Heritability of the aged glutathione phenotype is dependent on tissue of origin

Gould, Rebecca L.; Zhou, Yang; Yakaitis, Claire L.; Love, Kimberly; Reeves, Jaxk; Kong, Wenqian; Coe, E.J.; Xiao, Y.; Pazdro, Robert

doi:10.1007/s00335-018-9759-2

Cited by 7 publications

(9 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Especially, pyroglutamic acid, glutamic acid, and glutathione are involved in glutathione metabolism and were down-regulated in DSS group. The glutathione pathway is a key hepatic defense mechanism and deactivates reactive metabolites before they have the chance to damage cellular proteins [29]. In addition, we found that tryptophan metabolism was influenced significantly by IBD in our research, shown in Figure 5a.…”

Section: Dss Induced Ibd Cause Perturbations In Liver Metabolismsupporting

confidence: 55%

Metabolic profiling of liver in C57BL/6 mice with DSS-induced inﬂammatory bowel disease by untargeted metabolomics analysis

Xin

Zhai

Long

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Inﬂammatory bowel disease (IBD) is a systemic disease that frequently causes liver damage. However, the metabolic mechanism of liver disorder induced by IBD is still unclear. This study aimed to revile metabolic profiles of liver in mice which induced inﬂammatory bowel disease by dextran sulfate sodium (DSS) and treated by cecropin A and gentamicin . Methods: In this study, IBD mold mice were established, C57BL/6 mice were given water containing 2.5% dextran sulfate sodium (DSS) for 5 days. Subsequently, the mice were treated via intraperitoneally injected with saline, 15 mg/kg cecropin A, 5 mg/kg gentamicin for 3 days, respectively. The liver in IBD mold mice or treated by cecropin A and gentamicin, were performed metabolomics analysis through UPLC–Orbitrap–MS/MS. Database integration analysis software was used to identify metabolites of liver. Multivariate analysis, including principal component analysis (PCA), hierarchical cluster analysis (HCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA). Furthermore, metabolic pathway analysis was performed using MetaboAnalyst 4.0. Results: A total of 133 metabolites were identified in liver of mice and 20 key metabolites were considered as potential biomarkers were identified between the control and IBD group. There are 4 key metabolic pathways include bile acid metabolism, arachidonic acid metabolism, amino acid and protein metabolism, and steroid hormone biosynthesis in liver was disturbed by IBD, and we also found that those pathways were reversed when mice were treated by cecropin A and gentamicin. Conclusion: The results indicated that those differential metabolites and metabolic pathways changed in liver were likely to be caused by IBD. The further study shall be carried out to explore the mechanism of liver disorder induced by IBD.

show abstract

Section: Dss Induced Ibd Cause Perturbations In Liver Metabolismsupporting

confidence: 55%

Metabolic profiling of liver in C57BL/6 mice with DSS-induced inﬂammatory bowel disease by untargeted metabolomics analysis

Xin

Zhai

Long

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Although there is a great amount of information about glutathione, it is evident that there is still a lot to discover about its function in cellular regulation. In the last years, approaches to design future therapies consider novel aspects as, for example, heritability of GSH levels in different organs/tissues [ 190 ], regulation of epigenetic mechanisms as response to variations of glutathione level or GSH/GSSG ration [ 191 ]; redox signaling through the formation of mixed disulfides stimulated by hormones [ 192 ] or even, testing in animal models, a mitochondrial transplantation therapy that could increase ATP supply and reduce ROS damages [ 193 ]. Indeed, Cowan et al [ 194 ] successfully reported intracoronary exogenous mitochondrial delivery into an ischemic heart for cardioprotection.…”

Section: Discussionmentioning

confidence: 99%

Glutathione Participation in the Prevention of Cardiovascular Diseases

et al. 2021

View full text Add to dashboard Cite

Cardiovascular diseases (CVD) (such as occlusion of the coronary arteries, hypertensive heart diseases and strokes) are diseases that generate thousands of patients with a high mortality rate worldwide. Many of these cardiovascular pathologies, during their development, generate a state of oxidative stress that leads to a deterioration in the patient’s conditions associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Within these reactive species we find superoxide anion (O2•–), hydroxyl radical (•OH), nitric oxide (NO•), as well as other species of non-free radicals such as hydrogen peroxide (H2O2), hypochlorous acid (HClO) and peroxynitrite (ONOO–). A molecule that actively participates in counteracting the oxidizing effect of reactive species is reduced glutathione (GSH), a tripeptide that is present in all tissues and that its synthesis and/or regeneration is very important to be able to respond to the increase in oxidizing agents. In this review, we will address the role of glutathione, its synthesis in both the heart and the liver, and its importance in preventing or reducing deleterious ROS effects in cardiovascular diseases.

show abstract

“…The DSS group was altered in amino acid and protein metabolism, and amino acid-related compounds such as pyroglutamic acid, glutamic acid, and glutathione were involved in glutathione metabolism and downregulated in the DSS group. The glutathione pathway is a key hepatic defense mechanism and deactivates reactive metabolites before they have an opportunity to damage cellular proteins [ 27 ]. In addition, we found that tryptophan metabolism was influenced considerably by IBD in our research.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease

Xin

Zhai

Long

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

Liver disorder often occurs in patients with inflammatory bowel disease (IBD); however, the changes in IBD-induced liver disorder at the intrinsic molecular level (chiefly metabolites) and therapeutic targets are still poorly characterized. First, a refined and translationally relevant model of DSS chronic colitis in C57BL/6 mice was established, and cecropin A and antibiotics were used as interventions. We found that the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the liver tissues of mice were highly increased in the context of DSS treatment but were lowered by cecropin A and antibiotics. Subsequently, an untargeted metabolomics analysis was performed by UPLC–Orbitrap–MS/MS to reveal the metabolic profile and attempt to find the potential therapeutic targets of the liver disorders that occur in IBD. Notably, 133 metabolites were identified by an integrated database. Metabolism network and pathway analyses demonstrated that the metabolic disturbance of the liver in IBD mice was mainly enriched in bile acid metabolism, arachidonic acid metabolism, amino acid metabolism, and steroid hormone biosynthesis, while those disturbances were regulated or reversed through cecropin A and antibiotic treatment. Furthermore, the top 20 metabolites, such as glutathione, maltose, arachidonic acid, and thiamine, were screened as biomarkers via one-way analysis of variance (one-way ANOVA, p<0.05) coupled with variable importance for project values (VIP >1) of orthogonal partial least-squares discriminant analysis (OPLS-DA), which could be upregulated or downregulated with the cecropin A and antibiotics treatment. Spearman correlation analysis showed that the majority of the biomarkers have a significant correlation with cytokines (TNF-α, IL-1β, IL-6, and IL-10), indicating that those biomarkers may act as potential targets to interact directly or indirectly with cecropin A and antibiotics to affect liver inflammation. Collectively, our results extend the understanding of the molecular alteration of liver disorders occurring in IBD and offer an opportunity for discovering potential therapeutic targets in the IBD process.

show abstract

Heritability of the aged glutathione phenotype is dependent on tissue of origin

Cited by 7 publications

References 34 publications

Metabolic profiling of liver in C57BL/6 mice with DSS-induced inﬂammatory bowel disease by untargeted metabolomics analysis

Metabolic profiling of liver in C57BL/6 mice with DSS-induced inﬂammatory bowel disease by untargeted metabolomics analysis

Glutathione Participation in the Prevention of Cardiovascular Diseases

Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease

Contact Info

Product

Resources

About