scholarly journals Decreased ZO1 expression causes loss of time-dependent tight junction function in the liver of ob/ob mice

2021 ◽  
Author(s):  
Yuya Tsurudome ◽  
Nao Morita ◽  
Michiko Horiguchi ◽  
Kentaro Ushijima
Keyword(s):  
Tight Junction ◽  
Dark Period ◽  
Vital Role ◽  
Time Dependent ◽  
Signal Transduction System ◽  
Binding Ability ◽  
Protein Levels ◽  
Multiple Organs ◽  
Zonula Occludens ◽  
Zonula Occludens 1

Abstract Diabetes patients are at a high risk of developing complications related to angiopathy and disruption of the signal transduction system. The liver is one of the multiple organs damaged during diabetes. Few studies have evaluated the morphological effects of adhesion factors in diabetic liver. The influence of diurnal variation has been observed in the expression and functioning of adhesion molecules to maintain tissue homeostasis associated with nutrient uptake. The present study demonstrated that the rhythm-influenced functioning of tight junction was impaired in the liver of ob/ob mice. The tight junctions of hepatocytes were loosened during the dark period in normal mice compared to those in ob/ob mice, where the hepatocyte gaps remained open throughout the day. The time-dependent expression of zonula occludens 1 (ZO1) in the liver plays a vital role in the functioning of the tight junction. The time-dependent expression of ZO1 was nullified and its expression was attenuated in the liver of ob/ob mice. ZO1 expression was inhibited at the mRNA and protein levels. The expression rhythm of ZO1 was found to be regulated by heat shock factor (HSF)1/2, the expression of which was reduced in the liver of ob/ob mice. The DNA-binding ability of HSF1/2 was decreased in the liver of ob/ob mice compared to that in normal mice. These findings suggest the involvement of impaired expression and functioning of adhesion factors in diabetic liver complications.

scholarly journals Busulfan administration produces toxic effects on epididymal morphology and inhibits the expression of ZO-1 and vimentin in the mouse epididymis

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Fang Fang ◽  
Ke Ni ◽  
Yiting Cai ◽  
Qian Zhao ◽  
Jin Shang ◽  
...  
Keyword(s):  
Single Injection ◽  
Morphological Structure ◽  
Estrogen Receptor Α ◽  
Structure And Function ◽  
Testicular Damage ◽  
Protein Levels ◽  
Zonula Occludens ◽  
Zonula Occludens 1 ◽  
And Function ◽  
Mouse Epididymis

Busulfan is an alkane sulphonate currently used as an anticancer drug and to prepare azoospermic animal models, because it selectively destroys differentiated spermatogonia in the testes. However, few studies have focussed on the exact effects of busulfan treatment on the epididymis currently. The present study assessed the effect of busulfan on epididymal morphology and the blood–epididymis barrier in mice. We treated mice with a single injection of busulfan and detected the effect at different time points. We showed that busulfan was toxic to the morphological structure and function of the epididymis. Furthermore, busulfan treatment down-regulated the epididymal expression of vimentin and zonula occludens-1 (ZO-1) at the mRNA and protein levels. In addition, there was an increase in total androgen receptor (AR) levels, whereas the estrogen receptor-α (ER-α) levels were reduced, both in the caput and cauda regions after busulfan treatment, which may be secondary to the testicular damage. In conclusion, our study describes the effects of busulfan administration on the mouse epididymis and also provides a potential understanding of male infertility arising from chemotherapy-related defects in the epididymis.

scholarly journals High dose of baicalin or baicalein can reduce tight junction integrity by partly targeting the first PDZ domain of zonula occludens-1 (ZO-1)

2020 ◽  
Vol 887 ◽  
pp. 173436 ◽  
Author(s):  
Misaki Hisada ◽  
Minami Hiranuma ◽  
Mio Nakashima ◽  
Natsuko Goda ◽  
Takeshi Tenno ◽  
...  
Keyword(s):  
Tight Junction ◽  
Pdz Domain ◽  
High Dose ◽  
Zonula Occludens ◽  
Zonula Occludens 1

scholarly journals High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6

2019 ◽  
Vol 317 (6) ◽  
pp. F1605-F1611 ◽  
Author(s):  
Xiao-Yu Lu ◽  
Bing-Chen Liu ◽  
Yu-Ze Cao ◽  
Chang Song ◽  
Hua Su ◽  
...  
Keyword(s):  
High Glucose ◽  
Transient Receptor Potential ◽  
Morphological Changes ◽  
Receptor Potential ◽  
Diabetic Rat ◽  
Protein Levels ◽  
Zonula Occludens ◽  
Junction Protein ◽  
Zonula Occludens 1 ◽  
Transient Receptor

The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function. Gain of TRPC6 function and loss of podocin function induce podocyte injury. We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown. Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose. High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys. The decreased podocin was diminished in TRPC6 knockdown podocytes. High glucose elevated intracellular Ca2+ in control podocytes but not in TRPC6 knockdown podocytes. High glucose also elevated the expression of a tight junction protein, zonula occludens-1, and induced the redistribution of zonula occludens-1 and loss of podocyte processes. These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.

scholarly journals Spatial Overlap of Claudin- and Phosphatidylinositol Phosphate-Binding Sites on the First PDZ Domain of Zonula Occludens 1 Studied by NMR

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2465 ◽  
Author(s):  
Hidekazu Hiroaki ◽  
Kaori Satomura ◽  
Natsuko Goda ◽  
Yukako Nakakura ◽  
Minami Hiranuma ◽  
...  
Keyword(s):  
Tight Junction ◽  
Binding Site ◽  
Solution Structure ◽  
Pdz Domain ◽  
Molecular Surface ◽  
Head Group ◽  
Functional Domain ◽  
Phosphate Binding ◽  
Zonula Occludens ◽  
Zonula Occludens 1

