scholarly journals The Rab-Rabphilin system in injured human podocytes stressed by glucose overload and angiotensin II

2020 ◽  
Vol 319 (2) ◽  
pp. F178-F191 ◽  
Author(s):  
Olga Martinez-Arroyo ◽  
Ana Ortega ◽  
Javier Perez-Hernandez ◽  
Felipe J. Chaves ◽  
Josep Redon ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Expression Patterns ◽  
Mrna Level ◽  
Vesicular Transport ◽  
Kidney Injury ◽  
Rab Gtpases ◽  
Protein Levels ◽  
Differentiated Cells ◽  
Filtration Barrier ◽  
The Impact

Kidney injury in hypertension and diabetes entails, among in other structures, damage in a key cell of the glomerular filtration barrier, the podocyte. Podocytes are polarized and highly differentiated cells in which vesicular transport, partly driven by Rab GTPases, is a relevant process. The aim of the present study was to analyze Rab GTPases of the Rab-Rabphilin system in human immortalized podocytes and the impact of high glucose and angiotensin II. Furthermore, alterations of the system in urine cell pellets from patients with hypertension and diabetes were studied. Apoptosis was analyzed in podocytes, and mRNA level quantification, Western blot analysis, and immunofluorescence were developed to quantify podocyte-specific molecules and Rab-Rabphilin components (Rab3A, Rab27A, and Rabphilin3A). Quantitative RT-PCR was performed on urinary cell pellet from patients. The results showed that differentiated cells had reduced protein levels of the Rab-rabphillin system compared with undifferentiated cells. After glucose overload and angiotensin II treatment, apoptosis was increased and podocyte-specific proteins were reduced. Rab3A and Rab27A protein levels were increased under glucose overload, and Rabphilin3A decreased. Furthermore, this system exhibited higher levels under stress conditions in a manner of angiotensin II dose and time treatment. Immunofluorescence imaging indicated different expression patterns of podocyte markers and Rab27A under treatments. Finally, Rab3A and Rab27A were increased in patient urine pellets and showed a direct relationship with albuminuria. Collectively, these results suggest that the Rab-Rabphilin system could be involved in the alterations observed in injured podocytes and that a mechanism may be activated to reduce damage through the vesicular transport enhancement directed by this system.

scholarly journals Exposure of Toluene Diisocyanate Induces DUSP6 and p53 through Activation of TRPA1 Receptor

2022 ◽  
Vol 23 (1) ◽  
pp. 517
Author(s):  
Soee Kim ◽  
Min Kim ◽  
Jung-Suk Sung
Keyword(s):  
Manufacturing Industry ◽  
Mrna Level ◽  
Global Gene Expression ◽  
Receptor Activation ◽  
Toluene Diisocyanate ◽  
Protein Levels ◽  
Dual Specificity ◽  
Specific Antagonist ◽  
The Impact ◽  
Cancerous Cells

Toluene diisocyanate (TDI), a major intermediate agent used in the manufacturing industry, causes respiratory symptoms when exposed to the human body. In this study, we aimed to determine the molecular mechanism of TDI toxicity. To investigate the impact of TDI exposure on global gene expression, we performed transcriptomic analysis of human bronchial epithelial cells (BEAS-2B) after TDI treatment. Differentially expressed genes (DEGs) were sorted and used for clustering and network analysis. Among DEGs, dual-specificity phosphatase 6 (DUSP6) was one of the genes significantly changed by TDI exposure. To verify the expression level of DUSP6 and its effect on lung cells, the mRNA and protein levels of DUSP6 were analyzed. Our results showed that DUSP6 was dose-dependently upregulated by TDI treatment. Thereby, the phosphorylation of ERK1/2, one of the direct inhibitory targets of DUSP6, was decreased. TDI exposure also increased the mRNA level of p53 along with its protein and activity which trans-activates DUSP6. Since TRPA1 is known as a signal integrator activated by TDI, we analyzed the relevance of TRPA1 receptor in DUSP6 regulation. Our data revealed that up-regulation of DUSP6 mediated by TDI was blocked by a specific antagonist against TRPA1. TDI exposure attenuated the apoptotic response, which suggests that it promotes the survival of cancerous cells. In conclusion, our results suggest that TDI induces DUSP6 and p53, but attenuates ERK1/2 activity through TRPA1 receptor activation, leading to cytotoxicity.

scholarly journals Netrin-1 and kidney injury. I. Netrin-1 protects against ischemia-reperfusion injury of the kidney

2008 ◽  
Vol 294 (4) ◽  
pp. F739-F747 ◽  
Author(s):  
Weiwei Wang ◽  
W. Brian Reeves ◽  
Ganesan Ramesh
Keyword(s):  
Cell Activation ◽  
Ischemia Reperfusion Injury ◽  
Vascular Endothelial Cells ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Endothelial Cell Activation ◽  
Protein Levels ◽  
Peritubular Capillaries ◽  
The Impact

