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Article ; Online: Mitochondrial and cytosolic sources of hydrogen peroxide in resting C2C12 myoblasts.

Wong, Hoi-Shan / Benoit, Bérengère / Brand, Martin D

2018 Volume 130, Page(s) 140–150

Abstract: The relative contributions of different mitochondrial and cytosolic sources of superoxide and hydrogen peroxide in cells are not well established because of a lack of suitable quantitative assays. To address this problem using resting C2C12 myoblasts we ... ...

Abstract	The relative contributions of different mitochondrial and cytosolic sources of superoxide and hydrogen peroxide in cells are not well established because of a lack of suitable quantitative assays. To address this problem using resting C2C12 myoblasts we measured the effects of specific inhibitors that do not affect other pathways on the rate of appearance of hydrogen peroxide in the extracellular medium. We used inhibitors of NADPH oxidases (NOXs), suppressors of site I
MeSH term(s)	Animals ; Catalytic Domain ; Cells, Cultured ; Cellular Senescence ; Cytosol/metabolism ; Female ; Hydrogen Peroxide/metabolism ; Mice ; Mice, Inbred C3H ; Mitochondria/metabolism ; Myoblasts, Skeletal/physiology ; NADPH Oxidases/antagonists & inhibitors ; NADPH Oxidases/metabolism ; Pyrazoles/pharmacology ; Pyridones/pharmacology ; Rats ; Rats, Wistar
Chemical Substances	2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo(4,3-c)pyridine-3,6(2H,5H)-dione ; Pyrazoles ; Pyridones ; Hydrogen Peroxide (BBX060AN9V) ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2018-10-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2018.10.448
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Article ; Online: Treatment with fibroblast growth factor 19 increases skeletal muscle fiber size, ameliorates metabolic perturbations and hepatic inflammation in 5/6 nephrectomized mice.

Benoit, Berengère / Beau, Alice / Bres, Émilie / Chanon, Stéphanie / Pinteur, Claudie / Vieille-Marchiset, Aurélie / Jalabert, Audrey / Zhang, Hao / Garg, Priyanka / Strigini, Maura / Vico, Laurence / Ruzzin, Jérôme / Vidal, Hubert / Koppe, Laetitia

Scientific reports

2023 Volume 13, Issue 1, Page(s) 5520

Abstract: Chronic kidney disease (CKD) is associated with osteosarcopenia, and because a physical decline in patients correlates with an increased risk of morbidity, an improvement of the musculoskeletal system is expected to improve morbi-mortality. We recently ... ...

Abstract	Chronic kidney disease (CKD) is associated with osteosarcopenia, and because a physical decline in patients correlates with an increased risk of morbidity, an improvement of the musculoskeletal system is expected to improve morbi-mortality. We recently uncovered that the intestinal hormone Fibroblast Growth Factor 19 (FGF19) is able to promote skeletal muscle mass and strength in rodent models, in addition to its capacity to improve glucose homeostasis. Here, we tested the effects of a treatment with recombinant human FGF19 in a CKD mouse model, which associates sarcopenia and metabolic disorders. In 5/6 nephrectomized (5/6Nx) mice, subcutaneous FGF19 injection (0.1 mg/kg) during 18 days increased skeletal muscle fiber size independently of food intake and weight gain, associated with decreased gene expression of myostatin. Furthermore, FGF19 treatment attenuated glucose intolerance and reduced hepatic expression of gluconeogenic genes in uremic mice. Importantly, the treatment also decreased gene expression of liver inflammatory markers in CKD mice. Therefore, our results suggest that FGF19 may represent a novel interesting therapeutic strategy for a global improvement of sarcopenia and metabolic complications in CKD.
MeSH term(s)	Animals ; Humans ; Mice ; Fibroblast Growth Factors/pharmacology ; Inflammation/pathology ; Muscle Fibers, Skeletal/metabolism ; Muscle, Skeletal/metabolism ; Renal Insufficiency, Chronic/complications ; Sarcopenia/pathology
Chemical Substances	Fibroblast Growth Factors (62031-54-3)
Language	English
Publishing date	2023-04-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-31874-4
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Article ; Online: Indoxyl sulfate inhibits muscle cell differentiation via Myf6/MRF4 and MYH2 downregulation.

