The redox switch that regulates molecular chaperones

2015 ◽  
Vol 6 (4) ◽  
pp. 269-284 ◽  
Author(s):  
Myra E. Conway ◽  
Christopher Lee
Keyword(s):  
Redox Regulation ◽  
Structural Rearrangement ◽  
Antioxidant Systems ◽  
Cysteine Oxidation ◽  
Hydrophobic Region ◽  
Physiological Importance ◽  
Redox Active ◽  
Polypeptide Folding ◽  
Integral Role ◽  
The Impact

AbstractModification of reactive cysteine residues plays an integral role in redox-regulated reactions. Oxidation of thiolate anions to sulphenic acid can result in disulphide bond formation, or overoxidation to sulphonic acid, representing reversible and irreversible endpoints of cysteine oxidation, respectively. The antioxidant systems of the cell, including the thioredoxin and glutaredoxin systems, aim to prevent these higher and irreversible oxidation states. This is important as these redox transitions have numerous roles in regulating the structure/function relationship of proteins. Proteins with redox-active switches as described for peroxiredoxin (Prx) and protein disulphide isomerase (PDI) can undergo dynamic structural rearrangement resulting in a gain of function. For Prx, transition from cysteine sulphenic acid to sulphinic acid is described as an adaptive response during increased cellular stress causing Prx to form higher molecular weight aggregates, switching its role from antioxidant to molecular chaperone. Evidence in support of PDI as a redox-regulated chaperone is also gaining impetus, where oxidation of the redox-active CXXC regions causes a structural change, exposing its hydrophobic region, facilitating polypeptide folding. In this review, we will focus on these two chaperones that are directly regulated through thiol-disulphide exchange and detail how these redox-induced switches allow for dual activity. Moreover, we will introduce a new role for a metabolic protein, the branched-chain aminotransferase, and discuss how it shares common mechanistic features with these well-documented chaperones. Together, the physiological importance of the redox regulation of these proteins under pathological conditions such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis will be discussed to illustrate the impact and importance of correct folding and chaperone-mediated activity.

Confocal and SEM imaging to demonstrate food pathogen- biofilm biocontrol by pyocyanin from Pseudomonas aeruginosa BTRY1

2016 ◽  
Vol 6 (01) ◽  
pp. 5218
Author(s):  
Laxmi Mohandas ◽  
Anju T. R. ◽  
Sarita G. Bhat*
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Antibiofilm Activity ◽  
Opportunistic Pathogens ◽  
Redox Active ◽  
Sem Imaging ◽  
The Impact

An assortment of redox-active phenazine compounds like pyocyanin with their characteristic blue-green colour are synthesized by Pseudomonas aeruginosa, Gram-negative opportunistic pathogens, which are also considered one of the most commercially valuable microorganisms. In this study, pyocyanin from Pseudomonas aeruginosa BTRY1 from food sample was assessed for its antibiofilm activity by micro titer plate assay against strong biofilm producers belonging to the genera Bacillus, Staphylococcus, Brevibacterium and Micrococcus. Pyocyanin inhibited biofilm activity in very minute concentrations. This was also confirmed by Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM). Both SEM and CLSM helped to visualize the biocontrol of biofilm formation by eight pathogens. The imaging and quantification by CLSM also established the impact of pyocyanin on biofilm-biocontrol mainly in the food industry.

scholarly journals Exploring the Impact of Technology-Facilitated Abuse and Its Relationship with Domestic Violence: A Qualitative Study on Experts’ Perceptions

2021 ◽  
Vol 8 ◽  
pp. 233339362110281
Author(s):  
Renee Fiolet ◽  
Cynthia Brown ◽  
Molly Wellington ◽  
Karen Bentley ◽  
Kelsey Hegarty
Keyword(s):  
Domestic Violence ◽  
Service Providers ◽  
Structured Interviews ◽  
Specialist Service ◽  
Data Coding ◽  
Integral Role ◽  
Impact Of Technology ◽  
The Impact ◽  
The Relationship ◽  
Inductive Thematic Analysis

