Imbalanced GSH/ROS and sequential cell death

Abstract

Reactive oxygen species (ROS) are produced in cells during metabolic processes.Excessive intracellular ROS may react with large biomolecules, such as DNA, RNA, proteins, and small biomolecules, that is, glutathione (GSH) and unsaturated fatty acids. GSH has physiological functions, including free radical scavenging, antioxidation, and electrophile elimination. The disruption of ROS/GSH balance results in the deleterious oxidation and chemical modification of biomacromolecules, which eventually leads to cell-cycle arrest and proliferation inhibition, and even induces cell death. Imbalanced ROS/GSH may result from a direct increase of ROS, consumption of GSH, intracellular oxidoreductase interference, or thioredoxin activity reduction. Some chemicals including arsenic trioxide (ATO), pyrogallol (PG), and carbobenzoxy-Leu-Leu-leucinal (MG132) could also disrupt the balance of GSH and ROS. This article reviews the occurrence and consequences of the imbalance between GSH and ROS and introduces factors responsible for the disruption of cellular ROS and GSH balance, resulting in cell death. "GSH" and "ROS" were used as keywords to search the relevant literaturess.

Metabolic plasticity of serine metabolism is crucial for cGAS/STING-signalling and innate immune response to viral infections in the gut

“…2G). The primordial function of GSH is to counterbalance free radicals derived from ROS by being oxidized to glutathione disulphide (GSSG) (34, 35) (Fig. S2H).…”

“…2J). As GSH is also utilized to counterbalance ROS-dependent lipid peroxidation (LPO) (34,35,37,38), we further assessed LPO levels, which were also significantly increased in i Xbp1 cells and further increased upon acute TM treatment (Fig. 2K).…”

Effect of taxifolin on cyclophosphamide-induced oxidative and inflammatory bladder injury in rats

“…tGSH is an endogenous antioxidant with ROS scavenging ability. Disruption of the ROS/GSH balance results in the oxidation of biomacromolecules; this leads to cell cycle arrest and even cell death [26].…”

Identification and validation of ferroptosis-related lncRNA signatures as a novel prognostic model for glioma

“…Among these pathways, EMT can not only enhance tumor invasiveness but also be associated with enhanced stem cell properties and drug resistance ( Aiello and Kang 2019 ). Angiogenesis-related pathways and glutathione metabolism are also enriched; angiogenesis (the formation of new blood vessels) has been shown to be an integral part of cancer development ( Viallard and Larrivée 2017 ), and glutathione is an important component against reactive oxygen species (ROS), which are key substances in the ferroptosis process ( Liu et al, 2022 ). Interestingly, many immune-related pathways were also enriched, including primary immunodeficiency, IL6-JAK-STAT3 signaling and the IL2-STAT5 pathway.…”