Endogenous mechanisms exist to limit inflammation. One such molecule is netrin. This study examined the impact of ischemia-reperfusion (I/R) on netrin expression and the role of netrin in preventing renal inflammation and injury. All three isoforms of netrin (1, 3, and 4) are expressed in normal kidney. I/R significantly downregulated netrin-1 and -4 mRNA expression, whereas expression of netrin-3 was moderately upregulated at 24 h of reperfusion. The netrin receptor UNC5B mRNA increased at 3 h and but decreased at later time points. Expression of a second netrin receptor, DCC, was not altered significantly. I/R was associated with dramatic changes in netrin-1 protein abundance and localization. Netrin-1 protein levels increased between 3 and 24 h after reperfusion. Immunolocalization showed an interstitial distribution of netrin-1 in sham-operated kidneys which colocalized with Von Willebrand Factor suggesting the presence of netrin-1 in peritubular capillaries. After I/R, interstitial netrin-1 expression decreased and netrin-1 appeared in tubular epithelial cells. By 72 h after reperfusion, netrin-1 reappeared in the interstitium while tubular epithelial staining decreased significantly. Downregulation of netrin-1 in the interstitium corresponded with increased MCP-1 and IL-6 expression and infiltration of leukocytes into the reperfused kidney. Administration of recombinant netrin-1 significantly improved kidney function (blood urea nitrogen: 161 ± 7 vs. 104 ± 24 mg/dl, creatinine: 1.3 ± 0.07 vs. 0.75 ± 0.16 mg/dl, P < 0.05 at 24 h) and reduced tubular damage and leukocyte infiltration in the outer medulla. These results suggest that downregulation of netrin-1 in vascular endothelial cells may promote endothelial cell activation and infiltration of leukocytes into the kidney thereby enhancing tubular injury.

Potential and limitations of bovine-specific arrays for the analysis of mRNA levels in early development: preliminary analysis using a bovine embryonic array

2005 ◽  
Vol 17 (2) ◽  
pp. 47 ◽  
Author(s):  
Marc-André Sirard ◽  
Isabelle Dufort ◽  
Maud Vallée ◽  
Lyne Massicotte ◽  
Catherine Gravel ◽  
...  
Keyword(s):  
Early Development ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Mrna Level ◽  
Cdna Array ◽  
Blastocyst Stage ◽  
Preimplantation Embryos ◽  
Mrna Levels ◽  
The Impact

New insights into the early development of large mammals are becoming available through the measurement of differential mRNA levels in oocytes and preimplantation embryos. These advances in knowledge are rapidly picking up in pace, mainly owing to the advantages brought by new molecular biology approaches being developed. The possibility of amplifying the starting material and therefore making measurements in single embryo units is now feasible. With these tools, the evaluation of variations in gene expression patterns during the preimplantation period or the impact of culture on mRNA levels is now possible. However, it is important to keep in mind that these methods still have limitations associated with sample preparation or the use of the appropriate controls. Even proper methods of analysis are very important to achieve the full benefit of the application of these tools. The present paper describes some of the potential, as well as limitations, of mRNA level analysis in early embryos, especially for microarray analysis. We have generated a bovine cDNA array (>2000 clones) that contains expressed sequence tags (ESTs) collected from various preimplantation development stages. Using this chip, we have initiated the characterisation of global mRNA level patterns of several key developmental stages from the immature oocyte to the blastocyst stage. As expected, the hybridisation results indicate very different expression profiles involving hundreds of genes when comparing oocyte and blastocyst samples to a reference mRNA sample made from a pool of ESTs from pooled somatic tissues. Although this array is still in its preliminary stage and the EST bank has not been processed to contain only unigenes, it is already a very useful tool for discovering candidate genes that may play important roles during early embryonic life.

scholarly journals Clinical relevance of TP53 hotspot mutations in high-grade serous ovarian cancers

2019 ◽  
Vol 122 (3) ◽  
pp. 405-412 ◽  
Author(s):  
Musaffe Tuna ◽  
Zhenlin Ju ◽  
Kosuke Yoshihara ◽  
Christopher I. Amos ◽  
Janos L. Tanyi ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Proportional Hazards ◽  
Expression Patterns ◽  
Cox Proportional Hazards ◽  
Response To Therapy ◽  
High Grade ◽  
Missense Mutations ◽  
Protein Levels ◽  
Hotspot Mutations ◽  
The Impact