Technology-facilitated abuse can be a serious form of domestic violence. Little is known about the relationship between technology-facilitated abuse and other types of domestic violence, or the impact technology-facilitated abuse has on survivors. The aim of this interpretative descriptive study is to understand domestic violence specialist service providers’ perspectives on the impact of technology-facilitated abuse, and the link between technology-facilitated abuse and other forms of domestic violence. A qualitative approach using 15 semi-structured interviews were undertaken with Australian domestic violence specialist practitioners, and three themes were identified through data coding using inductive thematic analysis. Another form of control describes technology-facilitated abuse behaviors as enacting controlling behaviors using new mediums. Amplifies level of fear characterizes the impact of technology-facilitated abuse. A powerful tool to engage others describes opportunities technology offers perpetrators to abuse through engaging others. Findings highlight technology-facilitated abuse’s complexity and integral role in domestic violence and can assist clinicians to understand the impact and harm that can result from technology-facilitated abuse.

Caracole as a Potential Neuroprotective Agent for Neurological Diseases: A Systematic

2021 ◽  
Vol 20 ◽  
Author(s):  
Mohammad Zamanian ◽  
Małgorzata Kujawska ◽  
Marjan Nikbakht Zadeh ◽  
Amin Hassanshahi ◽  
Soudeh Ramezanpour ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Parkinson's Disease ◽  
Brain Injury ◽  
Neurological Diseases ◽  
Antioxidant Systems ◽  
Neuroprotective Agent ◽  
The Impact

Background & objective: Neurological diseases are becoming a significant problem worldwide, with the elderly at a higher risk of being affected. Several researchers have investigated the neuroprotective effects of Carvacrol (CAR) (5-isopropyl-2-methyl phenol). This review systematically surveys the existing literature on the impact of CAR when used as a neuroprotective agent in neurological diseases. Methods: The systematic review involved English articles published in the last ten years obtained from PubMed, Google Scholar, and Scopus databases. The following descriptors were used to search the literature: “Carvacrol” [Title] AND “neuroprotective (neuroprotection)” [Title] OR “stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, seizure, epilepsy [Title]. Results: : A total of 208 articles were retrieved during the search process, but only 20 studies met the eligibility criteria and were included for review. A total of 20 articles were identified, in which the efficacy of CAR was described in experimental models of stroke, traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, , epilepsy, and seizure, through motor deficits improvements in neurochemical activity, especially antioxidant systems, reducing inflammation, oxidative stress and apoptosis as well as inhibition of TRPC1 and TRPM7. Conclusion : The data presented in this study support the beneficial impact of CAR on behavioural and neurochemical deficits. CAR benefits accrue because of its anti-apoptotic, antioxidant, and anti-inflammatory properties. Therefore, CAR has emerged as an alternative treatment for neurological disorders based on its properties.

scholarly journals Influence of Capital Structure on Corporate Performance of Listed Firm in PSX: Role of External Factors

2021 ◽  
Vol 7 (3) ◽  
Author(s):  
Abdul Hameed ◽  
Farheen Zahra Hussain ◽  
Khawar Naheed ◽  
Muhammad Sadiq Shahid
Keyword(s):  
Firm Performance ◽  
Capital Structure ◽  
Debt Financing ◽  
External Factors ◽  
Least Square ◽  
Total Debt ◽  
Integral Role ◽  
Equity Ratio ◽  
The Impact

Purpose: A company’s capital structure is a blend of its equity and debt financing and is considered a significant factor in the valuation of any firm. The decisions related to capital structure formation play an integral role for the firms, therefore; this research tends to explore the factors of capital structure and their impact on firm performance. For this purpose, financial data for different listed companies in PSX has been gathered, and dividends and taxes are used as firm external factors.  Design/Methodology/Approach: To examine the impact, the panel data has been used for the period 2016-2020 and panel least square has been applied. Findings: The findings suggest that among the variables current ratio, dividends, taxation, total debt to total equity ratio, and the firm size are statistically significant to profitability. The study also concludes that dividends and tax have a greater impact on capital structure and firm performance.   Implications/Originality/Value: Managers and owners of the firms must make sure that their profits are used for future investments rather than payment of debts to avoid bankruptcy.  