Bataille, Stanislas / McKay, Nathalie / Koppe, Laetitia / Beau, Alice / Benoit, Bérengère / Bartoli, Marc / Da Silva, Nathalie / Poitevin, Stéphane / Aniort, Julien / Chermiti, Rania / Burtey, Stéphane / Dou, Laetitia

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

2023 Volume 39, Issue 1, Page(s) 103–113

Abstract: Background: Chronic kidney disease (CKD) is associated with a significant decrease in muscle strength and mass, possibly related to muscle cell damage by uremic toxins. Here, we studied in vitro and in vivo the effect of indoxyl sulfate (IS), an indolic ...

Abstract	Background: Chronic kidney disease (CKD) is associated with a significant decrease in muscle strength and mass, possibly related to muscle cell damage by uremic toxins. Here, we studied in vitro and in vivo the effect of indoxyl sulfate (IS), an indolic uremic toxin, on myoblast proliferation, differentiation and expression of myogenic regulatory factors (MRF)-myoblast determination protein 1 (MyoD1), myogenin (Myog), Myogenic Factor 5 (Myf5) and myogenic regulatory factor 4 (Myf6/MRF4)-and expression of myosin heavy chain, Myh2. Methods: C2C12 myoblasts were cultured in vitro and differentiated in myotubes for 7 days in the presence of IS at a uremic concentration of 200 µM. Myocytes morphology and differentiation was analyzed after hematoxylin-eosin staining. MRF genes' expression was studied using reverse transcription polymerase chain reaction in myocytes and 5/6th nephrectomized mice muscle. Myf6/MRF4 protein expression was studied using enzyme-linked immunosorbent assay; MYH2 protein expression was studied using western blotting. The role of Aryl Hydrocarbon Receptor (AHR)-the cell receptor of IS-was studied by adding an AHR inhibitor into the cell culture milieu. Results: In the presence of IS, the myotubes obtained were narrower and had fewer nuclei than control myotubes. The presence of IS during differentiation did not modify the gene expression of the MRFs Myf5, MyoD1 and Myog, but induced a decrease in expression of Myf6/MRF4 and MYH2 at the mRNA and the protein level. AHR inhibition by CH223191 did not reverse the decrease in Myf6/MRF4 mRNA expression induced by IS, which rules out the implication of the ARH genomic pathway. In 5/6th nephrectomized mice, the Myf6/MRF4 gene was down-regulated in striated muscles. Conclusion: In conclusion, IS inhibits Myf6/MRF4 and MYH2 expression during differentiation of muscle cells, which could lead to a defect in myotube structure. Through these new mechanisms, IS could participate in muscle atrophy observed in CKD.
MeSH term(s)	Animals ; Mice ; Indican/pharmacology ; Down-Regulation ; Cell Differentiation/genetics ; Muscle, Skeletal ; RNA, Messenger ; Renal Insufficiency, Chronic
Chemical Substances	myogenic factor 6 ; Indican (N187WK1Y1J) ; RNA, Messenger
Language	English
Publishing date	2023-06-22
Publishing country	England
Document type	Journal Article
ZDB-ID	90594-x
ISSN	1460-2385 ; 0931-0509
ISSN (online)	1460-2385
ISSN	0931-0509
DOI	10.1093/ndt/gfad123
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Article ; Online: Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice.

Bravard, Amélie / Gérard, Céline / Defois, Clémence / Benoit, Bérengère / Makki, Kassem / Meugnier, Emmanuelle / Rainteau, Dominique / Rieusset, Jennifer / Godet, Murielle / Vidal, Hubert

Scientific reports

2021 Volume 11, Issue 1, Page(s) 16684

Abstract: Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, it is well accepted that the gut plays an important role. To gain more insights into the mechanisms occurring in the different regions of the intestine, ...