Abstract Background Mutation of TP53 is the most frequent genetic alteration in high-grade serous ovarian cancer (HGSOC). The impact of hotspot mutations of TP53 and protein levels on patient outcomes in HGSOC has not been fully elucidated. Methods The study population (n = 791) comprised of HGSOC samples with TP53 mutation from TCGA and other publicly available data. Univariate and multivariate cox proportional hazards regression analyses were used to select variables that were correlated with patient survival. Results We assessed the effects of TP53 mutations based on type and individual hotspot mutations on patient outcomes in HGSOC. Only hotspot mutations were associated with outcomes. Three hotspot mutations: G266, Y163C, and R282, in aggregate were associated with a worsened overall and recurrence-free survival compared with other hotspot mutations (p < 0.0001 and p = 0.001), other non-hotspot missense mutations (p < 0.0001 and p = 0.008), truncated mutations (p < 0.0001 and p = 0.001), and all other mutations (p < 0.0001 and p = 0.001). Specific hotspot mutations were associated with different protein expression patterns consistent with different functions. Conclusions This study provides evidence that individual TP53 hotspot mutations have different impact on HGSOC patient outcomes and potentially TP53 function. Thus the status of particular TP53 aberrations could influence response to therapy and selection of therapeutic agents.

1.25 Dihydroxyvitamin D3 Attenuates Hypertrophy Markers in Cardiomyoblast H9c2 Cells: Evaluation of Sirtuin3 mRNA and Protein Level

2019 ◽  
Vol 89 (3-4) ◽  
pp. 144-151
Author(s):  
Fatemeh Jahanifar ◽  
Akram Astani ◽  
Shahnaz Shekarforoosh ◽  
Mohabbat Jamhiri ◽  
Fereshteh Safari ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Natriuretic Peptide ◽  
Molecular Mechanisms ◽  
Mrna Level ◽  
Negative Regulator ◽  
Blue Staining ◽  
H9c2 Cells ◽  
Intact Cells ◽  
Dihydroxyvitamin D3 ◽  
Protein Levels

Abstract. Background: The cellular and molecular mechanisms of cardioprotective effects of Vitamin D are poorly understood. Given the essential role of sirtuin-3 (SIRT3) as an endogenous negative regulator of cardiac hypertrophy, this study was designed to investigate the effect of 1, 25-dihydroxyvitamin D3 (calcitriol) on hypertrophy markers and SIRT3 mRNA and protein levels following angiotensin II induced - hypertrophy in cardiomyoblast H9c2 cells. Methods: Rat cardiomyoblast H9c2 cells were treated for 48 hr with angiotensin II alone (Ang group) or in combination with 1, 10 and 100 nM of calcitriol (C + Ang groups). Intact cells served as control (Ctl). The cell area was measured using methylene blue staining. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and SIRT3 transcription levels were measured by real time RT-PCR. SIRT3 protein expression was evaluated using western blot technique. Results: The results showed that in Ang group cell size was increase by 128.4 ± 15% (P < 0.001 vs. Ctl) whereas in C100 + Ang group it was increased by 21.3 ± 6% (P < 0.001 vs. Ang group). Calcitriol pretreatment decreased ANP mRNA level significantly (P < 0.05) in comparison with Ang group (Ang: 75.5 ± 15%, C100 + Ang: 19.2 ± 9%). There were no significant differences between Ang group and cells pretreated with 1 and 10 nM of calcitriol. SIRT3 at mRNA and protein levels did not change significantly among the experimental groups. Conclusions: In conclusion, pretreatment with calcitriol (100 nM) prevents Ang II-induced hypertrophy in cardiomyoblast H9c2 cells. This probably occurs through other pathways except SIRT3 upregulation.

The Impact of Angiotensin-II Receptor Blockers on Cardiovascular Events in Hypertensive Patients – Evidence from Real-life Databases

2010 ◽  
Vol 6 (3) ◽  
pp. 33
Author(s):  
Robert J Petrella ◽  
Keyword(s):  
Angiotensin Ii ◽  
Antihypertensive Drugs ◽  
Real Life ◽  
Angiotensin Ii Receptor Blockers ◽  
Angiotensin Ii Receptor ◽  
Real World Setting ◽  
Actual Experience ◽  
Receptor Blockers ◽  
Randomised Controlled ◽  
The Impact

It is widely recognised that hypertension is a major risk factor for the development of future cardiovascular (CV) events, which in turn are a major cause of morbidity and mortality. Blood pressure (BP) control with antihypertensive drugs has been shown to reduce the risk of CV events. Angiotensin-II receptor blockers (ARBs) are one such class of antihypertensive drugs and randomised controlled trials (RCTs) have shown ARB-based therapies to have effective BP-lowering properties. However, data obtained under these tightly controlled settings do not necessarily reflect actual experience in clinical practice. Real-life databases may offer alternative information that reflects an uncontrolled real-world setting and complements and expands on the findings of clinical trials. Recent analyses of practice-based real-life databases have shown ARB-based therapies to be associated with better persistence and adherence rates and with superior BP control than non-ARB-based therapies. Analyses of real-life databases also suggest that ARB-based therapies may be associated with a lower risk of CV events than other antihypertensive-drug-based therapies.