scholarly journals Proteome-Wide Survey Reveals Norbornene Is Complementary to Dimedone and Related Nucleophilic Probes for Cysteine Sulfenic Acid

2019 ◽  
Author(s):  
Lisa Alcock ◽  
Maike Langini ◽  
Kai Stühler ◽  
Marc Remke ◽  
Michael Perkins ◽  
...  
Keyword(s):  
Redox Regulation ◽  
Chemical Reactivity ◽  
Live Cells ◽  
Chemical Probes ◽  
Cysteine Oxidation ◽  
Sulfenic Acid ◽  
Proteomics Analysis ◽  
New Members ◽  
Specific Chemical ◽  
Future Studies

<p>Detection of cysteine sulfenic acid in live cells is critical in advancing our understanding of cysteine redox chemistry and its biological function. Accordingly, there is a need to develop sulfenic acid-specific chemical probes with distinct reaction mechanisms to facilitate proteome-wide detection of this important posttranslational modification. Herein, we report the first whole-cell proteomics analysis using a norbornene probe to detect cysteine sulfenic acid in live HeLa cells. Comparison of the enriched proteins to those identified using dimedone and other <i>C</i>-nucleophilic probes revealed a complementary reactivity profile. Remarkably, 148 new members of the sulfenome were identified. These discoveries highlight how subtle differences in chemical reactivity of both the probes and cysteine residues influence detection. Overall, this study expands our understanding of protein oxidation at cysteine and reveals new proteins to consider for future studies of cysteine oxidation, redox regulation and signaling, and the biochemistry of oxidative stress. </p>

scholarly journals Proteome-Wide Survey Reveals Norbornene Is Complementary to Dimedone and Related Nucleophilic Probes for Cysteine Sulfenic Acid

2019 ◽  
Author(s):  
Lisa Alcock ◽  
Maike Langini ◽  
Kai Stühler ◽  
Marc Remke ◽  
Michael Perkins ◽  
...  
Keyword(s):  
Redox Regulation ◽  
Chemical Reactivity ◽  
Live Cells ◽  
Chemical Probes ◽  
Cysteine Oxidation ◽  
Sulfenic Acid ◽  
Proteomics Analysis ◽  
New Members ◽  
Specific Chemical ◽  
Future Studies

<p>Detection of cysteine sulfenic acid in live cells is critical in advancing our understanding of cysteine redox chemistry and its biological function. Accordingly, there is a need to develop sulfenic acid-specific chemical probes with distinct reaction mechanisms to facilitate proteome-wide detection of this important posttranslational modification. Herein, we report the first whole-cell proteomics analysis using a norbornene probe to detect cysteine sulfenic acid in live HeLa cells. Comparison of the enriched proteins to those identified using dimedone and other <i>C</i>-nucleophilic probes revealed a complementary reactivity profile. Remarkably, 148 new members of the sulfenome were identified. These discoveries highlight how subtle differences in chemical reactivity of both the probes and cysteine residues influence detection. Overall, this study expands our understanding of protein oxidation at cysteine and reveals new proteins to consider for future studies of cysteine oxidation, redox regulation and signaling, and the biochemistry of oxidative stress. </p>

scholarly journals Links between exercise/nutrition and antioxidants - protective effects on immune/respiratory systems as defense against viral infections

2020 ◽  
Vol 8 (36) ◽  
pp. 23-31
Author(s):  
Abdurrahman Kharbat ◽  
Stephen Rossettie ◽  
Mimi Zumwalt
Keyword(s):  
Viral Infections ◽  
Viral Disease ◽  
Antioxidant Systems ◽  
Protective Effects ◽  
Enzymatic Antioxidant ◽  
Optimal Dosing ◽  
Open Window ◽  
The Impact ◽  
The Relationship ◽  
Harmful Effects