Abstract	Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, it is well accepted that the gut plays an important role. To gain more insights into the mechanisms occurring in the different regions of the intestine, adult male mice were fed a high-fat-high sucrose (HFS) diet for 8 days and treated with metformin by gavage (300 mg/day/kg body weight) during the HFS diet. Metformin counteracted HFS diet-induced overexpression of a network of genes involved in the transport of glucose and fatty acids in the different regions of the small intestine. It also induced beneficial modification of secondary bile acid profile in the caecum, with a reduction of deoxycholic acid and lithocholic acid levels and increased abundance of ursodeoxycholic acid and tauroursodeoxycholic acid, potentially leading to FRX inhibition. In parallel, metformin treatment was associated with specific changes of the microbiota composition in the lumen of the different regions of the intestine. Metformin induced a marked increase in the abundance of Akkermansia muciniphila in the lumen all along the gut and counteracted the effects of HFS diet on the abundances of some bacterial groups generally associated with metabolic disturbances (f-Lachnospiraceae, f-Petostreptococcaceae, g-Clostidium). Therefore, the present work clearly emphasises the role of all the regions of the intestinal tract in the beneficial action of the antidiabetic drug metformin in a prediabetic mouse model.
MeSH term(s)	Animals ; Diet, Carbohydrate Loading/adverse effects ; Dietary Sucrose/metabolism ; Gastrointestinal Microbiome/drug effects ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Intestines/drug effects ; Male ; Metformin/pharmacology ; Metformin/therapeutic use ; Mice ; Mice, Inbred C57BL ; Prediabetic State/drug therapy ; Prediabetic State/etiology ; Prediabetic State/metabolism ; Prediabetic State/microbiology
Chemical Substances	Dietary Sucrose ; Hypoglycemic Agents ; Metformin (9100L32L2N)
Language	English
Publishing date	2021-08-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-95117-0
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Article: The protein-bound uremic toxin p-cresyl-sulfate promotes intracellular ROS production and lipid peroxidation in 3T3-L1 adipose cells

Koppe, Laetitia / Croze, Marine L. / Monteiro, Elisa B. / Benoit, Bérengère / Bres, Emilie / Guebre-Egziabher, Fitsum / Daleprane, Julio B. / Fouque, Denis / Soulage, Christophe O.

Biochimie. 2021 Oct., v. 189

2021

Abstract: Patients with chronic kidney disease (CKD) often exhibit increased level of oxidative stress that contribute to the deterioration of renal function and uremic complications. White adipose tissue (WAT) has been recognized as a major site of production of ... ...

Abstract	Patients with chronic kidney disease (CKD) often exhibit increased level of oxidative stress that contribute to the deterioration of renal function and uremic complications. White adipose tissue (WAT) has been recognized as a major site of production of radical oxygen species (ROS) in the context of metabolic diseases. This study was designed to decipher whether the protein bound uremic toxin p-cresyl-sulfate (p-CS) could contribute to ROS production in WAT and promote oxidative stress. Mouse 3T3-L1 adipocytes were incubated for 2 h in culture medium containing 212 μM p-CS, a concentration chosen to mimic levels encountered in end stage renal disease patients or KCl as a control and intracellular ROS production was measured using the fluorescent probe 5-6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate. Oxidative insult was estimated by the measurement of malondialdehyde (MDA) content and glutathione content. The effects of probenecid (1 mM) a potent inhibitor of organic anion transporter, apocynin (1 mM) an inhibitor of NADPH oxidase or common antioxidants such as α-tocopherol (2.5 μM), ascorbate (200 μM), and N-acetylcysteine (500 μM) were further evaluated. p-CS triggered a striking increase in ROS production (+228%, p < 0.01), in MDA content (+214%, p < 0.005) and a decrease in glutathione (−47%, P < 0.01). Pre-treatment of cells with probenecid, apocynin or antioxidants prevented the p-CS induced ROS production and oxidative insults. These results suggest that in uremic state, the intracellular accumulation of p-CS in adipose cells could contribute, through an activation of NADPH oxidase, to the redox imbalance often reported in CKD patients.
Keywords	NAD(P)H oxidase (H2O2-forming) ; acetylcysteine ; adipocytes ; alpha-tocopherol ; culture media ; fluorescent dyes ; glutathione ; kidney diseases ; lipid peroxidation ; malondialdehyde ; mice ; oxidative stress ; oxygen ; renal function ; toxins ; white adipose tissue
Language	English
Dates of publication	2021-10
Size	p. 137-143.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	120345-9
ISSN	0300-9084
ISSN	0300-9084
DOI	10.1016/j.biochi.2021.06.020
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Inhibition of intestinal FXR activity as a possible mechanism for the beneficial effects of a probiotic mix supplementation on lipid metabolism alterations and weight gain in mice fed a high fat diet.

