scholarly journals Localization of Thioredoxin-interacting Protein (TXNIP) mRNA in Epithelium of Human Gastrointestinal Tract

2003 ◽  
Vol 51 (7) ◽  
pp. 973-976 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yukimoto Ishii ◽  
Akiko Murata ◽  
Toshihito Nagata ◽  
Satoshi Asai

Thioredoxin-interacting protein (TXNIP) is a negative regulator of thioredoxin. However, its role in the gastrointestinal (GI) epithelium is as yet unknown. Using in situ hybridization, we demonstrated that mRNA of TXNIP was differentially expressed in the epithelium of the human GI tract. TXNIP transcript was especially prominent in terminal differentiated cells. TXNIP was also highly expressed in lymphocytes in the lymphoid follicles. Our results suggest a new potential role of TXNIP in the differentiation of epithelial cells and in mucosal immunity of the GI tract.

2021 ◽  
Vol 22 (5) ◽  
pp. 2754
Author(s):  
Naila Qayyum ◽  
Muhammad Haseeb ◽  
Moon Suk Kim ◽  
Sangdun Choi

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.


2010 ◽  
Vol 25 (7) ◽  
pp. 2141-2149 ◽  
Author(s):  
T. Zitman-Gal ◽  
J. Green ◽  
M. Pasmanik-Chor ◽  
V. Oron-Karni ◽  
J. Bernheim

2000 ◽  
Vol 11 (9) ◽  
pp. 2987-2998 ◽  
Author(s):  
Kelly P. Smith ◽  
Jeanne Bentley Lawrence

The Cajal (coiled) body (CB) is a structure enriched in proteins involved in mRNA, rRNA, and snRNA metabolism. CBs have been shown to interact with specific histone and snRNA gene loci. To examine the potential role of CBs in U2 snRNA metabolism, we used a variety of genomic and oligonucleotide probes to visualize in situ newly synthesized U2 snRNA relative to U2 loci and CBs. Results demonstrate that long spacer sequences between U2 coding repeats are transcribed, supporting other recent evidence that U2 transcription proceeds past the 3′ box. The presence of bright foci of this U2 locus RNA differed between alleles within the same nucleus; however, this did not correlate with the loci's association with a CB. Experiments with specific oligonucleotide probes revealed signal for preU2 RNA within CBs. PreU2 was also detected in the locus-associated RNA foci, whereas sequences 3′ of preU2 were found only in these foci, not in CBs. This suggests that a longer primary transcript is processed before entry into CBs. Although this work shows that direct contact of a U2 locus with a CB is not simply correlated with RNA at that locus, it provides the first evidence of new preU2 transcripts within CBs. We also show that, in contrast to CBs, SMN gems do not associate with U2 gene loci and do not contain preU2. Because other evidence indicates that preU2 is processed in the cytoplasm before assembly into snRNPs, results point to an involvement of CBs in modification or transport of preU2 RNA.


2018 ◽  
Vol 10 (2) ◽  
pp. 106-118 ◽  
Author(s):  
Yoko Ito ◽  
Niccolette Schaefer ◽  
Amelia Sanchez ◽  
David Francisco ◽  
Rafeul Alam ◽  
...  

Toll-interacting protein (Tollip) is a key negative regulator of innate immunity by preventing excessive proinflammatory responses. Tollip genetic variation has been associated with airflow limitation in asthma subjects and Tollip expression. Whether Tollip regulates lung inflammation in a type 2 cytokine milieu (e.g., IL-13) is unclear. Our goal was to determine the in vivo role of Tollip in IL-13-mediated lung eosinophilic inflammation and the underlying mechanisms. Tollip-knockout (KO) and wild-type (WT) mice were inoculated intranasally with recombinant mouse IL-13 protein to examine lung inflammation. To determine how Tollip regulates inflammation, alveolar macrophages and bone marrow-derived macrophages from Tollip KO and WT mice were cultured with or without IL-13 and/or IL-33. IL-13-treated Tollip KO mice significantly increased lung eosinophilic inflammation and eotaxin-2 (CCL24) levels compared with the WT mice. IL-13- treated Tollip KO (vs. WT) macrophages, in the absence and particularly in the presence of IL-33, increased expression of the IL-33 receptor ST2L and CCL24, which was in part dependent on enhanced activation of interleukin (IL)-1 receptor-associated kinase 1 (IRAK1) and signal transducer and activator of transcription 6 (STAT6). Our results suggest that Tollip downregulates IL-13-mediated pulmonary eosinophilia in part through inhibiting the activity of the ST2L/IL-33/IRAK1 axis and STAT6.


