfide Donor

2020 ◽  
Author(s):  
Rynne Hankins ◽  
S. Israel Suarez ◽  
Madison Kalk ◽  
Nolan Green ◽  
Megan Harty ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Initial Rate ◽  
Therapeutic Potential ◽  
Oxygen Species ◽  
Sulfur Species ◽  
Cellular Protection ◽  
Severe Limitation ◽  
Strategic Implementation

Reactive sulfur species, such as hydrogen sulfide, persulfides, and polysulfides, have recently emerged as key signaling molecules and important physiological mediators within mammalian systems. To further assess the therapeutic potential of their exogenous administration, we report on the development of a unique hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-sensing motif and its capacity for providing cellular protection against oxidative stress while serving as a reactive oxygen species (ROS)-activated persulfide donor. With the strategic implementation of a <i>gem</i>-dimethyl group that promotes both cyclization and stability, we found the initial rate of payload release from this newly derived scaffold to be directly proportional to the concentration of H<sub>2</sub>O<sub>2</sub> and to proceed via an unprecedented pathway that avoids the production of electrophilic byproducts, a severe limitation that has plagued the physiological application of previous designs.

scholarly journals Intracellular Sources of ROS/H2O2 in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 233
Author(s):  
Tasuku Konno ◽  
Eduardo Pinho Melo ◽  
Joseph E. Chambers ◽  
Edward Avezov
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Endoplasmic Reticulum ◽  
Neurodegenerative Diseases ◽  
Antioxidative Enzymes ◽  
Redox Reactions ◽  
Ros Production ◽  
Oxygen Species ◽  
Specific Target

Reactive oxygen species (ROS) are produced continuously throughout the cell as products of various redox reactions. Yet these products function as important signal messengers, acting through oxidation of specific target factors. Whilst excess ROS production has the potential to induce oxidative stress, physiological roles of ROS are supported by a spatiotemporal equilibrium between ROS producers and scavengers such as antioxidative enzymes. In the endoplasmic reticulum (ER), hydrogen peroxide (H2O2), a non-radical ROS, is produced through the process of oxidative folding. Utilisation and dysregulation of H2O2, in particular that generated in the ER, affects not only cellular homeostasis but also the longevity of organisms. ROS dysregulation has been implicated in various pathologies including dementia and other neurodegenerative diseases, sanctioning a field of research that strives to better understand cell-intrinsic ROS production. Here we review the organelle-specific ROS-generating and consuming pathways, providing evidence that the ER is a major contributing source of potentially pathologic ROS.

scholarly journals Novel Antioxidant Properties of Doxycycline

2018 ◽  
Vol 19 (12) ◽  
pp. 4078 ◽  
Author(s):  
Dahn Clemens ◽  
Michael Duryee ◽  
Cleofes Sarmiento ◽  
Andrew Chiou ◽  
Jacob McGowan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Chronic Inflammation ◽  
Antioxidant Properties ◽  
Antibacterial Properties ◽  
Reactive Oxygen ◽  
Protein Adducts ◽  
Oxygen Species ◽  
Free System

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen species (ROS) produced during the formation of MAA-adducts and inhibits the formation of MAA-protein adducts. To determine whether DOX scavenges specific ROS, we examined the ability of DOX to directly scavenge superoxide and hydrogen peroxide. Using electron paramagnetic resonance (EPR) spectroscopy, we found that DOX directly scavenged superoxide, but not hydrogen peroxide. Additionally, we found that DOX inhibits MAA-induced activation of Nrf2, a redox-sensitive transcription factor. Together, these findings demonstrate the under-recognized direct antioxidant property of DOX that may help to explain its therapeutic potential in the treatment of conditions characterized by chronic inflammation and increased oxidative stress.

scholarly journals Caffeic Acid - Potential Antioxidant in Cultured Human Retinal Pigment Epithelial Cells

1970 ◽  
Vol 66 (2) ◽  
Author(s):  
Dumitriţa RUGINǍ ◽  
Adela PINTEA ◽  
Raluca PÂRLOG ◽  
Andreea VARGA
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Protective Effect ◽  
Caffeic Acid ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Antioxidant Defence ◽  
Rpe Cells ◽  
In Cells