Beau, Alice / Benoit, Bérengère / Le Barz, Mélanie / Meugnier, Emmanuelle / Penhoat, Armelle / Calzada, Catherine / Pinteur, Claudie / Loizon, Emmanuelle / Chanon, Stéphanie / Vieille-Marchiset, Aurélie / Sauvinet, Valérie / Godet, Murielle / Laugerette, Fabienne / Holowacz, Sophie / Jacouton, Elsa / Michalski, Marie-Caroline / Vidal, Hubert

Gut microbes

2023 Volume 15, Issue 2, Page(s) 2281015

Abstract: Supplementation with probiotics has emerged as a promising therapeutic tool to manage metabolic diseases. We investigated the effects of a mix ... ...

Abstract	Supplementation with probiotics has emerged as a promising therapeutic tool to manage metabolic diseases. We investigated the effects of a mix of
MeSH term(s)	Mice ; Animals ; Diet, High-Fat/adverse effects ; Lipid Metabolism ; Gastrointestinal Microbiome ; Weight Gain ; Probiotics/pharmacology ; Probiotics/therapeutic use ; Liver/metabolism ; Triglycerides ; RNA, Messenger/metabolism ; RNA, Messenger/pharmacology ; Mice, Inbred C57BL ; Bile Acids and Salts/metabolism
Chemical Substances	Triglycerides ; RNA, Messenger ; Bile Acids and Salts
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2575755-6
ISSN	1949-0984 ; 1949-0984
ISSN (online)	1949-0984
ISSN	1949-0984
DOI	10.1080/19490976.2023.2281015
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Article ; Online: A low aromatic amino-acid diet improves renal function and prevent kidney fibrosis in mice with chronic kidney disease.

Barba, Christophe / Benoit, Bérengère / Bres, Emilie / Chanon, Stéphanie / Vieille-Marchiset, Aurélie / Pinteur, Claudie / Pesenti, Sandra / Glorieux, Griet / Picard, Cécile / Fouque, Denis / Soulage, Christophe O / Koppe, Laetitia

Scientific reports

2021 Volume 11, Issue 1, Page(s) 19184

Abstract: Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), their mechanisms of action are unclear. A reduced production of uremic toxins could contribute to the benefits of LPDs. Aromatic amino-acids (AA) are ... ...

