Butyrate Rescues Oxidative Stress-Induced Transport Deficits of Tryptophan: Potential Implication in Affective or Gut-Brain Axis Disorders

2020 ◽  
pp. 1-11
Author(s):  
Julia Rode ◽  
Lin Yang ◽  
Julia König ◽  
Ashley Nicole Hutchinson ◽  
Rebecca Wall ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Amino Acid ◽  
Affective Disorders ◽  
Expression Profiles ◽  
Human Fibroblasts ◽  
Antioxidant Properties ◽  
Amino Acid Transporters ◽  
Potential Implication ◽  
Cellular Models

<b><i>Introduction:</i></b> Butyrate is a short-chain fatty acid metabolite produced by microbiota in the colon. With its antioxidant properties, butyrate has also been shown to alter the neurological functions in affective disorder models, suggesting it as a key mediator in gut-brain interactions. <b><i>Objective:</i></b> Here, we evaluated the negative effect of oxidative stress on the transport of the serotonin precursor tryptophan as present in affective disorders. Butyrate was hypothesized to be able to rescue these deficits due to its antioxidative capacities and its effect on transmembrane transport of tryptophan. Human skin-derived fibroblasts were used as cellular models to address these objectives. <b><i>Methods:</i></b> Human fibroblasts were treated with hydrogen peroxide to induce oxidative stress. Stressed as well as control cells were treated with different concentrations of butyrate. Tryptophan (<sup>3</sup>H) was used as a tracer to measure the transport of tryptophan across the cell membranes (<i>n</i> = 6). Furthermore, gene expression profiles of different amino acid transporters were analyzed (<i>n</i> = 2). <b><i>Results:</i></b> As hypothesized,<b><i></i></b>oxidative stress significantly decreased the uptake of tryptophan in fibroblast cells, while butyrate counteracted this effect. Oxidative stress did not alter the gene expression profile of amino acid transporters. However, treatment of stressed and control cells with different concentrations of butyrate differentially regulated the gene expression of large amino acid transporters 1 and 2, which are the major transporters of tryptophan. <b><i>Conclusions:</i></b>Gut microbiota-derived butyrate may have therapeutic potential in affective disorders characterized by either aberrant serotonergic activity or neuroinflammation due to its role in rescuing the oxidative stress-induced perturbations of tryptophan transport.

scholarly journals Dietary methionine level alters growth, digestibility, and gene expression of amino acid transporters in meat-type chickens

2020 ◽  
Vol 99 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Naiara S. Fagundes ◽  
Marie C. Milfort ◽  
Susan M. Williams ◽  
Manuel J. Da Costa ◽  
Alberta L. Fuller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Amino Acid Transporters ◽  
Methionine Level ◽  
Meat Type

scholarly journals Effects of glutamine supplementation on oxidative stress-related gene expression and antioxidant properties in rats with streptozotocin-induced type 2 diabetes

2011 ◽  
Vol 107 (8) ◽  
pp. 1112-1118 ◽  
Author(s):  
Pei-Hsuan Tsai ◽  
Jun-Jen Liu ◽  
Chui-Li Yeh ◽  
Wan-Chun Chiu ◽  
Sung-Ling Yeh
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Amino Acid ◽  
Oxidative Damage ◽  
Antioxidant Capacity ◽  
Enzyme Activities ◽  
Antioxidant Enzyme Activities ◽  
Related Gene ◽  
Gene Expressions ◽  
Oxidative Stress Related Gene

There are close links among hyperglycaemia, oxidative stress and diabetic complications. Glutamine (GLN) is an amino acid with immunomodulatory properties. The present study investigated the effect of dietary GLN on oxidative stress-relative gene expressions and tissue oxidative damage in diabetes. There were one normal control (NC) and two diabetic groups in the present study. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin (STZ). Rats in the NC group were fed a regular chow diet. In the two diabetic groups, one group (diabetes mellitus, DM) was fed a common semi-purified diet while the other group received a diet in which part of the casein was replaced by GLN (DM-GLN). GLN provided 25 % of total amino acid N. The experimental groups were fed the respective diets for 8 weeks, and then the rats were killed for further analysis. The results showed that blood thioredoxin-interacting protein (Txnip) mRNA expression in the diabetic groups was higher than that in the NC group. Compared with the DM group, the DM-GLN group had lower glutamine fructose-6-phosphate transaminase 1, a receptor of advanced glycation end products, and Txnip gene expressions in blood mononuclear cells. The total antioxidant capacity was lower and antioxidant enzyme activities were altered by the diabetic condition. GLN supplementation increased antioxidant capacity and normalised antioxidant enzyme activities. Also, the renal nitrotyrosine level and Txnip mRNA expression were lower when GLN was administered. These results suggest that dietary GLN supplementation decreases oxidative stress-related gene expression, increases the antioxidant potential and may consequently attenuate renal oxidative damage in rats with STZ-induced diabetes.