Oxidative stress causes biological changes responsible for carcinogenesis and aging in human cells. The retinal pigmented epithelium is continuously exposed to oxidative stress. Therefore reactive oxygen species (ROS) and products of lipid peroxidation accumulate in RPE. Neutralization of ROS occurs in retina by the action of antioxidant defence systems. In the present study, the protective effect of caffeic acid (3,4-dihydroxy cinnamic acid), a dietary phenolic compound, has been examined in normal and in oxidative stress conditions (500 µM peroxide oxygen) in cultures human epithelial pigment retinal cells (Nowak, M. et al.). The cell viability, the antioxidant enzymes activity (CAT, GPx, SOD) and the level of intracellular reactive oxygen species (ROS) were determined. Exposure to l00 µM caffeic acid for 24 h induced cellular changes indicating the protective effect of caffeic acid in RPE cells. Caffeic acid did not show any cytotoxic effect at concentrations lower than 200 μM in culture medium. Treatment of RPE cells with caffeic acid causes an increase of catalase, glutathione peroxidase and superoxide dismutase activity, especially in cells treated with hydrogen peroxide. Caffeic acid causes a decrease of ROS level in cells treated with hydrogen peroxide. This study proved that caffeic acid or food that contain high levels of this phenolic acid may have beneficial effects in prevention of retinal diseases associated with oxidative stress by improving antioxidant defence systems.

scholarly journals Sources of ROS Species an Its Harmful and Benefical Effects on Human Health

2021 ◽  
Author(s):  
Sidra Munir
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Antioxidant Enzymes ◽  
Immune System ◽  
Cardiovascular Diseases ◽  
Partial Oxidation ◽  
Human Body ◽  
Therapeutic Potential ◽  
Oxygen Species ◽  
Essential Function

When the antioxidants in our immune system cannot neutralize or convert Reactive oxygen species into safe molecules at the rate at which it is produced then this imbalance is termed as &ldquo;oxidative stress&rdquo;. It is related with a wide array of diseases that includes cancer, diabetes, cardiovascular diseases, hypertension etc. These ROS species however are utmost essential for the proper functioning of human body which are produced as a consequence of partial oxidation of cellular metabolism performing essential functions such as protein phosphorylation, activation of several transcriptional factors, apoptosis, immunity, and differentiation. The sources by which these are produced can be broadly classified are intrinsic and extrinsic sources. There are variety of natural antioxidant enzymes of human body that combat against this oxidative stress. The extrinsic sources of ROS include the use of natural plants, extracted flavonoids and vitamins. In this review we will briefly explain how the sources of ROS, its essential function in human body, its elevation and associated damage to organs and effect on various diseases, and a hope of finding a way of how this oxidative stress can be exploited for therapeutic potential.

Oxidative stress and cardiovascular health: therapeutic potential of polyphenols

2013 ◽  
Vol 91 (3) ◽  
pp. 198-212 ◽  
Author(s):  
Sandhya Khurana ◽  
Matthew Piche ◽  
Amanda Hollingsworth ◽  
Krishnan Venkataraman ◽  
T.C. Tai
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Recent Progress ◽  
Cardiovascular Health ◽  
Therapeutic Potential ◽  
Cellular Function ◽  
Oxygen Species ◽  
The Impact ◽  
Detrimental Impact ◽  
Normal Cellular Function

Reactive oxygen species (ROS) are important in normal cellular function and physiology. However, oxidative stress resulting from an accumulation of ROS has a detrimental impact on cellular function, and ROS has been implicated in the pathogenesis of a number of diseases, including cardiovascular diseases. This review provides a summary of the impact of ROS on cardiovascular health and diseases, highlighting the therapeutic use of antioxidants. In addition, this review summarizes the health benefits of polyphenols, and the recent progress on understanding the cellular and physiological actions by which polyphenols may impart their beneficial properties on cardiovascular health.

scholarly journals Distinct Signaling Pathways Respond to Arsenite and Reactive Oxygen Species in Schizosaccharomyces pombe

2005 ◽  
Vol 4 (8) ◽  
pp. 1396-1402 ◽  
Author(s):  
Miguel A. Rodríguez-Gabriel ◽  
Paul Russell
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Schizosaccharomyces Pombe ◽  
Stress Responses ◽  
Biological Effects ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Increased Risk ◽  
Risk Of Cancer