Abstract	Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), their mechanisms of action are unclear. A reduced production of uremic toxins could contribute to the benefits of LPDs. Aromatic amino-acids (AA) are precursors of major uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS). We hypothesize that a low aromatic amino acid diet (LA-AAD, namely a low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the decreased production of uremic toxins. Kidney failure was chemically induced in mice with a diet containing 0.25% (w/w) of adenine. Mice received three different diets for six weeks: normoproteic diet (NPD: 14.7% proteins, aromatic AAs 0.019%), LPD (5% proteins, aromatic AAs 0.007%) and LA-AAD (14% proteins, aromatic AAs 0.007%). Both LPD and LA-AAD significantly reduced proteinuria, kidney fibrosis and inflammation. While LPD only slightly decreased plasma free PCS and free IS compared to NPD; free fractions of both compounds were significantly decreased by LA-AAD. These results suggest that a LA-AAD confers similar benefits of a LPD in delaying the progression of CKD through a reduction in some key uremic toxins production (such as PCS and IS), with a lower risk of malnutrition.
MeSH term(s)	Amino Acids, Aromatic/adverse effects ; Animals ; Diet, Protein-Restricted/adverse effects ; Diet, Protein-Restricted/methods ; Disease Models, Animal ; Fibrosis ; Humans ; Kidney/pathology ; Male ; Malnutrition/etiology ; Malnutrition/prevention & control ; Mice ; Renal Insufficiency, Chronic/diet therapy ; Renal Insufficiency, Chronic/pathology ; Uremic Toxins/metabolism
Chemical Substances	Amino Acids, Aromatic ; Uremic Toxins
Language	English
Publishing date	2021-09-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-98718-x
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Article ; Online: Fibroblast growth factor 19 as a countermeasure to muscle and locomotion dysfunctions in experimental cerebral palsy.

Pereira, Sabrina da Conceição / Benoit, Bérengère / de Aguiar Junior, Francisco Carlos Amanajás / Chanon, Stéphanie / Vieille-Marchiset, Aurélie / Pesenti, Sandra / Ruzzin, Jérome / Vidal, Hubert / Toscano, Ana Elisa

Journal of cachexia, sarcopenia and muscle

2021 Volume 12, Issue 6, Page(s) 2122–2133

Abstract: Background: Cerebral palsy (CP) associates cerebral function damages with strong locomotor defects and premature sarcopenia. We previously showed that fibroblast growth factor 19 (FGF19) exerts hypertrophic effects on skeletal muscle and improves muscle ...

Abstract	Background: Cerebral palsy (CP) associates cerebral function damages with strong locomotor defects and premature sarcopenia. We previously showed that fibroblast growth factor 19 (FGF19) exerts hypertrophic effects on skeletal muscle and improves muscle mass and strength in mouse models with muscle atrophy. Facing the lack of therapeutics to treat locomotor dysfunctions in CP, we investigated whether FGF19 treatment could have beneficial effects in an experimental rat model of CP. Methods: Cerebral palsy was induced in male Wistar rat pups by perinatal anoxia immediately after birth and by sensorimotor restriction of hind paws maintained until Day 28. Daily subcutaneous injections with recombinant human FGF19 (0.1 mg/kg bw) were performed from Days 22 to 28. Locomotor activity and muscle strength were assessed before and after FGF19 treatment. At Day 29, motor coordination on rotarod and various musculoskeletal parameters (weight of tibia bone and of soleus and extensor digitorum longus (EDL) muscles; area of skeletal muscle fibres) were evaluated. In addition, expression of specific genes linked to human CP was measured in rat skeletal muscles. Results: Compared to controls, CP rats had reduced locomotion activity (-37.8% of distance travelled, P < 0.05), motor coordination (-88.9% latency of falls on rotarod, P < 0.05) and muscle strength (-25.1%, P < 0.05). These defects were associated with reduction in soleus (-51.5%, P < 0.05) and EDL (-42.5%, P < 0.05) weight, smaller area of muscle fibres, and with lower tibia weight (-38%, P < 0.05). In muscles from rats submitted to CP, changes in the expression levels of several genes related to muscle development and neuromuscular junctions were similar to those found in wrist muscle of children with CP (increased mRNA levels of Igfbp5, Kcnn3, Gdf8, and MyH4 and decreased expression of Myog, Ucp2 and Lpl). Compared with vehicle-treated CP rats, FGF19 administration improved locomotor activity (+53.2%, P < 0.05) and muscle strength (+25.7%, P < 0.05), and increased tibia weight (+13.8%, P < 0.05) and soleus and EDL muscle weight (+28.6% and +27.3%, respectively, P < 0.05). In addition, it reduced a number of very small fibres in both muscles (P < 0.05). Finally, gene expression analyses revealed that FGF19 might counteract the immature state of skeletal muscles induced by CP. Conclusions: These results demonstrate that pharmacological intervention with recombinant FGF19 could restore musculoskeletal and locomotor dysfunction in an experimental CP model, suggesting that FGF19 may represent a potential therapeutic strategy to combat the locomotor disorders associated with CP.
MeSH term(s)	Animals ; Cerebral Palsy/drug therapy ; Female ; Fibroblast Growth Factors ; Locomotion ; Male ; Mice ; Muscle, Skeletal ; Pregnancy ; Rats ; Rats, Wistar ; Small-Conductance Calcium-Activated Potassium Channels
Chemical Substances	Kcnn3 protein, mouse ; Small-Conductance Calcium-Activated Potassium Channels ; Fibroblast Growth Factors (62031-54-3)
Language	English
Publishing date	2021-10-26
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2586864-0
ISSN	2190-6009 ; 2190-5991
ISSN (online)	2190-6009
ISSN	2190-5991
DOI	10.1002/jcsm.12819
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Article ; Online: The protein-bound uremic toxin p-cresyl-sulfate promotes intracellular ROS production and lipid peroxidation in 3T3-L1 adipose cells.

