Glutathione: Role in Oxidative/Nitrosative Stress, Antioxidant Defense, and Treatments

Raj, Sristi; Bhattacharyya, Camelia; Sarkar, Anwita; Chakraborty, Surupa; Sircar, Esha; Dutta, Sreejita; Sengupta, Rajib

doi:10.1002/slct.202100773

Cited by 51 publications

(31 citation statements)

References 220 publications

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“…For this, adaptation mechanisms to tampering down ROS production are of pivotal importance for the safety of the flight crew. In this context, CAT and GSH are components of the antioxidant defense grid, suppressing the formation of free radicals or reactive species in cells [ 45 , 46 , 47 ]. CAT consists of a first-line antioxidant (enzymes), and GSH belongs at the second line of defense (ancillary factors) [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Estimation of Redox Status in Military Pilots during Hypoxic Flight-Simulation Conditions—A Pilot Study

et al. 2022

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At high altitude conditions, the low-pressure atmospheric oxygen reduces the generation of energy, thus inducing a decrease in oxygen availability. As a result, endurance flights evoke imbalance in redox signaling, posing a safety risk for the pilots involved. The aim of the present study was to assess changes in the redox status of military pilots during flight simulation conditions according to their flight hours (experts vs. novice). A total of seven expert pilots and an equal number of novice pilots (trainees) were recruited from the Center for Airforce Medicine of the Greek Military Airforce. Glutathione (GSH) levels, catalase activity (CAT), total antioxidant capacity (TAC), lipid peroxidation through the thiobarbituric acid-reactive substances (TBARS), and protein oxidative damage through the assay of protein carbonyls (PCs) levels were assessed at two time points, once prior to and once immediately post a scheduled flight simulation. In the experienced pilots’ arms, GSH was significantly increased post-flight simulation, with TAC being simultaneously reduced. On the other hand, in the trainees’ arms, CAT and TAC were both increased post-flight. No differences were noted with regard to the TBARS and PCs post-simulation. When the two groups were compared, TAC and PCs were significantly lower in the trainees compared to the experienced pilots. The present study provides useful insight into the physiological redox status adaptations to hypobaric hypoxic flight conditions among pilots. In a further detail, an increase in GSH response post-flight simulation is being evoked in more experienced pilots, indicating an adaptation to the extreme flight conditions, as they battle oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Estimation of Redox Status in Military Pilots during Hypoxic Flight-Simulation Conditions—A Pilot Study

et al. 2022

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“…Glutathione, or ϒ-glutamylcysteinylglycine (GSH), being the most abundant antioxidant in mammalian tissues, is imperative for several roles in the human body, which include cell proliferation, protein folding, regulation of the cell cycle and cell division, repairing DNA damage and participating in replication, redox-dependent cell signaling, reserve form of cysteine, boosting the immunogenic responses, elimination of toxicants, synthesis of eicosanoids, metal homeostasis, and storage and transportation of NO, among several others [ 16 ]. The celebration around GSH is mostly due to its connection with ROS, which not only makes it the most studied antioxidant in the field of redox biochemistry but also establishes it as a linchpin of redox-regulated cellular defenses against stress factors in a biological system, also establishing it as a very strong denitrosylating agent [ 17 , 18 ].…”

Section: Gsh Synthesis and Denitrosylationmentioning

confidence: 99%

“…The later steps of the pathway are similar for all the studied ways. ϒ-glutamylcysteine, with the help of glutathione synthetases, is reduced to form reduced glutathione (GSH), which is further oxidized (GSSG) depending on the amount of positive or negative feedback generated in the ϒ-glutamyl cycle in the presence of a particular GSH/GSSG ratio in the mammalian system [ 16 , 20 ].…”

Section: Gsh Synthesis and Denitrosylationmentioning

confidence: 99%

S-Denitrosylation: A Crosstalk between Glutathione and Redoxin Systems

et al. 2022

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S-nitrosylation of proteins occurs as a consequence of the derivatization of cysteine thiols with nitric oxide (NO) and is often associated with diseases and protein malfunction. Aberrant S-nitrosylation, in addition to other genetic and epigenetic factors, has gained rapid importance as a prime cause of various metabolic, respiratory, and cardiac disorders, with a major emphasis on cancer and neurodegeneration. The S-nitrosoproteome, a term used to collectively refer to the diverse and dynamic repertoire of S-nitrosylated proteins, is relatively less explored in the field of redox biochemistry, in contrast to other covalently modified versions of the same set of proteins. Advancing research is gradually unveiling the enormous clinical importance of S-nitrosylation in the etiology of diseases and is opening up new avenues of prompt diagnosis that harness this phenomenon. Ever since the discovery of the two robust and highly conserved S-nitrosoglutathione reductase and thioredoxin systems as candidate denitrosylases, years of rampant speculation centered around the identification of specific substrates and other candidate denitrosylases, subcellular localization of both substrates and denitrosylases, the position of susceptible thiols, mechanisms of S-denitrosylation under basal and stimulus-dependent conditions, impact on protein conformation and function, and extrapolating these findings towards the understanding of diseases, aging and the development of novel therapeutic strategies. However, newer insights in the ever-expanding field of redox biology reveal distinct gaps in exploring the crucial crosstalk between the redoxins/major denitrosylase systems. Clarifying the importance of the functional overlap of the glutaredoxin, glutathione, and thioredoxin systems and examining their complementary functions as denitrosylases and antioxidant enzymatic defense systems are essential prerequisites for devising a rationale that could aid in predicting the extent of cell survival under high oxidative/nitrosative stress while taking into account the existence of the alternative and compensatory regulatory mechanisms. This review thus attempts to highlight major gaps in our understanding of the robust cellular redox regulation system, which is upheld by the concerted efforts of various denitrosylases and antioxidants.

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“…Among them, GSH is an important member of the body's endogenous antioxidant. It has the advantages of scavenging free radicals, alleviating damage and maintaining redox equilibrium in cells [27]. When the body is attacked by free radicals, GSH can be used as a direct scavenger of free radicals, a co-substrate of GSH-Px, a cofactor of enzymatic reaction, and a conjugate of many endogenous reactions to improve oxidative stress and delay the development of diabetes [28].…”

Section: Nano-drug Design Based On the Role Of Gsh In Oxidative Stressmentioning

confidence: 99%

Nano-Drug Design Based on the Physiological Properties of Glutathione

2021

Molecules

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Glutathione (GSH) is involved in and regulates important physiological functions of the body as an essential antioxidant. GSH plays an important role in anti-oxidation, detoxification, anti-aging, enhancing immunity and anti-tumor activity. Herein, based on the physiological properties of GSH in different diseases, mainly including the strong reducibility of GSH, high GSH content in tumor cells, and the NADPH depletion when GSSH is reduced to GSH, we extensively report the design principles, effect, and potential problems of various nano-drugs in diabetes, cancer, nervous system diseases, fluorescent probes, imaging, and food. These studies make full use of the physiological and pathological value of GSH and develop excellent design methods of nano-drugs related to GSH, which shows important scientific significance and prominent application value for the related diseases research that GSH participates in or responds to.

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Glutathione: Role in Oxidative/Nitrosative Stress, Antioxidant Defense, and Treatments

Cited by 51 publications

References 220 publications

Estimation of Redox Status in Military Pilots during Hypoxic Flight-Simulation Conditions—A Pilot Study

Estimation of Redox Status in Military Pilots during Hypoxic Flight-Simulation Conditions—A Pilot Study

S-Denitrosylation: A Crosstalk between Glutathione and Redoxin Systems

Nano-Drug Design Based on the Physiological Properties of Glutathione

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