ABSTRACT Exposure to certain metal and metalloid species, such as arsenic, cadmium, chromium, and nickel, has been associated with an increased risk of cancer in humans. The biological effects of these metals are thought to result from induction of reactive oxygen species (ROS) and inhibition of DNA repair enzymes, although alterations in signal transduction pathways may also be involved in tumor development. To better understand metal toxicity and its connection to ROS, we have compared the effects of arsenite and hydrogen peroxide in wild-type and mutant strains of the fission yeast Schizosaccharomyces pombe. An atf1Δ pap1Δ strain, which is defective in two transcription factors that control stress responses, is extremely sensitive to hydrogen peroxide but not to arsenite. A strain that lacks the transcription factor Zip1 has the opposite relationship. Spc1 (Sty1) mitogen-activated protein kinase (MAPK), a homologue of mammalian p38 MAPK, and the upstream MAPK kinase (MAPKK) Wis1 are essential for survival of both arsenite and hydrogen peroxide. Inactivation of two MAPKK kinases, Win1 and Wis4, almost completely eliminates Spc1 activation by arsenite, yet these cells survive arsenite treatment. The two-component phosphorelay protein Mcs4, which acts upstream of Win1 and Wis4 and is required for Spc1 activation in response to oxidative stress, is not required for Spc1 activation in response to arsenite. We conclude that the toxic effects of arsenic are not strongly connected to oxidative stress and that although Spc1 is activated by arsenic exposure, the basal activity of Spc1 is largely sufficient for the survival of arsenic.

scholarly journals The antimicrobial action of polyaniline involves production of oxidative stress while functionalisation of polyaniline introduces additional mechanisms

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5135 ◽  
Author(s):  
Julia Robertson ◽  
Marija Gizdavic-Nikolaidis ◽  
Michel K. Nieuwoudt ◽  
Simon Swift
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Atp Synthase ◽  
Acid Stress ◽  
Reactive Oxygen ◽  
Antimicrobial Action ◽  
Oxygen Species ◽  
E Coli ◽  
Production Of Hydrogen

Polyaniline (PANI) and functionalised polyanilines (fPANI) are novel antimicrobial agents whose mechanism of action was investigated.Escherichia colisingle gene deletion mutants revealed that the antimicrobial mechanism of PANI likely involves production of hydrogen peroxide while homopolymer poly(3-aminobenzoic acid), P3ABA, used as an example of a fPANI, disrupts metabolic and respiratory machinery, by targeting ATP synthase and causes acid stress. PANI was more active againstE. coliin aerobic, compared to anaerobic, conditions, while this was apparent for P3ABA only in rich media. Greater activity in aerobic conditions suggests involvement of reactive oxygen species. P3ABA treatment causes an increase in intracellular free iron, which is linked to perturbation of metabolic enzymes and could promote reactive oxygen species production. Addition of exogenous catalase protectedE. colifrom PANI antimicrobial action; however, this was not apparent for P3ABA treated cells. The results presented suggest that PANI induces production of hydrogen peroxide, which can promote formation of hydroxyl radicals causing biomolecule damage and potentially cell death. P3ABA is thought to act as an uncoupler by targeting ATP synthase resulting in a futile cycle, which precipitates dysregulation of iron homeostasis, oxidative stress, acid stress, and potentially the fatal loss of proton motive force.

scholarly journals Does the Interference of GR® Volunteer Corn Alters Stress Metabolism on Soybean?

2018 ◽  
Vol 36 (0) ◽  
Author(s):  
C. PIASECKI ◽  
M.A. RIZZARDI ◽  
J. SCHONS ◽  
A. CAVERZAN ◽  
G. CHAVARRIA
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Oxygen Species ◽  
Yield Losses ◽  
Soybean Yield ◽  
H2o2 Content ◽  
The Mean ◽  
Volunteer Corn ◽  
Corn Plants

ABSTRACT: The cultivation of GR® corn prior to soybean favors the occurrence of GR® volunteer corn plants interfering in soybean crops. The interference of volunteer corn causes the soybean yield losses, and the magnitude of losses varies with the corn density. The soybean yield losses can be partially explained by the occurrence of oxidative stress, which occurs by the higher content of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2). The objective of this study was to quantify H2O2 content and the activity of superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) on soybean as a function of interference of populations of GR® volunteer corn originated from individual plants and clumps (clumps are seven corn plants emerged at the same point) in different times, as well as to determine wheter this interference alters stress metabolism on soybean. Quantification was performed at 20, 35 and 46 days after emergence (DAE) of soybean. The mean volunteer corn populations were 0, 0.5, 1, 2, 4, 8, 10 and 12 plants or clumps m-2. The results show changes in H2O2 content and SOD, CAT and APX activity as a response to interference with volunteer corn populations and origins. The higher activity was observated for SOD. Soybean yield reduce with the increase of populations of volunteer corn originated from individual plants and clumps.

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