Koppe, Laetitia / Croze, Marine L / Monteiro, Elisa B / Benoit, Bérengère / Bres, Emilie / Guebre-Egziabher, Fitsum / Daleprane, Julio B / Fouque, Denis / Soulage, Christophe O

Biochimie

2021 Volume 189, Page(s) 137–143

Abstract	Patients with chronic kidney disease (CKD) often exhibit increased level of oxidative stress that contribute to the deterioration of renal function and uremic complications. White adipose tissue (WAT) has been recognized as a major site of production of radical oxygen species (ROS) in the context of metabolic diseases. This study was designed to decipher whether the protein bound uremic toxin p-cresyl-sulfate (p-CS) could contribute to ROS production in WAT and promote oxidative stress. Mouse 3T3-L1 adipocytes were incubated for 2 h in culture medium containing 212 μM p-CS, a concentration chosen to mimic levels encountered in end stage renal disease patients or KCl as a control and intracellular ROS production was measured using the fluorescent probe 5-6-carboxy-2',7'-dichlorodihydrofluorescein diacetate. Oxidative insult was estimated by the measurement of malondialdehyde (MDA) content and glutathione content. The effects of probenecid (1 mM) a potent inhibitor of organic anion transporter, apocynin (1 mM) an inhibitor of NADPH oxidase or common antioxidants such as α-tocopherol (2.5 μM), ascorbate (200 μM), and N-acetylcysteine (500 μM) were further evaluated. p-CS triggered a striking increase in ROS production (+228%, p < 0.01), in MDA content (+214%, p < 0.005) and a decrease in glutathione (-47%, P < 0.01). Pre-treatment of cells with probenecid, apocynin or antioxidants prevented the p-CS induced ROS production and oxidative insults. These results suggest that in uremic state, the intracellular accumulation of p-CS in adipose cells could contribute, through an activation of NADPH oxidase, to the redox imbalance often reported in CKD patients.
MeSH term(s)	3T3-L1 Cells ; Adipocytes/metabolism ; Animals ; Cresols/pharmacology ; Lipid Peroxidation/drug effects ; Mice ; Oxidative Stress/drug effects ; Reactive Oxygen Species/metabolism ; Renal Insufficiency, Chronic/metabolism ; Sulfuric Acid Esters/pharmacology
Chemical Substances	Cresols ; Reactive Oxygen Species ; Sulfuric Acid Esters ; 4-cresol sulfate (56M34ZQY1S)
Language	English
Publishing date	2021-07-02
Publishing country	France
Document type	Journal Article
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2021.06.020
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Article ; Online: Saturated and Unsaturated Fatty Acids Differently Modulate Colonic Goblet Cells In Vitro and in Rat Pups.

