The glutathione system and the related thiol network in Caenorhabditis elegans

Abstract

Advances in the field of redox biology have contributed to the understanding of the complexity of the thiol-based system in mediating signal transduction. The redox environment is the overall spatiotemporal balance of oxidation-reduction systems within the integrated compartments of the cell, tissues and whole organisms. The ratio of the reduced to disulfide glutathione redox couple (GSH:GSSG) is a key indicator of the redox environment and its associated cellular health. The reaction mechanisms of glutathione-dependent and related thiol-based enzymes play a fundamental role in the function of GSH as a redox regulator. Glutathione homeostasis is maintained by the balance of GSH synthesis (de novo and salvage pathways) and its utilization through its detoxification, thiol signalling, and antioxidant defence functions via GSH-dependent enzymes and free radical scavenging. As such, GSH acts in concert with the entire redox network to maintain reducing conditions in the cell. Caenorhabditis elegans offers a simple model to facilitate further understanding at the multicellular level of the physiological functions of GSH and the GSH-dependent redox network. This review discusses the C. elegans studies that have investigated glutathione and related systems of the redox network including; orthologs to the protein-encoding genes of GSH synthesis; glutathione peroxidases; glutathione-S-transferases; and the glutaredoxin, thioredoxin and peroxiredoxin systems.

Caenorhabditis elegans as a Model Organism to Evaluate the Antioxidant Effects of Phytochemicals

“…Under normal physiological conditions most of the redox-active glutathione molecules are in the reduced form (GSH) and only a minor fraction is present as glutathione disulfide (GSSG). The GSH/GSSG couple contributes to the maintenance of the reduced intracellular milieu [ 72 ] and can be used as an indicator of the redox status in C. elegans [ 73 ]. In its reduced form, glutathione can directly reduce substrates, but it also acts indirectly through the glutaredoxin system and intervenes in detoxification and repair processes in combination with glutathione S -transferase [ 74 ].…”

“…The activation of these pathways promotes, among others, the expression of catalase ( ctl-1 ), superoxide dismutase-3 ( sod-3 ), metallothionein ( mtl-1 ), heat shock proteins ( hsp ), glutathione S -transferase ( gst-4 ), glutathione peroxidase ( gpx ), γ-glutamylcysteine synthetase ( gcs-1 ), glutathione synthetase ( gss-1 ), glutathione reductase ( gsr-1 ), NAD(P)H:quinone oxidoreductase (NQO-1), or bacterial pathogen defense genes ( lys-7, spp-1 ). All these types of mutants have been used by different authors to evaluate the antioxidant effects and molecular mechanisms of action of multiple phytochemicals, including polyphenols [ 43 , 44 , 73 , 127 , 128 , 129 ].…”

A GGT Inhibitor Suppresses IL-6 and IL-8 Expressions Enhanced by LPS in Gingival Fibroblasts

“…Glutathione (GSH) has both antioxidant and detoxifying effects. GSH regulates thiol, antioxidant component, redox transitions in cell signaling, contributing to various illnesses (8) . Periodontitis is predominantly due to exaggerated host response to pathogenic microorganisms and their products which causes an imbalance between the reactive oxygen species and antioxidant.…”

An omega‐class glutathione S‐transferase in the brown planthopper Nilaparvata lugens exhibits glutathione transferase and dehydroascorbate reductase activities

“…GSH is known to be a redox regulator. Thiol transferase is involved in GSH homeostasis, which is important for antioxidant defense (Board & Menon, ; Ferguson & Bridge, ). DHA reductase is responsible for maintaining the balance of ascorbate, which functions in scavenging reactive oxygen species (Noshi et al, ; Sofo, Scopa, Nuzzaci, & Vitti, ).…”

“…GSTs exist widely in both prokaryotic and eukaryotic species. Mammalian GSTs containing several classes have been reported: alpha, mu, pi, omega, sigma, theta, and zeta (Ferguson & Bridge, ; Mannervik, Board, Hayes, Listowsky, & Pearson, ), whereas six designated GST classes (delta, epsilon, omega, sigma, theta, and zeta), as well as some unclassified GSTs (Yamamoto & Yamada, ; Yamamoto et al, ), have been found in Bombyx mori , a lepidopteran model insect. GSTs have been investigated on insect species owing to their function in insecticide detoxification (Casida, ; Ketterman, Saisawang, & Wongsantichon, ; Li, Schuler, & Berenbaum, ; Ranson & Hemingway, ; Sawicki, Singh, Mondal, Benes, & Zimniak, ).…”