GSTP1 as a novel target in radiation induced lung injury

Xiao, Lanbo; Du, Le; Wang, Yu; Wang, Yao; Ma, Ning; Qu, Baolin

doi:10.1186/s12967-021-02978-0

“…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%

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

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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.

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“…Previous studies ruled out that Gstp1 is closely involved in the inhibition of cell apoptosis and regulation of cell oxidative stress ( 64 , 65 ). The tumor necrosis factor-related receptor 2 (TRAF2) interacts with apoptosis signal regulating kinase 1 (ASK1), and the interaction between them could be abolished by binding Gstp1 to TRAF2 ( 66 ). Gstp1 regulated the ASK1-MEK-JNK/p38 pathway negatively and inhibited cell apoptosis ( 67 ).…”

Section: Discussionmentioning

confidence: 99%

The effect of G0S2 on insulin sensitivity: A proteomic analysis in a G0S2-overexpressed high-fat diet mouse model

Wu

¹

,

Zhang

²

,

Sun

³

et al. 2023

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BackgroundPrevious research has shown a tight relationship between the G0/G1 switch gene 2 (G0S2) and metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and obesity and diabetes, and insulin resistance has been shown as the major risk factor for both NAFLD and T2DM. However, the mechanisms underlying the relationship between G0S2 and insulin resistance remain incompletely understood. Our study aimed to confirm the effect of G0S2 on insulin resistance, and determine whether the insulin resistance in mice fed a high-fat diet (HFD) results from G0S2 elevation.MethodsIn this study, we extracted livers from mice that consumed HFD and received tail vein injections of AD-G0S2/Ad-LacZ, and performed a proteomics analysis.ResultsProteomic analysis revealed that there was a total of 125 differentially expressed proteins (DEPs) (56 increased and 69 decreased proteins) among the identified 3583 proteins. Functional enrichment analysis revealed that four insulin signaling pathway-associated proteins were significantly upregulated and five insulin signaling pathway -associated proteins were significantly downregulated.ConclusionThese findings show that the DEPs, which were associated with insulin resistance, are generally consistent with enhanced insulin resistance in G0S2 overexpression mice. Collectively, this study demonstrates that G0S2 may be a potential target gene for the treatment of obesity, NAFLD, and diabetes.

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“…It is believed that the main mechanism is that when the lung tissue is under radiation, a large amount of reactive oxygen species can be produced, and act on the alveolar epithelial cells and vascular endothelial cells, causing a large number of cells to undergo apoptosis and damage the barrier function of the lung tissue [1,3]. Therefore, a lot of research has been carried out using natural antioxidants to perevent RILI [43,44]. Mitochondria, as an important site of ROS and energy metabolism, may play a key role in the prevention of RILI [45].…”

Section: Discussionmentioning

confidence: 99%

Monophosphoryl lipid A ameliorates radiation-induced lung injury by promoting the polarization of macrophages to the M1 phenotype

Guo

¹

,

Du

²

,

Ma

³

et al. 2022

Self Cite

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Background Radiation-induced lung injury (RILI) often occurs during clinical chest radiotherapy and acute irradiation from accidental nuclear leakage. This study explored the role of monophosphoryl lipid A (MPLA) in RILI. Materials and Methods The entire thoracic cavity of C57BL/6N mice was irradiated at 20 Gy with or without pre-intragastric administration of MPLA. HE staining, Masson trichrome staining, and TUNEL assay were used to assess lung tissue injury after treatment. The effect of irradiation on the proliferation of MLE-12 cells was analyzed using the Clonogenic assay. The effect of MPLA on the apoptosis of MLE-12 cells was analyzed using flow cytometry. Expression of γ-H2AX and epithelial-mesenchymal transition (EMT) markers in MLE-12 cells was detected by immunofluorescence and Western blot, respectively. Results MPLA attenuated early pneumonitis and late pulmonary fibrosis after thoracic irradiation and reversed radiation-induced EMT in C57 mice. MPLA further promoted proliferation and inhibited apoptosis of irradiated MLE-12 cells in vitro. Mechanistically, the radioprotective effect of MPLA was mediated by exosomes secreted by stimulated macrophages. Macrophage-derived exosomes modulated DNA damage in MLE-12 cells after irradiation. MPLA promoted the polarization of RAW 264.7 cells to the M1 phenotype. The exosomes secreted by M1 macrophages suppressed EMT in MLE-12 cells after irradiation. Conclusion MPLA is a novel treatment strategy for RILI. Exosomes derived from macrophages are key to the radioprotective role of MPLA in RILI.

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GSTP1 as a novel target in radiation induced lung injury

Cited by 15 publications

References 68 publications

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

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

The effect of G0S2 on insulin sensitivity: A proteomic analysis in a G0S2-overexpressed high-fat diet mouse model

Monophosphoryl lipid A ameliorates radiation-induced lung injury by promoting the polarization of macrophages to the M1 phenotype

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