2019 ◽  
Author(s):  
Rui Ding ◽  
ZhengTao Gu ◽  
ChangSheng Yang ◽  
CaiQiang Huang ◽  
QingChu Li ◽  
...  

Abstract BackgroundLong non-coding RNAs (LncRNAs) have been found to regulate innumerable diseases, yet the role of lncRNA MEG3 in osteoporosis (OP) has rarely been discussed. Here, we intend to probe into the mechanism of MEG3 on OP development by modulating microRNA-214 (miR-214) and thioredoxin-interacting protein (TXNIP)MethodsRat models of OP were established. MEG3, miR-214, and TXNIP mRNA expression in rat femoral tissues was detected, along with TXNIP, PCNA, cyclin D1, OCN, RUNX2, Osteolix, OPG, and PANKL protein expression. Ca, P and ALP contents in rat blood samples were also determined. Primary osteoblasts were isolated and cultured. Viability, COL-I, COL-II and COL-Χ contents, ALP content and activity, and mineralized nodule area of rat osteoblasts in each group were further detected.ResultsMEG3 and TXNIP were overexpressed while miR-214 was underexpressed in femoral tissues of OP rats. MEG3 silencing and miR-214 overexpression increased BMD, BV/TV, Tb.N, Tb.Th, the number of osteoblasts, collagen area and OPG expression, and downregulated PANKL of femoral tissues in OP rats. MEG3 silencing and miR-214 overexpression elevated Ca and P contents and reduced ALP content in OP rats’ blood, elevated viability, differentiation ability, COL-I and COL-Χ contents and ALP activity, and abated COL-II content of osteoblasts. MEG3 specifically bound to miR-214 to regulate TXNIP.ConclusionCollectively, we demonstrated that MEG3 silencing and miR-214 overexpression promote proliferation and differentiation of osteoblasts in OP by downregulating TXNIP, which further improves OP.


2008 ◽  
Vol 156 (1) ◽  
pp. 92-99.e2 ◽  
Author(s):  
Martin Landsberger ◽  
Alexander Staudt ◽  
Sangita Choudhury ◽  
Christiane Trimpert ◽  
Lars R. Herda ◽  
...  

2013 ◽  
Vol 305 (2) ◽  
pp. E263-E270 ◽  
Author(s):  
Sevasti Zervou ◽  
Tanmoy Ray ◽  
Natasha Sahgal ◽  
Liam Sebag-Montefiore ◽  
Rebecca Cross ◽  
...  

Creatine is important for energy metabolism, yet excitable cells such as cardiomyocytes do not synthesize creatine and rely on uptake via a specific membrane creatine transporter (CrT; SLC6A8). This process is tightly controlled with downregulation of CrT upon continued exposure to high creatine via mechanisms that are poorly understood. Our aim was to identify candidate endogenous CrT inhibitors. In 3T3 cells overexpressing the CrT, creatine uptake plateaued at 3 h in response to 5 mM creatine but peaked 33% higher ( P < 0.01) in the presence of cycloheximide, suggesting CrT regulation depends on new protein synthesis. Global gene expression analysis identified thioredoxin-interacting protein (Txnip) as the only significantly upregulated gene (by 46%) under these conditions ( P = 0.036), subsequently verified independently at mRNA and protein levels. There was no change in Txnip expression with exposure to 5 mM taurine, confirming a specific response to creatine rather than osmotic stress. Small-interfering RNA against Txnip prevented Txnip upregulation in response to high creatine, maintained normal levels of creatine uptake, and prevented downregulation of CrT mRNA. These findings were relevant to the in vivo heart since creatine-deficient mice showed 39.71% lower levels of Txnip mRNA, whereas mice overexpressing the CrT had 57.6% higher Txnip mRNA levels and 28.7% higher protein expression compared with wild types (mean myocardial creatine concentration 124 and 74 nmol/mg protein, respectively). In conclusion, we have identified Txnip as a novel negative regulator of creatine levels in vitro and in vivo, responsible for mediating substrate feedback inhibition and a potential target for modulating creatine homeostasis.