Epicatechin and its in vivo metabolite, 3′-O-methyl epicatechin, protect human fibroblasts from oxidative-stress-induced cell death involving caspase-3 activation

2001 ◽  
Vol 354 (3) ◽  
pp. 493-500 ◽  
Author(s):  
Jeremy P. E. SPENCER ◽  
Hagen SCHROETER ◽  
Gunter KUHNLE ◽  
S. Kaila S. SRAI ◽  
Rex M. TYRRELL ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Caspase 3 ◽  
Cell Damage ◽  
Protective Action ◽  
Human Fibroblasts ◽  
Membrane Damage ◽  
Antioxidant Properties

There is considerable current interest in the cytoprotective effects of natural antioxidants against oxidative stress. In particular, epicatechin, a major member of the flavanol family of polyphenols with powerful antioxidant properties in vitro, has been investigated to determine its ability to attenuate oxidative-stress-induced cell damage and to understand the mechanism of its protective action. We have induced oxidative stress in cultured human fibroblasts using hydrogen peroxide and examined the cellular responses in the form of mitochondrial function, cell-membrane damage, annexin-V binding and caspase-3 activation. Since one of the major metabolites of epicatechin in vivo is 3′-O-methyl epicatechin, we have compared its protective effects with that of epicatechin. The results provide the first evidence that 3′-O-methyl epicatechin inhibits cell death induced by hydrogen peroxide and that the mechanism involves suppression of caspase-3 activity as a marker for apoptosis. Furthermore, the protection elicited by 3′-O-methyl epicatechin is not significantly different from that of epicatechin, suggesting that hydrogen-donating antioxidant activity is not the primary mechanism of protection.

Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue reveals distinct cytokine and chemokine expression patterns

2003 ◽  
Vol 90 (10) ◽  
pp. 688-697 ◽  
Author(s):  
Andrew Filer ◽  
Ewan Ross ◽  
Margarita Bofill ◽  
Stuart Martin ◽  
Mike Salmon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Human Fibroblasts ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Synovial Fibroblasts ◽  
Skin Fibroblasts ◽  
Inflammatory Reactions ◽  
Tnf Α

SummaryWe investigated the extent to which fibroblasts isolated from diverse tissues differ in their capacity to modulate inflammation by comparing the global gene expression profiles of cultured human fibroblasts from skin, acute and chronically inflamed synovium, lymph node and tonsil. The responses of these fibroblasts to TNF-α, IFN-γ and IL-4 stimulation were markedly different, as revealed by hierarchical cluster analysis and principal component analysis. In the absence of exogenous cytokine, syn-ovial and skin fibroblasts exhibited similar patterns of gene expression. However their transcriptional profiles diverged upon treatment with TNF-α.This proved to be biologically relevant, as TNF-α induced the secretion of different patterns and amounts of IL-6, IL-8 and CCL2 (MCP-1) in the two fibroblast types. Co-culture of skin or synovial fibroblasts with synovial fluid-derived mononuclear cells provided further evidence that these transcriptional differences were functionally significant in an ex vivo setting. Interestingly, the transcriptional response of skin fibroblasts to IL-4 converged with that of TNF-α-treated synovial fibroblasts, suggesting resident tissue fibroblasts and their blood-borne precursors may be imprinted by inflammatory cytokines that are characteristic of different tissues. Our data supports the concept that fibroblasts are heterogeneous, and that they contribute to the tissue-specificity of inflammatory reactions. Fibroblasts are therefore likely to play an active role in the persistence of chronic inflammatory reactions.This publication was partially financed by Serono Foundation for the Advancement of Medical Science.Part of this paper was originally presented at the 2nd International Workshop on New Therapeutic Targets in Vascular Biology from February 6-9, 2003 in Geneva, Switzerland.

scholarly journals Ezetimibe Prevents Ischemia/Reperfusion-Induced Oxidative Stress and Up-Regulates Nrf2/ARE and UPR Signaling Pathways