This paper discusses factors involved in COVID-19 pathophysiology, with a focus on nutrition, exercise, enzymatic antioxidant systems, and the interplay between immune tolerance and resistance. Of all the supplements, zinc has the most evidence for effectiveness against viruses. However, these data were based primarily on studies measuring duration of the common cold rather than on COVID-19, and optimal dosing remains unclear. Exercise has been shown to have protective tolerogenic effects against viral infection due to the impact of extracellular superoxide dismutases (EC-SODs). Exercise may have a combination of beneficial and harmful effects on outright resistance to viruses in the short term, but taken as a whole it likely has a net protective effect on the immune system. The evidence is examined through the lens of the open window theory and a thorough investigation of the relationship between EC-SODs and exercise/diet. By better understanding the host-virus relationship, clinicians and researchers alike can collaborate to establish guiding principles regarding the steps that individuals can take to protect against some of the deleterious effects of viral infections. More research in this area is needed to understand the relationships among exercise, nutrition, and viral disease. Keywords: COVID-19, SARS CoV-2, nutrition, zinc, EC-SODs, superoxide dismutase, exercise, enzymatic antioxidant/immune systems

Mycotoxin Deactivator Improves Performance, Antioxidant Status, and Reduces Oxidative Stress in Nursery Pigs Fed Diets Containing Mycotoxins

2021 ◽  
Author(s):  
Erika Vivian Santos ◽  
Dalton Oliveira Fontes ◽  
Mara da Silveira Benfato ◽  
Fernanda Schäfer Hackenharr ◽  
Tiago Salomon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Status ◽  
Control Diet ◽  
Negative Control ◽  
Antioxidant Systems ◽  
Contamination Level ◽  
Standard Diet ◽  
Nursery Pigs ◽  
Inclusion Rate ◽  
The Impact

Abstract Ingestion of mycotoxins can result in many problems, including decreased growth rates and immune suppression. The present study aimed to evaluate the impact of the supplementation of a mycotoxin deactivator composed by adsorbent clay minerals, inactivated fermentation extracts of Saccharomyces cerevisiae, blend of antioxidants, organic acids and botanicals in diets containing added mycotoxins for nursery pigs on their performance and antioxidant status. Ninety pigs weaned with 24 days of age (7.12 ± 0.68 kg of BW) were used. Pigs were housed in pens of 3 animals each according to body weight, litter origin and sex. The dietary treatments consisted of feeding the pigs with: a standard control diet as negative control (NC; mycotoxin levels at accepted regulatory Brazilian Ministry of Agriculture standards Deoxynivalenol (DON): &lt;100 ug/ kg; Zearalenone (ZEA): &lt;20 ug/ kg Fumonisins (FB): &lt;1 mg/ kg); the standard diet added with mycotoxins to reach a low contamination level considered as positive low (PCL-; DON: 900 ug/ kg; ZEA: 100 ug/ kg; FB: 5,000 ug/ kg) without deactivator; a positive low added the deactivator at an inclusion rate of 1 kg/ ton (PCL+); the standard diet added with mycotoxins to reach a high contamination level considered as positive high (PCH-; DON: 4,500 ug/ kg; ZEA: 500 ug/ kg; FB: 18,000 ug/ kg) without the deactivator; and a positive high added the deactivator at an inclusion rate of 5 kg/ ton (PCH+). Pigs were individually weighed at the beginning and at the end of each phase and feed intake recorded based on daily pen intake during the experiment. On d 7, 19, 34 and 43 post-weaning blood samples were drawn for antioxidant analyses. Antioxidant enzymes (glutathione peroxidase (GPx) and total superoxide dismutase (TSOD)), vitamins (Vit A, E, and C), and malondialdehyde (MDA)) were evaluated in erythrocyte and plasma samples. Pigs challenged with mycotoxins presented lower performance traits, decrease in the efficiency of central antioxidant systems (↓GPx, ↓TSOD, ↓Vit A, ↓Vit E and ↓Vit C) and a higher oxidative damage to lipids (↑MDA) when compared to the control and deactivator associated treatments. Our findings showed that the use of a mycotoxin deactivator can mitigate the negative impacts on performance and oxidative stress when animals are subjected to diets contaminated by different levels of mycotoxins.