2019 ◽  
Author(s):  
Subhrangshu Mandal ◽  
Sabyasachi Bhattacharya ◽  
Chayan Roy ◽  
Moidu Jameela Rameez ◽  
Jagannath Sarkar ◽  
...  

ABSTRACTTo explore the potential role of tetrathionate in the sulfur cycle of marine sediments, the population ecology of tetrathionate-forming, oxidizing, and respiring microorganisms was revealed at 15-30 cm resolution along two, ∼3-m-long, cores collected from 530- and 580-mbsl water-depths of Arabian Sea, off India’s west coast, within the oxygen minimum zone (OMZ). Metagenome analysis along the two sediment-cores revealed widespread occurrence of the structural genes that govern these metabolisms; high diversity and relative-abundance was also detected for the bacteria known to render these processes. Slurry-incubation of the sediment-samples, pure-culture isolation, and metatranscriptome analysis, corroborated thein situfunctionality of all the three metabolic-types. Geochemical analyses revealed thiosulfate (0-11.1 μM), pyrite (0.05-1.09 wt %), iron (9232-17234 ppm) and manganese (71-172 ppm) along the two sediment-cores. Pyrites (via abiotic reaction with MnO2) and thiosulfate (via oxidation by chemolithotrophic bacteria prevalentin situ) are apparently the main sources of tetrathionate in this ecosystem. Tetrathionate, in turn, can be either converted to sulfate (via oxidation by the chemolithotrophs present) or reduced back to thiosulfate (via respiration by native bacteria); 0-2.01 mM sulfide present in the sediment-cores may also reduce tetrathionate abiotically to thiosulfate and elemental sulfur. Notably tetrathionate was not detectedin situ- high microbiological and geochemical reactivity of this polythionate is apparently instrumental in the cryptic nature of its potential role as a central sulfur cycle intermediate. Biogeochemical roles of this polythionate, albeit revealed here in the context of OMZ sediments, may well extend to the sulfur cycles of other geomicrobiologically-distinct marine sediment horizons.


2019 ◽  
Author(s):  
Subhrangshu Mandal ◽  
Sabyasachi Bhattacharya ◽  
Chayan Roy ◽  
Moidu Jameela Rameez ◽  
Jagannath Sarkar ◽  
...  

Abstract. To explore the potential role of tetrathionate in the sulfur cycle of marine sediments, the population ecology of tetrathionate-forming, oxidizing, and respiring microorganisms was revealed at 15–30 cm resolution along two, ~ 3-m-long, cores collected from 530- and 580-mbsl water-depths of Arabian Sea, off India’s west coast, within the oxygen minimum zone (OMZ). Metagenome analysis along the two sediment-cores revealed widespread occurrence of the structural genes that govern these metabolisms; high diversity and relative-abundance was also detected for the bacteria known to render these processes. Slurry-incubation of the sediment-samples, pure-culture isolation, and metatranscriptome analysis, corroborated the in situ functionality of all the three metabolic-types. Geochemical analyses revealed thiosulfate (0–11.1 µM), pyrite (0.05–1.09 wt %), iron (9232–17234 ppm) and manganese (71–172 ppm) along the two sediment-cores. Pyrites (via abiotic reaction with MnO2) and thiosulfate (via oxidation by chemolithotrophic bacteria prevalent in situ) are apparently the main sources of tetrathionate in this ecosystem. Tetrathionate, in turn, can be either converted to sulfate (via oxidation by the chemolithotrophs present) or reduced back to thiosulfate (via respiration by native bacteria); 0–2.01 mM sulfide present in the sediment-cores may also reduce tetrathionate abiotically to thiosulfate and elemental sulfur. Notably tetrathionate was not detected in situ – high microbiological and geochemical reactivity of this polythionate is apparently instrumental in the cryptic nature of its potential role as a central sulfur cycle intermediate. Biogeochemical roles of this polythionate, albeit revealed here in the context of OMZ sediments, may well extend to the sulfur cycles of other geomicrobiologically-distinct marine sediment horizons.


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