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 349 ◽  
Author(s):  
Denise Peserico ◽  
Chiara Stranieri ◽  
Ulisse Garbin ◽  
Chiara Mozzini C ◽  
Elisa Danese ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cultured Cells ◽  
Ischemia Reperfusion ◽  
Cholesterol Absorption ◽  
Antioxidant Response ◽  
Related Factor ◽  
Cellular Models ◽  
Compound C ◽  
Cholesterol Absorption Inhibitor

Background: While reperfusion is crucial for survival after an episode of ischemia, it also causes oxidative stress. Nuclear factor-E2-related factor 2 (Nrf2) and unfolded protein response (UPR) are protective against oxidative stress and endoplasmic reticulum (ER) stress. Ezetimibe, a cholesterol absorption inhibitor, has been shown to activate the AMP-activated protein kinase (AMPK)/Nrf2 pathway. In this study we evaluated whether Ezetimibe affects oxidative stress and Nrf2 and UPR gene expression in cellular models of ischemia-reperfusion (IR). Methods: Cultured cells were subjected to simulated IR with or without Ezetimibe. Results: IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). Ezetimibe significantly decreased the cellular ROS formation and apoptosis induced by IR. These effects were paralleled by the up-regulation of Nrf2/ARE and ATF6 gene expression and by a down-regulation of CHOP. We also found that Nrf2 activation was dependent on AMPK, since Compound C, a pan inhibitor of p-AMPK, blunted the activation of Nrf2. Conclusions: Ezetimibe counteracts IR-induced oxidative stress and induces Nrf2 and UPR pathway activation.

scholarly journals Identification of Hub Prognosis-Associated Oxidative Stress Genes in Pancreatic Cancer Using Integrated Bioinformatics Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Xin Qiu ◽  
Qin-Han Hou ◽  
Qiu-Yue Shi ◽  
Hai-Xing Jiang ◽  
Shan-Yu Qin
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Risk Model ◽  
Cox Regression ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Cox Regression Analysis

BackgroundIntratumoral oxidative stress (OS) has been associated with the progression of various tumors. However, OS has not been considered a candidate therapeutic target for pancreatic cancer (PC) owing to the lack of validated biomarkers.MethodsWe compared gene expression profiles of PC samples and the transcriptome data of normal pancreas tissues from The Cancer Genome Atlas (TCGA) and Genome Tissue Expression (GTEx) databases to identify differentially expressed OS genes in PC. PC patients’ gene profile from the Gene Expression Omnibus (GEO) database was used as a validation cohort.ResultsA total of 148 differentially expressed OS-related genes in PC were used to construct a protein-protein interaction network. Univariate Cox regression analysis, least absolute shrinkage, selection operator analysis revealed seven hub prognosis-associated OS genes that served to construct a prognostic risk model. Based on integrated bioinformatics analyses, our prognostic model, whose diagnostic accuracy was validated in both cohorts, reliably predicted the overall survival of patients with PC and cancer progression. Further analysis revealed significant associations between seven hub gene expression levels and patient outcomes, which were validated at the protein level using the Human Protein Atlas database. A nomogram based on the expression of these seven hub genes exhibited prognostic value in PC.ConclusionOur study provides novel insights into PC pathogenesis and provides new genetic markers for prognosis prediction and clinical treatment personalization for PC patients.

scholarly journals Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: implications for cellular senescence

2008 ◽  
Vol 389 (3) ◽  
pp. 243-255 ◽  
Author(s):  
Kotb Abdelmohsen ◽  
Yuki Kuwano ◽  
Hyeon Ho Kim ◽  
Myriam Gorospe
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cellular Senescence ◽  
Mammalian Cells ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Oxidant Damage ◽  
Regulated Gene Expression

AbstractTo respond adequately to oxidative stress, mammalian cells elicit rapid and tightly controlled changes in gene expression patterns. Besides alterations in the subsets of transcribed genes, two posttranscriptional processes prominently influence the oxidant-triggered gene expression programs: mRNA turnover and translation. Here, we review recent progress in our knowledge of theturnover andtranslationregulatory (TTR) mRNA-bindingproteins (RBPs) that influence gene expression in response to oxidative damage. Specifically, we identify oxidant damage-regulated mRNAs that are targets of TTR-RBPs, we review the oxidant-triggered signaling pathways that govern TTR-RBP function, and we examine emerging evidence that TTR-RBP activity is altered with senescence and aging. Given the potent influence of TTR-RBPs upon oxidant-regulated gene expression profiles, we propose that the senescence-associated changes in TTR-RBPs directly contribute to the impaired responses to oxidant damage that characterize cellular senescence and advancing age.

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