Progress in the research of GSH in cells

Abstract

Glutathione (GSH), γ-Glu-Cys-Gly, is one of the most abundant small non-protein thiol molecules in mammalian tissues, particularly in the liver. Although glutathione is present in thiol-reduced (GSH) and disulfide oxidized (GSSG) forms, the predominant form is GSH and its content can exceed 10 mmol/L in liver cells. As an important intracellular reductant, GSH has many biological functions in cells. Its major function is as an anti-oxidant as it can protect proteins from oxidation by reversible posttranslational modification (glutathionylation) and decrease reactive oxygen species-mediated damage. However, it does have numerous other functions, including to chelate metal irons; enhance the absorption of iron, selenium and calcium; participate in lipid and insulin metabolism; regulate cellular events such as gene expression, DNA and protein synthesis, cell proliferation and apoptosis, redox-dependent signal transduction pathways, cytokine production and the immune response; and control protein glutathionylation. Therefore, GSH plays important roles in cell survival and health, and an imbalance in the GSH level can lead to many diseases. In this review, we provide an overview of the function of GSH in mammalian cells and discuss future research of GSH. Glutathione (GSH) is the most abundant intracellular nonprotein thiol, and was first identified by Hopkins [1] and Kendall [2]. About 85%-90% GSH is freely distributed in the cytosol, but it is also present in organelles including the mitochondria, peroxisomes, nuclear matrix and endoplasmic reticulum (ER). It is mainly produced in cells to help protect against oxidative stress. It is well known that peroxides are highly unstable and readily form very damaging free radicals upon decomposition, and these radical groups are the main source of oxidative stress. As an important reductant, GSH can scavenge these free radicals using the thiol bridge (i.e., via the sulfhydryl [-SH] groups), which generates water and yields the oxidized form of glutathione (GSSG). Via the reducing power of its free sulfhydryl (-SH), GSH plays a key role in many cellular processes. For example, Pan and Berk's research group [3] has shown that glutathionylation regulates TNF-α-induced capase-3 cleavage and apoptosis, and that capase-3 glutathionylation attenuates caspase-3 cleavage and inhibits endothelial cell death. This research group also showed that protein glutathionylation can regulate the cell death pathway [3]. Because GSH can also detoxify metal irons and ROS, it can participate in protein and DNA synthesis, and affect cell proliferation. In the following review, we will describe the characteristics, functions and future prospects for GSH.

Oxidative Stress in Autism Spectrum Disorder—Current Progress of Mechanisms and Biomarkers

“…They can cause oxidative stress, which can lead to ASD ( 4 , 149 ). In this case, it will expend a significant amount of GSH ( 150 , 151 ). This may be one of the reasons for the disparities in the results of different studies.…”

Degradation and antioxidant activities of peptides and zinc–peptide complexes during in vitro gastrointestinal digestion

“…In this study, two of these metal-chelating peptides, which have high Zn chelating and antioxidant properties, i.e., Ser-Met (SM) and Asn-Cys-Ser (NCS), were used as models for investigating the degradation of peptide ligands and their zinc complexes in the gastrointestinal tract. Reduced glutathione (GSH) constitutes another zinc ligand with powerful antioxidant and metal chelating properties (Zhao, Ruan, & Li, 2011). Therefore, the objective of this study were to (a) investigate the resistance of peptides and Zn-peptide complexes to in vitro digestion conditions and (b) evaluate whether the coordination of Zn affects the resistance of these peptides to enzymatic hydrolysis.…”

Regulation of Antioxidant Stress-Responsive Transcription Factor Nrf2 Target Gene in the Reduction of Radiation Damage by the Thrombocytopenia Drug Romiplostim

“…22,23) GCL is the rate-limiting enzyme responsible for the synthesis pathway of glutathione, which is the most important intracellular anti-oxidant. 24,25) When oxidative stress occurs in the living body, the transcriptional activity of the Gclc gene increases due to glutathione synthesis, which acts as a defense mechanism. 26) The effect of RP on dysfunction was suggested to consequently affect the Nrf2 redox system and contribute to its target gene expression.…”