Benoit, Bérengère / Bruno, Jérémie / Kayal, Fanny / Estienne, Monique / Debard, Cyrille / Ducroc, Robert / Plaisancié, Pascale

The Journal of nutrition

2015 Volume 145, Issue 8, Page(s) 1754–1762

Abstract: Background: High-fat diets induce intestinal barrier alterations and promote intestinal diseases. Little is known about the effects of long-chain fatty acids (LCFAs) on mucin 2 (MUC2) production by goblet cells, which are crucial for intestinal ... ...

Abstract	Background: High-fat diets induce intestinal barrier alterations and promote intestinal diseases. Little is known about the effects of long-chain fatty acids (LCFAs) on mucin 2 (MUC2) production by goblet cells, which are crucial for intestinal protection. Objective: We investigated the effects of LCFAs on the differentiation of colonic goblet cells, MUC2 expression, and colonic barrier function. Methods: Upon reaching confluence, human colonic mucus-secreting HT29-MTX cells were stimulated (21 d) with a saturated LCFA (palmitic or stearic acid), a monounsaturated LCFA (oleic acid), or a polyunsaturated LCFA (linoleic, γ-linolenic, α-linolenic, or eicosapentaenoic acid). In addition, rat pups underwent oral administration of oil (palm, rapeseed, or sunflower oil) or water (10 μL/g body weight, postnatal days 10-15). Subsequently, colon goblet cells were studied by Western blotting, reverse transcriptase-quantitative polymerase chain reaction, and immunohistochemistry and colonic transmucosal electrical resistance was measured by using Ussing chambers. Results: In vitro, palmitic acid enhanced MUC2 production (140% of control) and hepatocyte nuclear factor 4α expression, whereas oleic, linoleic, γ-linolenic, α-linolenic, and eicosapentaenoic acids reduced MUC2 expression (at least -50% of control). All unsaturated LCFAs decreased the expression of human atonal homolog 1, a transcription factor controlling goblet cell differentiation (at least -31% vs. control). In vivo, rats fed palm oil had higher palmitic acid concentrations (3-fold) in their colonic contents and increased mucus granule surfaces in their goblet cells (>2-fold) than did all other groups. Palm oil also increased colonic transmucosal electrical resistance (245% of control), yet had no effect on occludin and zonula occludens-1 expression. In contrast, sunflower and rapeseed oils decreased goblet cell number when compared with control (at least -10%) and palm oil (at least -14%) groups. Conclusions: Palm oil in rat pups and palmitic acid in HT29-MTX cells increase the production of MUC2 and strengthen the intestinal barrier. In contrast, unsaturated LCFAs decrease MUC2 expression. These data should be taken into account in the context of preventive or therapeutic nutritional programs.
MeSH term(s)	Animal Feed/analysis ; Animals ; Colon/cytology ; Diet ; Dietary Fats/administration & dosage ; Dietary Fats/pharmacology ; Fatty Acids/administration & dosage ; Fatty Acids/pharmacology ; Fatty Acids, Unsaturated/administration & dosage ; Fatty Acids, Unsaturated/pharmacology ; Goblet Cells/drug effects ; Goblet Cells/metabolism ; HT29 Cells ; Humans ; Mucin 5AC/genetics ; Mucin 5AC/metabolism ; Mucin-2/genetics ; Mucin-2/metabolism ; Plant Oils/administration & dosage ; Plant Oils/chemistry ; Rats ; Rats, Wistar
Chemical Substances	Dietary Fats ; Fatty Acids ; Fatty Acids, Unsaturated ; MUC2 protein, human ; MUC5AC protein, human ; Mucin 5AC ; Mucin-2 ; Plant Oils
Language	English
Publishing date	2015-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.3945/jn.115.211441
Database	MEDical Literature Analysis and Retrieval System OnLINE

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