Background: The tight junction is an intercellular adhesion complex composed of claudins (CLDs), occludin, and the scaffolding proteins zonula occludens 1 (ZO-1) and its two paralogs ZO-2 and ZO-3. ZO-1 is a multifunctional protein that contains three PSD95/Discs large/ZO-1(PDZ) domains. A key functional domain of ZO-1 is the first PDZ domain (ZO-1(PDZ1)) that recognizes the conserved C-termini of CLDs. Methods: In this study, we confirmed that phosphoinositides bound directly to ZO-1(PDZ1) by biochemical and solution NMR experiments. We further determined the solution structure of mouse ZO-1(PDZ1) by NMR and mapped the phosphoinositide binding site onto its molecular surface. Results: The phosphoinositide binding site was spatially overlapped with the CLD-binding site of ZO-1(PDZ1). Accordingly, inositol-hexaphosphate (phytic acid), an analog of the phosphoinositide head group, competed with ZO-1(PDZ)-CLD interaction. Conclusions: The results suggested that the PDZ domain–phosphoinositide interaction plays a regulatory role in biogenesis and homeostasis of the tight junction.

Copper treatment alters the permeability of tight junctions in cultured human intestinal Caco-2 cells

1999 ◽  
Vol 277 (6) ◽  
pp. G1138-G1148 ◽  
Author(s):  
Simonetta Ferruzza ◽  
Maria-Laura Scarino ◽  
Giuseppe Rotilio ◽  
Maria Rosa Ciriolo ◽  
Paolo Santaroni ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Electrical Resistance ◽  
Transepithelial Electrical Resistance ◽  
Complete Medium ◽  
Zonula Occludens ◽  
Intracellular Effect ◽  
Tight Junction Permeability ◽  
Zonula Occludens 1 ◽  
Effect Of Copper

The effects of copper on tight-junction permeability were investigated in human intestinal Caco-2 cells, monitoring transepithelial electrical resistance and transepithelial passage of mannitol. Apical treatment of Caco-2 cells with 10–100 μM CuCl2(up to 3 h) produced a time- and concentration-dependent increase in tight-junction permeability, reversible after 24 h in complete medium in the absence of added copper. These effects were not observed in cells treated with copper complexed to l-histidine [Cu(His)2]. The copper-induced increase in tight-junction permeability was affected by the pH of the apical medium, as was the apical uptake of64CuCl2, both exhibiting a maximum at pH 6.0. Treatment with CuCl2produced a concentration-dependent reduction in the staining of F actin but not of the junctional proteins zonula occludens-1, occludin, and E-cadherin and produced ultrastructural alterations to microvilli and tight junctions that were not observed after treatment with up to 200 μM Cu(His)2for 3 h. Overall, these data point to an intracellular effect of copper on tight junctions, mediated by perturbations of the F actin cytoskeleton.

scholarly journals Effects of emodin on intestinal mucosal barrier by the upregulation of miR-218a-5p expression in rats with acute necrotizing pancreatitis

2020 ◽  
Vol 34 ◽  
pp. 205873842094176
Author(s):  
Yang Tan ◽  
Wei Zhang ◽  
Hai-ying Wu ◽  
Jing Xia ◽  
Huang-bo Zhang ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Intestinal Tract ◽  
Caspase 3 ◽  
Intestinal Cell ◽  
Caspase 9 ◽  
Acute Severe Pancreatitis ◽  
Protein Levels ◽  
Zonula Occludens ◽  
Severe Pancreatitis ◽  
Zonula Occludens 1

Emodin is an effective component in rhubarb to cure intestinal dysfunction, but the specific mechanism remains unknown. This study aimed to evaluate the protective effects of emodin on intestinal dysfunction caused by acute severe pancreatitis and reveal the functional mechanism of emodin in the treatment of this condition. An acute severe pancreatitis model was prepared using taurocholate. In the treatment group, 50 mg/kg emodin was injected intravenously 2 h before the induction of acute severe pancreatitis at an interval of 8 h. After 24 h, the gene expression and protein levels of miR-218a-5p, RhoA, ROCK1, Akt, Notch1, Bax, Bcl-2, Fas, FasL, caspase-3, and caspase-9 were determined through reverse transcription polymerase chain reaction and Western blot analysis. The protein levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract were also determined through Western blot analysis. The effects of miR-218a-5p on the apoptosis of rat intestinal epithelial cell-18 were observed through flow cytometry. The effects of emodin on intestinal cell apoptosis induced by acute severe pancreatitis were observed via TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Pathological changes in the pancreas and intestine of rats in each group were observed through hematoxylin and eosin staining. After 24 h of acute severe pancreatitis induced by taurocholate, emodin reduced the expression of miR-218a-5p in the intestinal tract; increased the expression of Notch1 and Bcl-2; decreased the expression levels of RhoA, ROCK1, Akt, Bax, Fas, FasL, caspase-3, and caspase-9; inhibited the intestinal cell apoptosis caused by acute severe pancreatitis; increased the protein expression levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract; and alleviated intestinal dysfunction caused by acute severe pancreatitis. Emodin could regulate Notch1 and RhoA/ROCK pathways by regulating the miR-218a-5p expression in the intestine. It could also inhibit intestinal cell apoptosis induced by acute severe pancreatitis and improve the intestinal dysfunction caused by severe acute pancreatitis.

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