Pinpointing cysteine oxidation sites by high-resolution proteomics reveals a mechanism of redox-dependent inhibition of human STING

2021 ◽  
Vol 14 (680) ◽  
pp. eaaw4673
Author(s):  
Natalia Zamorano Cuervo ◽  
Audray Fortin ◽  
Elise Caron ◽  
Stéfany Chartier ◽  
Nathalie Grandvaux
Keyword(s):  
Posttranslational Modifications ◽  
Protein Function ◽  
Disulfide Bonds ◽  
Redox Regulation ◽  
Mass Spectrometry Analysis ◽  
Type I ◽  
Cysteine Oxidation ◽  
Spectrometry Analysis ◽  
Host Interactions ◽  
In Cells

Protein function is regulated by posttranslational modifications (PTMs), among which reversible oxidation of cysteine residues has emerged as a key regulatory mechanism of cellular responses. Given the redox regulation of virus-host interactions, the identification of oxidized cysteine sites in cells is essential to understand the underlying mechanisms involved. Here, we present a proteome-wide identification of reversibly oxidized cysteine sites in oxidant-treated cells using a maleimide-based bioswitch method coupled to mass spectrometry analysis. We identified 2720 unique oxidized cysteine sites within 1473 proteins with distinct abundances, locations, and functions. Oxidized cysteine sites were found in numerous signaling pathways, many relevant to virus-host interactions. We focused on the oxidation of STING, the central adaptor of the innate immune type I interferon pathway, which is stimulated in response to the detection of cytosolic DNA by cGAS. We demonstrated the reversible oxidation of Cys148 and Cys206 of STING in cells. Molecular analyses led us to establish a model in which Cys148 oxidation is constitutive, whereas Cys206 oxidation is inducible by oxidative stress or by the natural ligand of STING, 2′3′-cGAMP. Our data suggest that the oxidation of Cys206 prevented hyperactivation of STING by causing a conformational change associated with the formation of inactive polymers containing intermolecular disulfide bonds. This finding should aid the design of therapies targeting STING that are relevant to autoinflammatory disorders, immunotherapies, and vaccines.

scholarly journals Impact of key residues within chloroplast thioredoxin-f on recognition for reduction and oxidation of target proteins

2019 ◽  
Vol 294 (46) ◽  
pp. 17437-17450 ◽  
Author(s):  
Yuichi Yokochi ◽  
Kazunori Sugiura ◽  
Kazuhiro Takemura ◽  
Keisuke Yoshida ◽  
Satoshi Hara ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Redox Regulation ◽  
Target Recognition ◽  
Dynamics Simulation ◽  
Target Proteins ◽  
Specific Target ◽  
Redox Responsive ◽  
Key Residues ◽  
Protein Reduction ◽  
The Impact

Thioredoxin (Trx) is a redox-responsive protein that modulates the activities of its target proteins mostly by reducing their disulfide bonds. In chloroplasts, five Trx isoforms (Trx-f, Trx-m, Trx-x, Trx-y, and Trx-z) regulate various photosynthesis-related enzymes with distinct target selectivity. To elucidate the determinants of the target selectivity of each Trx isoform, here we investigated the residues responsible for target recognition by Trx-f, the most well-studied chloroplast-resident Trx. As reported previously, we found that positively-charged residues on the Trx-f surface are involved in the interactions with its targets. Moreover, several residues that are specifically conserved in Trx-f (e.g. Cys-126 and Thr-158) were also involved in interactions with target proteins. The validity of these residues was examined by the molecular dynamics simulation. In addition, we validated the impact of these key residues on target protein reduction by studying (i) Trx-m variants into which we introduced the key residues for Trx-f and (ii) Trx-like proteins, named atypical Cys His-rich Trx 1 (ACHT1) and ACHT2a, that also contain these key residues. These artificial or natural protein variants could reduce Trx-f–specific targets, indicating that the key residues for Trx-f are critical for Trx-f–specific target recognition. Furthermore, we demonstrate that ACHT1 and ACHT2a efficiently oxidize some Trx-f–specific targets, suggesting that its target selectivity also contributes to the oxidative regulation process. Our results reveal the key residues for Trx-f–specific target recognition and uncover ACHT1 and ACHT2a as oxidation factors of their target proteins, providing critical insight into redox regulation of photosynthesis.

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