Pengaruh Lama Pengasinan Terhadap Kadar Protein Putih Telur Itik

2014 ◽  
Vol 1 (1) ◽  
pp. 36 ◽  
Author(s):  
Siti Fatimah ◽  
Muji Rahayu ◽  
Siti Aminah
Keyword(s):  
Protein Level ◽  
Egg White ◽  
Special Treatment ◽  
Egg White Protein ◽  
Protein Levels ◽  
Duck Egg ◽  
Egg Period ◽  
Graph Presentation ◽  
And Control ◽  
The Impact

Background : Egg  is one of the animal protein source, which has delicious taste, easy to digest and highly nutritious. Besides its affordable price, its supply availability is unquestionable as well. However, due to its short storability, it requires special treatment, such as preserving, to store it for long period. One way to preserve the egg is by pickling egg, which generally requires seven to ten days of marinating. During the process of marinating, there will be a visual change of egg white and yolk. Their structures  will be more solid (the occurrence of thickening process) because salinization will lead to protein denaturalization. Consequently, it has an influence as well towards the content of egg white protein of duck egg. This study is aimed to explore the impact of various time of pickling egg towards egg white protein of duck egg. Method  : The study where takes place in a laboratories, is a true experimental study for the reason that the researcher must provide intervention, hence all of potentially confounding variables are manageable. Samples that had been used in this study are duck eggs which were bought from North Brebes. This study is expected to generate data from four various time of pickling egg and control (no treatment). Since there are four samples, accordingly the number of data resulted are twenty. The resulted data will be descriptively presented in table, graph, presentation, and narration. Result  : Protein level examination within duck white egg shows changes  in protein levels that occurs in every variation of pickling egg time, where the average results of the assay of duck egg white protein is 14.94% without treatment (control), in five days of pickling time is 13.68%, in seven days of pickling time is 13.29%, in nine days of pickling time is 12.87% and eleven days of pickling time is 12.78%. Conclusion  : There is a significant impact among the period of pickling time to the protein level degradation of duck white egg. Keywords : Duck egg, period of pickling time, level protein of duck white egg.

Effects of Food Protein Levels on Haematological Parameters of Growing Japanese Quails (Coturnix Coturnix Japonica Temminck & Schlegel, 1849)

2020 ◽  
Vol 6 (6) ◽  
pp. 94-100
Author(s):  
Serge-Olivier Konan KOUASSI ◽  
◽  
Yves Bénarèce Tra DJE BI ◽  
Soualio KAMAGATE ◽  
Mathieu Nahounou BLEYERE ◽  
...  
Keyword(s):  
Crude Protein ◽  
Hematological Parameters ◽  
Coturnix Japonica ◽  
Food Protein ◽  
Coturnix Coturnix Japonica ◽  
Coturnix Coturnix ◽  
Protein Levels ◽  
Dietary Crude Protein ◽  
Japanese Quails ◽  
The Impact

The study aims to determine the impact of dietary crude protein levels on the hematological parameters of Japanese quail from growth to ovipositor. To this end, five feeds with different crude protein levels (18, 20, 22, 24 and 26%) were supplied to 700 quails of three weeks of age. These were subdivided into six batches, including three batches of females and three batches of males for each feed group. After subjecting the quails to diets containing the different protein levels, four samples were taken at the fourth, fifth, sixth and seventh week of age. The samples taken were analyzed using an SYSMEX XN 350 automated hematological analyzer. The results of this investigation indicated that non-significant differences (P > 0.05) were observed in hematological parameters in both female and male quails. This study showed that dietary crude protein levels had no impact on the health status of Japanese quails. Keywords: Japanese quails, Crude protein, Hematological parameters.

The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Control ◽  
In Vitro Proliferation ◽  
Cell Functions ◽  
Mirna Expression Profiles ◽  
Multiple Processes ◽  
The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic &#946;-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in &#946;-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of &#946;-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into &#946;-cells, resulting in enhanced &#946;-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of &#946;-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived &#946;-cells to therapeutically relevant outputs will be discussed as well.

Fluoxetine Protects against Dendritic Spine Loss in Middle-aged APPswe/PSEN1dE9 Double Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Early Stage ◽  
Learning Ability ◽  
Middle Aged ◽  
Protein Levels ◽  
Spine Pathology ◽  
The Impact

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

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