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Signalling Pathways in The Regulation of Cellular Responses to Exercise
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Anders Gudiksen, Stine Ringholm, Henriette Pilegaard
Exercise has been shown to increase global glutathionylation and carbonylation in rat SkM (36), supporting the finding that a single exercise bout elicits oxidation of proteins. In accordance, the effects of ROS signalling on gene transcription have been suggested to be executed through post-translational modifications and localization of transcription factors such as NFkB and Nrf2 (3, 36, 37, 109, 122). Calcineurin has been shown to be susceptible to oxidation, which disrupts enzyme activation, indicating that also phosphatases in SkM are redox sensitive (12). In addition, endogenously produced ROS has been reported to target numerous redox active cysteine residues in proteins via S-glutathionylation (protein-SSG), disulfide bond formation (S-S), and S-nitrosation (protein-SNO) post-translational modifications indicating ROS-dependent regulation of enzyme activity (20). Together this provides evidence that ROS signalling involves multiple post-translational modifications of proteins. However, the potential ROS-mediated regulation of redox-sensitive cysteine residues in selected proteins in response to exercise would be very interesting to pursue in future studies.
Pharmacologic Ascorbate Influences Multiple Cellular Pathways Preferentially in Cancer Cells
Published in Qi Chen, Margreet C.M. Vissers, Cancer and Vitamin C, 2020
Qi Chen, Kishore Polireddy, Ping Chen, Ramesh Balusu, Tao Wang, Ruochen Dong
The ascorbate-induced loss of GAPDH activity has two possible explanations. First, GAPDH activity is directly influenced by NAD+ levels. Second, ascorbate may oxidize the GAPDH active site (cysteine 152, C152) and lower GAPDH activity. Interestingly, a previous study showed that the C152 of GAPDH was only reversibly affected by pharmacologic ascorbate and underwent S-glutathionylation. The irreversibly oxidized form, Cys-SO3H, which meant to reduce GAPDH activity, was not detected [5]. Glutathionylation effects on protein activity are not completely known, but one of its roles is that it protects the cysteine amino acids from becoming further oxidized. These data indicate the oxidation at the active site of GAPDH may not be the mechanism. Meanwhile, as supplementation of NAD+ prevents ascorbate-induced ATP loss in cancer cells, it is more likely that the loss of GAPDH activity in ascorbate-treated cells is due to the loss of NAD+.
The Glutathione Redox State and Zinc Mobilization from Metallothionein and Other Proteins with Zinc–Sulfur Coordination Sites
Published in Christopher A. Shaw, Glutathione in the Nervous System, 2018
Most glutathione research has focused on the functions of GSH, and very little is known about possible functions of GSSG. In fact, it would be rather surprising if the only purpose of glutathione reductase and peroxidase were the control of the GSH–GSSG redox state and if GSSG were not utilized in any other way. Chemically, the possibility that GSSG has special functions is an attractive hypothesis, because GSSG is an electrophile and a mild oxidizing agent, in contrast to GSH, which is a nucleophile and a reducing agent. Aside from an interaction between MT and GSSG (see section 4) and glutathionylation (S-thiolation) of proteins under conditions of oxidative stress (Thomas, Poland, and Honzatko 1995), specific molecular actions involving GSSG have apparently not been reported. The remaining discussion, therefore, addresses changes of the GSH–GSSG redox state without specifying the precise nature of the underlying chemistry.
The level of S-glutathionylated protein is a predictor for metastasis in colorectal cancer and correlated with those of Nrf2/Keap1 pathway
Published in Biomarkers, 2021
Liang-Che Chang, Chung-Wei Fan, Wen-Ko Tseng, Chung-Ching Hua
S-glutathionylation patterns of proteins are altered in diseases caused by redox deregulation including cancer (Grek et al.2013) and linked to redox signals originating from mitochondria (Mailloux and Treberg 2016), whose functions are important for tumorigenesis (Weinberg and Chandel 2015). The functions of redox-sensitive signalling transduction molecules and the activities of transcription factors related to the initiation and development of CRC (colorectal cancer) can be modified by S-glutathionylation (Liu et al.2017). Protein S-glutathionylation can be proceeded non-enzymatically by GSSG (glutathione disulphide) spontaneously or by GSH (glutathione) under oxidative or nitrosative stress, and protects proteins from proteolysis and modifies their functions (Zhang et al.2018).
Human carbonic anhydrases and post-translational modifications: a hidden world possibly affecting protein properties and functions
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Anna Di Fiore, Claudiu T. Supuran, Andrea Scaloni, Giuseppina De Simone
Exposure to reactive oxygen or nitrogen species is often related to disease conditions associated with redox imbalance. This condition can determine reversible oxidation of cysteine residues in target proteins, which can further proceed to an irreversible molecular damage. This undesired process can be mitigated by S-glutathionylation, a specific PTM at protein cysteines that involves the reversible addition of the tripeptide glutathione (GSH), the most abundant low-molecular-mass thiol within most cell types63,64. A number of findings supports an essential role of S-glutathionylation in modulating protein function and in regulating cellular signalling pathways associated with viral infection, tumour-induced apoptosis and other pathophysiological processes.
The new H2S-releasing compound ACS94 exerts protective effects through the modulation of thiol homoeostasis
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Daniela Giustarini, Valerio Tazzari, Ivan Bassanini, Ranieri Rossi, Anna Sparatore
GSH plays a protective role in relation to cellular oxidative damage, which mostly occurs during inflammation. If the oxidative stress is severe, glutathione disulphide (GSSG) may accumulate, leading to protein S-glutathionylation, with the activation/inactivation of several regulatory pathways32. A GSH decrease can also occur through irreversible conjugation with electrophilic species and the formation of chemically stable sulphides of GSH, which are further metabolised and excreted after the removal of glycine and glutamic acid and the acetylation of the cysteinyl amino group to form mercapturic acid33.