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The role of glutathione and glutathione peroxidase in regulating cellular level of reactive oxygen and nitrogen species.
Microvasc Res. 2020 09; 131:104010.MR

Abstract

Glutathione (GSH) and GSH/glutathione peroxidase (GPX) enzyme system is essential for normal intracellular homeostasis and gets disturbed under pathophysiologic conditions including endothelial dysfunction. Overproduction of reactive oxidative species (ROS) and reactive nitrogen species (RNS) including superoxide (O2•-), and the loss of nitric oxide (NO) bioavailability is a characteristic of endothelial dysfunction. The GSH/GPX system play an important role in eliminating ROS/RNS. Studies have provided important information regarding the interactions of ROS/RNS with the GSH/GPX in biological systems; however, it is not clear how this cross talk affect these reactive species and GSH/GPX enzyme system, under physiologic and oxidative/nitrosative stress conditions. In the present study, we developed a detailed endothelial cell kinetic model to understand the relationship amongst the key enzyme systems including GSH, GPX, peroxiredoxin (Prx) and reactive species, such as hydrogen peroxide (H2O2), peroxynitrite (ONOO-), and dinitrogen trioxide (N2O3). Our simulation results showed that the alterations in the generation rates of O2•- and NO led to the formation of a wide range of ROS and RNS. Simulations performed by varying the ratio of O2•- to NO generation rates as well as GSH and GPX concentrations showed that the GPX reducing capacity was dependent on GSH availability, level of oxidative/nitrosative stress, and can be attributed to N2O3 levels, but not to H2O2 and ONOO-. Our results showed that N2O3 mediated switch-like depletion in GSH and the incorporation of Prx had no considerable effect on the ROS/RNS species other than ONOO- and H2O2. The analysis presented in this study will improve our understanding of vascular diseases in which the levels and oxidation states of GSH, GPX and/or Prx are significantly altered and pharmacological interventions show limited benefits.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Panday S
Department of Biomedical Engineering, Wayne State University, Detroit, MI 48202, United States of America.
Talreja R
Department of Biomedical Engineering, Wayne State University, Detroit, MI 48202, United States of America.
Kavdia M
Department of Biomedical Engineering, Wayne State University, Detroit, MI 48202, United States of America. Electronic address: kavdia@wayne.edu.

MeSH

AnimalsComputer SimulationEndothelial CellsGlutathioneGlutathione PeroxidaseHumansKineticsModels, CardiovascularNitrosative StressNumerical Analysis, Computer-AssistedOxidation-ReductionOxidative StressReactive Nitrogen SpeciesReactive Oxygen SpeciesSignal Transduction

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32335268

Citation

Panday, Sheetal, et al. "The Role of Glutathione and Glutathione Peroxidase in Regulating Cellular Level of Reactive Oxygen and Nitrogen Species." Microvascular Research, vol. 131, 2020, p. 104010.
Panday S, Talreja R, Kavdia M. The role of glutathione and glutathione peroxidase in regulating cellular level of reactive oxygen and nitrogen species. Microvasc Res. 2020;131:104010.
Panday, S., Talreja, R., & Kavdia, M. (2020). The role of glutathione and glutathione peroxidase in regulating cellular level of reactive oxygen and nitrogen species. Microvascular Research, 131, 104010. https://doi.org/10.1016/j.mvr.2020.104010
Panday S, Talreja R, Kavdia M. The Role of Glutathione and Glutathione Peroxidase in Regulating Cellular Level of Reactive Oxygen and Nitrogen Species. Microvasc Res. 2020;131:104010. PubMed PMID: 32335268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of glutathione and glutathione peroxidase in regulating cellular level of reactive oxygen and nitrogen species. AU - Panday,Sheetal, AU - Talreja,Raghav, AU - Kavdia,Mahendra, Y1 - 2020/04/23/ PY - 2019/11/25/received PY - 2020/04/20/revised PY - 2020/04/20/accepted PY - 2020/4/27/pubmed PY - 2020/11/26/medline PY - 2020/4/27/entrez KW - Antioxidants KW - Blood vessel lining KW - Computational model KW - Endothelial dysfunction KW - Nitric oxide KW - Reaction kinetics network SP - 104010 EP - 104010 JF - Microvascular research JO - Microvasc Res VL - 131 N2 - Glutathione (GSH) and GSH/glutathione peroxidase (GPX) enzyme system is essential for normal intracellular homeostasis and gets disturbed under pathophysiologic conditions including endothelial dysfunction. Overproduction of reactive oxidative species (ROS) and reactive nitrogen species (RNS) including superoxide (O2•-), and the loss of nitric oxide (NO) bioavailability is a characteristic of endothelial dysfunction. The GSH/GPX system play an important role in eliminating ROS/RNS. Studies have provided important information regarding the interactions of ROS/RNS with the GSH/GPX in biological systems; however, it is not clear how this cross talk affect these reactive species and GSH/GPX enzyme system, under physiologic and oxidative/nitrosative stress conditions. In the present study, we developed a detailed endothelial cell kinetic model to understand the relationship amongst the key enzyme systems including GSH, GPX, peroxiredoxin (Prx) and reactive species, such as hydrogen peroxide (H2O2), peroxynitrite (ONOO-), and dinitrogen trioxide (N2O3). Our simulation results showed that the alterations in the generation rates of O2•- and NO led to the formation of a wide range of ROS and RNS. Simulations performed by varying the ratio of O2•- to NO generation rates as well as GSH and GPX concentrations showed that the GPX reducing capacity was dependent on GSH availability, level of oxidative/nitrosative stress, and can be attributed to N2O3 levels, but not to H2O2 and ONOO-. Our results showed that N2O3 mediated switch-like depletion in GSH and the incorporation of Prx had no considerable effect on the ROS/RNS species other than ONOO- and H2O2. The analysis presented in this study will improve our understanding of vascular diseases in which the levels and oxidation states of GSH, GPX and/or Prx are significantly altered and pharmacological interventions show limited benefits. SN - 1095-9319 UR - https://www.unboundmedicine.com/medline/citation/32335268/The_role_of_glutathione_and_glutathione_peroxidase_in_regulating_cellular_level_of_reactive_oxygen_and_nitrogen_species_ DB - PRIME DP - Unbound Medicine ER -