Role of Glutaredoxin-1 and Glutathionylation in Cardiovascular Diseases

Burns, Mannix J.; Rizvi, Syed Husain Mustafa; Tsukahara, Yusuke; Pimentel, David R.; Luptak, Ivan; Hamburg, Naomi M.; Matsui, Reiko; Bachschmid, Markus

doi:10.3390/ijms21186803

“…Based on the comprehensive analysis from StarBase, dual-luciferase reporter assay and RIP assay, we identified GLRX as a direct target of miR-132-3p . GLRX is an indispensable thioltransferase whose main function is to remove protein glutathionylation ( Burns et al, 2020 ). Herein, the lowly expressed GLRX was observed in the midbrain tissues of PD patients.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease

Gong

¹

,

Huang

²

,

Chen

³

2022

eNeuro

View full text Add to dashboard Cite

The major pathology in Parkinson's disease (PD) is neuron injury induced by degeneration of dopaminergic neurons and the activation of microglial cells. The objective of this study is to determine the effect and mechanism of miR-132-3p in regulating neuroinflammation and the degeneration of dopaminergic neuron in PD.The expressions of miR-132-3p in brain tissues of PD patients, LPS induced BV-2 cells and MPTP induced PD mouse models were detected. The effect of miR-132-3p and GLRX in cell viability, apoptosis and inflammation was verified in BV-2 cells.The activation of Iba1 in substantia nigra pars compacta and the loss of tyrosine hydroxylase were detected in PD mouse models and the mobility of mouse models was assessed as well. The targeting relationship between miR-132-3p and GLRX was confirmed by RIP and dual luciferase reporter gene assay. Elevated expression of miR-132-3p and decreased expression of GLRX were found in PD patients and cells models. Overexpression of miR-132-3p can induce activation of microglial cells, which can be reversed by GLRX overexpression. Collected evidence in both cell model and mouse models showed the effect of miR-132-3p in enhancing the activation of microglial cells and the loss of microglia cells, which was achieved by mediating GLRX.

show abstract

“…Although the details of GSH involvement in these processes are not yet fully understood, the importance of the protective function of this aminothiol is emphasized both by its direct antioxidant activity and the key role of GSH-dependent enzymes that carry out (de)glutathionylation of proteins and the GSH hydrolysis. The role of glutathione S-transferase (GST) P1, glutathione transferase omega 1 (GSTO1-1), γ -glutamyl transpeptidase (GGT), and glutaredoxin in the activation of endothelial cells, smooth muscle cells, and macrophages is being actively studied [ 27 – 30 ]. The deficiency of the GSH redox cycle (GSH-peroxidase and GST) enzymes observed in the atherosclerotic plaques area contributes to the creation of a prooxidant environment within the vascular wall [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Glutathionylation of glutaredoxin-1 is also likely to be involved in the regulation of the Akt-dependent signaling pathway and is important for maintaining the physiological level of vascular permeability [ 33 , 37 ]. In addition, the disturbance of laminar flow, observed in the areas most susceptible to atherosclerotic changes, negatively affects the activity of glutaredoxin-1 [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Association of Low Molecular Weight Plasma Aminothiols with the Severity of Coronavirus Disease 2019

Kryukov¹,

Ivanov

²

,

Karpov³

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Objective. Aminothiols (glutathione (GSH), cysteinylglycine (CG)) may play an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), but the possible association of these indicators with the severity of COVID-19 has not yet been investigated. Methods. The total content ( t ) and reduced forms ( r ) of aminothiols were determined in patients with COVID-19 ( n = 59 ) on admission. Lung injury was characterized by computed tomography (CT) findings in accordance with the CT0-4 classification. Results. Low tGSH level was associated with the risk of severe COVID-19 ( tGSH ≤ 1.5 μ M , mild vs. moderate/severe: risk ratio RR = 3.09 , p = 0.007 ) and degree of lung damage ( tGSH ≤ 1.8 μ M , CT < 2 vs. CT ≥ 2 : RR = 2.14 , p = 0.0094 ). The rGSH level showed a negative association with D-dimer levels ( ρ = − 0.599 , p = 0.014 ). Low rCG level was also associated with the risk of lung damage ( rCG ≤ 1.3 μ M , CT < 2 vs. CT ≥ 2 : RR = 2.28 , p = 0.001 ). Levels of rCG ( ρ = − 0.339 , p = 0.012 ) and especially tCG ( ρ = − 0.551 , p = 0.004 ) were negatively associated with platelet count. In addition, a significant relationship was found between the advanced oxidation protein product level and tGSH in patients with moderate or severe but not in patients with mild COVID-19. Conclusion. Thus, tGSH and rCG can be seen as potential markers for the risk of severe COVID-19. GSH appears to be an important factor to oxidative damage prevention as infection progresses. This suggests the potential clinical efficacy of correcting glutathione metabolism as an adjunct therapy for COVID-19.

show abstract

“…In the traditional classification, they are divided into mono- and dithiol Grx, depending on whether one or two cysteine residues, respectively, are in the active center. The role of dithiol Grxs is mainly considered in the regulation of reversible S-glutathionylation [ 26 , 43 , 44 ].…”

Section: Glutathione and Protein S-glutathionylationmentioning

confidence: 99%

Glutathione in Protein Redox Modulation through S-Glutathionylation and S-Nitrosylation

Калинина

¹

,

Novichkova

²

2021

View full text Add to dashboard Cite

S-glutathionylation and S-nitrosylation are reversible post-translational modifications on the cysteine thiol groups of proteins, which occur in cells under physiological conditions and oxidative/nitrosative stress both spontaneously and enzymatically. They are important for the regulation of the functional activity of proteins and intracellular processes. Connecting link and “switch” functions between S-glutathionylation and S-nitrosylation may be performed by GSNO, the generation of which depends on the GSH content, the GSH/GSSG ratio, and the cellular redox state. An important role in the regulation of these processes is played by Trx family enzymes (Trx, Grx, PDI), the activity of which is determined by the cellular redox status and depends on the GSH/GSSG ratio. In this review, we analyze data concerning the role of GSH/GSSG in the modulation of S-glutathionylation and S-nitrosylation and their relationship for the maintenance of cell viability.

show abstract

Role of Glutaredoxin-1 and Glutathionylation in Cardiovascular Diseases

Cited by 27 publications

References 135 publications

Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease

Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease

Association of Low Molecular Weight Plasma Aminothiols with the Severity of Coronavirus Disease 2019

Glutathione in Protein Redox Modulation through S-Glutathionylation and S-Nitrosylation

Contact Info

Product

Resources

About