Methionine sulfoxide reductase A deficiency exacerbates progression of kidney fibrosis induced by unilateral ureteral obstruction

2015 ◽  
Vol 89 ◽  
pp. 201-208 ◽  
Author(s):  
Jee In Kim ◽  
Mi Ra Noh ◽  
Ki Young Kim ◽  
Hee-Seong Jang ◽  
Hwa-Young Kim ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Methionine Sulfoxide ◽  
Unilateral Ureteral Obstruction ◽  
Methionine Sulfoxide Reductase ◽  
Kidney Fibrosis ◽  
Methionine Sulfoxide Reductase A

scholarly journals An unusual thioredoxin system in the facultative parasite Acanthamoeba castellanii

2021 ◽  
Vol 78 (7) ◽  
pp. 3673-3689
Author(s):  
David Leitsch ◽  
Alvie Loufouma Mbouaka ◽  
Martina Köhsler ◽  
Norbert Müller ◽  
Julia Walochnik
Keyword(s):  
Oxidative Stress ◽  
Stop Codon ◽  
Acanthamoeba Castellanii ◽  
Methionine Sulfoxide ◽  
Redox System ◽  
Methionine Sulfoxide Reductase ◽  
Methionine Sulfoxide Reductase A ◽  
Protein Levels ◽  
Thioredoxin System ◽  
Facultative Parasite

AbstractThe free-living amoeba Acanthamoeba castellanii occurs worldwide in soil and water and feeds on bacteria and other microorganisms. It is, however, also a facultative parasite and can cause serious infections in humans. The annotated genome of A. castellanii (strain Neff) suggests the presence of two different thioredoxin reductases (TrxR), of which one is of the small bacterial type and the other of the large vertebrate type. This combination is highly unusual. Similar to vertebrate TrxRases, the gene coding for the large TrxR in A. castellanii contains a UGA stop codon at the C-terminal active site, suggesting the presence of selenocysteine. We characterized the thioredoxin system in A. castellanii in conjunction with glutathione reductase (GR), to obtain a more complete understanding of the redox system in A. castellanii and the roles of its components in the response to oxidative stress. Both TrxRases localize to the cytoplasm, whereas GR localizes to the cytoplasm and the large organelle fraction. We could only identify one thioredoxin (Trx-1) to be indeed reduced by one of the TrxRases, i.e., by the small TrxR. This thioredoxin, in turn, could reduce one of the two peroxiredoxins tested and also methionine sulfoxide reductase A (MsrA). Upon exposure to hydrogen peroxide and diamide, only the small TrxR was upregulated in expression at the mRNA and protein levels, but not the large TrxR. Our results show that the small TrxR is involved in the A. castellanii’s response to oxidative stress. The role of the large TrxR, however, remains elusive.

scholarly journals Matrix Metalloproteinase-2 Knockout and Heterozygote Mice Are Protected from Hydronephrosis and Kidney Fibrosis after Unilateral Ureteral Obstruction

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0143390 ◽  
Author(s):  
Maria K. Tveitarås ◽  
Trude Skogstrand ◽  
Sabine Leh ◽  
Frank Helle ◽  
Bjarne M. Iversen ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Ureteral Obstruction ◽  
Unilateral Ureteral Obstruction ◽  
Matrix Metalloproteinase 2 ◽  
Kidney Fibrosis

Fate alteration of bone marrow-derived macrophages ameliorates kidney fibrosis in murine model of unilateral ureteral obstruction

2018 ◽  
Vol 34 (10) ◽  
pp. 1657-1668 ◽  
Author(s):  
Ying Yang ◽  
Xiaojian Feng ◽  
Xinyan Liu ◽  
Ying Wang ◽  
Min Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Unilateral Ureteral Obstruction ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pathological Feature ◽  
Kidney Fibrosis ◽  
Anti Inflammatory

AbstractBackgroundRenal fibrosis is a key pathological feature and final common pathway leading to end-stage kidney failure in many chronic kidney diseases. Myofibroblast is the master player in renal fibrosis. However, myofibroblasts are heterogeneous. Recent studies show that bone marrow-derived macrophages transform into myofibroblasts by transforming growth factor (TGF)-β-induced macrophage–myofibroblast transition (MMT) in renal fibrosis.MethodsTGF-β signaling was redirected by inhibition of β-catenin/T-cell factor (TCF) to increase β-catenin/Foxo in bone marrow-derived macrophages. A kidney fibrosis model of unilateral ureteral obstruction was performed in EGFP bone marrow chimera mouse. MMT was examined by flow cytometry analysis of GFP+F4/80+α-SMA+ cells from unilateral ureteral obstruction (UUO) kidney, and by immunofluorescent staining of bone marrow-derived macrophages in vitro. Inflammatory and anti-inflammatory cytokines were analysis by enzyme-linked immunosorbent assay.ResultsInhibition of β-catenin/TCF by ICG-001 combined with TGF-β1 treatment increased β-catenin/Foxo1, reduced the MMT and inflammatory cytokine production by bone marrow-derived macrophages, and thereby, reduced kidney fibrosis in the UUO model.ConclusionsOur results demonstrate that diversion of β-catenin from TCF to Foxo1-mediated transcription not only inhibits the β-catenin/TCF-mediated fibrotic effect of TGF-β, but also enhances its anti-inflammatory action, allowing therapeutic use of TGF-β to reduce both inflammation and fibrosis at least partially by changing the fate of bone marrow-derived macrophages.

scholarly journals METABOLIC CONSEQUENCES OF METHIONINE REDOX IN METHIONINE RESTRICTION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S106-S107
Author(s):  
Kevin Thyne ◽  
Yuhong Liu ◽  
Adam B Salmon
Keyword(s):  
Protein Function ◽  
Methionine Sulfoxide ◽  
Redox Status ◽  
Significant Loss ◽  
Methionine Sulfoxide Reductase ◽  
Wild Type ◽  
Entire Family ◽  
Methionine Sulfoxide Reductase A ◽  
Methionine Restriction

Abstract While caloric restriction (CR) provides highly robust improvements to longevity and health, dietary restriction of the essential amino acid methionine can provide similar benefits including improved metabolic function and increased longevity. Despite these similarities between CR and methionine restriction (MR), there is growing evidence to suggest they may be mediated by different mechanisms that require further elucidation. The sulfur side-chain of methionine is highly prone to oxidation, even in vivo, with redox changes of these residues potentially altering protein function and interfering with its use as a substrate. An entire family of enzymes, methionine sulfoxide reductases, have evolved in aerobic organisms to regulate the redox status of methionine. We tested the role of methionine sulfoxide reductase A (MsrA) in the physiological and metabolic benefits of MR. After three months of MR, mice lacking MsrA (MsrA KO) showed significant loss of weight, including both fat and lean mass, in comparison to wild-type mice under MR. Both MsrA KO and wild-type mice responded to MR with improvements to both glucose and insulin tolerance. However, MR MsrA KO mice showed lower HbA1c and reduced leptin compared to MR wild-type mice. Overall, our results show mice lacking MsrA have a stronger response to MR suggesting that methionine redox may play an important role in some of the mechanisms responsible for these metabolic outcomes. Further studies clarify whether MsrA could also be a potential regulator of the longevity benefits of MR.

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