Glutathione – linking cell proliferation to oxidative stress

Abstract

Significance:The multifaceted functions of reduced glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) continue to fascinate plants and animal scientists, not least because of the dynamic relationships between GSH and reactive oxygen species (ROS) that underpin reduction/oxidation (redox) regulation and signalling. Here we consider the respective roles of ROS and GSH in the regulation of plant growth, with a particular focus on regulation of the plant cell cycle. Glutathione is discussed not only as a crucial low molecular weight redox buffer that shields nuclear processes against oxidative challenge but also a flexible regulator of genetic and epigenetic functions. Recent Advances:The intracellular compartmentalization of GSH during the cell cycle is remarkably consistent in plants and animals. Moreover, measurements of in vivo glutathione redox potentials reveal that the cellular environment is much more reducing than predicted from GSH/GSSG ratios measured in tissue extracts. The redox potential of the cytosol and nuclei of non-dividing plant cells is about -300 mV. This relatively low redox potential is maintained even in cells experiencing oxidative stress by a number of mechanisms including vacuolar sequestration of GSSG. We propose that regulated ROS production linked to glutathione-mediated signalling events are the hallmark of viable cells within a changing and challenging environment. Critical Issues:The concept that the cell cycle in animals is subject to redox controls is well established but little is known about how ROS and GSH regulate this process in plants. However, it is increasingly likely that similar redox controls exist in plants, 3 although possibly through different pathways. Moreover, redox-regulated proteins that function in cell cycle checkpoints remain to be identified in plants. While GSHresponsive genes have now been identified, the mechanisms that mediate and regulate protein glutathionylation in plants remain poorly defined.Future Directions: The nuclear GSH pool provides an appropriate redox environment for essential nuclear functions. Future work will function on how this essential thiol interacts with the nuclear thioredoxin system and nitric oxide to regulate genetic and epigenetic mechanisms. The characterization of redox-regulated cell cycle proteins in plants, and the elucidation of mechanisms that facilitate GSH accumulation in the nucleus are keep steps to unravelling the complexities of nuclear redox controls.Diaz 4

A Key Role for Apoplastic H2O2 in Norway Spruce Phenolic Metabolism

“…The cellular redox state has been shown to affect cell proliferation in animals (Diaz-Vivancos et al, 2015), and this is likely also to be the case in plants (Schippers et al, 2016). Differences in redox buffering (i.e.…”

BGP-15 Protects against Oxidative Stress- or Lipopolysaccharide-Induced Mitochondrial Destabilization and Reduces Mitochondrial Production of Reactive Oxygen Species

“…This failure could be explained by the requirement for antioxidants to be present at millimolar concentrations in order to significantly decrease oxidative damage [16]. Furthermore, oxidative stress activates mitogen-activated protein kinase (MAPK) and tyrosine kinase signaling pathways [17,18], nuclear factor-κB (NF-κB), activator protein-1 (AP-1) and hypoxia-inducible factor-1 (HIF-1ɑ) transcription factors, cell cycle proteins [19] and ion channels [20,21]. Therefore, it may be more favorable to prevent those processes, which lead to disease-promoting alterations in the signaling pathways, rather than attempting to reduce ROS levels using antioxidants.…”

Sulfur mustard resistant keratinocytes obtained elevated glutathione levels and other changes in the antioxidative defense mechanism

“…Glutathione (GSH) is considered as the most important cellular defense mechanism against oxidative stress (Diaz-Vivancos et al, 2015). In HaCaT/SM cells was significantly more total glutathione present, throughout.…”