Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation
Reactive oxygen species (ROS) are produced constantly inside the cells as a consequence of nutrient catabolism. The balance between ROS production and elimination allows to maintain cell redox homeostasis and biological functions, avoiding the occurrence of oxidative distress causing irreversible ox...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/10/1/19 |
| _version_ | 1797543400374796288 |
|---|---|
| author | Lidia de Bari Andrea Scirè Cristina Minnelli Laura Cianfruglia Miklos Peter Kalapos Tatiana Armeni |
| author_facet | Lidia de Bari Andrea Scirè Cristina Minnelli Laura Cianfruglia Miklos Peter Kalapos Tatiana Armeni |
| author_sort | Lidia de Bari |
| collection | DOAJ |
| description | Reactive oxygen species (ROS) are produced constantly inside the cells as a consequence of nutrient catabolism. The balance between ROS production and elimination allows to maintain cell redox homeostasis and biological functions, avoiding the occurrence of oxidative distress causing irreversible oxidative damages. A fundamental player in this fine balance is reduced glutathione (GSH), required for the scavenging of ROS as well as of the reactive 2-oxoaldehydes methylglyoxal (MGO). MGO is a cytotoxic compound formed constitutively as byproduct of nutrient catabolism, and in particular of glycolysis, detoxified in a GSH-dependent manner by the glyoxalase pathway consisting in glyoxalase I and glyoxalase II reactions. A physiological increase in ROS production (oxidative eustress, OxeS) is promptly signaled by the decrease of cellular GSH/GSSG ratio which can induce the reversible S-glutathionylation of key proteins aimed at restoring the redox balance. An increase in MGO level also occurs under oxidative stress (OxS) conditions probably due to several events among which the decrease in GSH level and/or the bottleneck of glycolysis caused by the reversible S-glutathionylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase. In the present review, it is shown how MGO can play a role as a stress signaling molecule in response to OxeS, contributing to the coordination of cell metabolism with gene expression by the glycation of specific proteins. Moreover, it is highlighted how the products of MGO metabolism, S-D-lactoylglutathione (SLG) and D-lactate, which can be taken up and metabolized by mitochondria, could play important roles in cell response to OxS, contributing to cytosol-mitochondria crosstalk, cytosolic and mitochondrial GSH pools, energy production, and the restoration of the GSH/GSSG ratio. The role for SLG and glyoxalase II in the regulation of protein function through S-glutathionylation under OxS conditions is also discussed. Overall, the data reported here stress the need for further studies aimed at understanding what role the evolutionary-conserved MGO formation and metabolism can play in cell signaling and response to OxS conditions, the aberration of which may importantly contribute to the pathogenesis of diseases associated to elevated OxS. |
| first_indexed | 2024-03-10T13:45:02Z |
| format | Article |
| id | doaj.art-e84bea2c5ef74b429f77d69dfb712ae9 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T13:45:02Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-e84bea2c5ef74b429f77d69dfb712ae92023-11-21T02:45:53ZengMDPI AGAntioxidants2076-39212020-12-011011910.3390/antiox10010019Interplay among Oxidative Stress, Methylglyoxal Pathway and S-GlutathionylationLidia de Bari0Andrea Scirè1Cristina Minnelli2Laura Cianfruglia3Miklos Peter Kalapos4Tatiana Armeni5Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), 70126 Bari, ItalyDepartment of Life Environmental Sciencesand, Università Politecnica delle Marche, 60100 Ancona, ItalyDepartment of Life Environmental Sciencesand, Università Politecnica delle Marche, 60100 Ancona, ItalyDepartment of Clinical Sciences, Università Politecnica delle Marche, 60100 Ancona, ItalyTheoretical Biology Research Group, Dámvad utca 18, H-1029 Budapest, HungaryDepartment of Clinical Sciences, Università Politecnica delle Marche, 60100 Ancona, ItalyReactive oxygen species (ROS) are produced constantly inside the cells as a consequence of nutrient catabolism. The balance between ROS production and elimination allows to maintain cell redox homeostasis and biological functions, avoiding the occurrence of oxidative distress causing irreversible oxidative damages. A fundamental player in this fine balance is reduced glutathione (GSH), required for the scavenging of ROS as well as of the reactive 2-oxoaldehydes methylglyoxal (MGO). MGO is a cytotoxic compound formed constitutively as byproduct of nutrient catabolism, and in particular of glycolysis, detoxified in a GSH-dependent manner by the glyoxalase pathway consisting in glyoxalase I and glyoxalase II reactions. A physiological increase in ROS production (oxidative eustress, OxeS) is promptly signaled by the decrease of cellular GSH/GSSG ratio which can induce the reversible S-glutathionylation of key proteins aimed at restoring the redox balance. An increase in MGO level also occurs under oxidative stress (OxS) conditions probably due to several events among which the decrease in GSH level and/or the bottleneck of glycolysis caused by the reversible S-glutathionylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase. In the present review, it is shown how MGO can play a role as a stress signaling molecule in response to OxeS, contributing to the coordination of cell metabolism with gene expression by the glycation of specific proteins. Moreover, it is highlighted how the products of MGO metabolism, S-D-lactoylglutathione (SLG) and D-lactate, which can be taken up and metabolized by mitochondria, could play important roles in cell response to OxS, contributing to cytosol-mitochondria crosstalk, cytosolic and mitochondrial GSH pools, energy production, and the restoration of the GSH/GSSG ratio. The role for SLG and glyoxalase II in the regulation of protein function through S-glutathionylation under OxS conditions is also discussed. Overall, the data reported here stress the need for further studies aimed at understanding what role the evolutionary-conserved MGO formation and metabolism can play in cell signaling and response to OxS conditions, the aberration of which may importantly contribute to the pathogenesis of diseases associated to elevated OxS.https://www.mdpi.com/2076-3921/10/1/19glyoxalase systemglutathioneglutathionylationmitochondriamethylglyoxalS-D-lactoylglutathione |
| spellingShingle | Lidia de Bari Andrea Scirè Cristina Minnelli Laura Cianfruglia Miklos Peter Kalapos Tatiana Armeni Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation Antioxidants glyoxalase system glutathione glutathionylation mitochondria methylglyoxal S-D-lactoylglutathione |
| title | Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation |
| title_full | Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation |
| title_fullStr | Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation |
| title_full_unstemmed | Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation |
| title_short | Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation |
| title_sort | interplay among oxidative stress methylglyoxal pathway and s glutathionylation |
| topic | glyoxalase system glutathione glutathionylation mitochondria methylglyoxal S-D-lactoylglutathione |
| url | https://www.mdpi.com/2076-3921/10/1/19 |
| work_keys_str_mv | AT lidiadebari interplayamongoxidativestressmethylglyoxalpathwayandsglutathionylation AT andreascire interplayamongoxidativestressmethylglyoxalpathwayandsglutathionylation AT cristinaminnelli interplayamongoxidativestressmethylglyoxalpathwayandsglutathionylation AT lauracianfruglia interplayamongoxidativestressmethylglyoxalpathwayandsglutathionylation AT miklospeterkalapos interplayamongoxidativestressmethylglyoxalpathwayandsglutathionylation AT tatianaarmeni interplayamongoxidativestressmethylglyoxalpathwayandsglutathionylation |