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 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 Intrauterine growth restriction affects hippocampal dual specificity phosphatase 5 gene expression and epigenetic characteristics

2011 ◽  
Vol 43 (20) ◽  
pp. 1160-1169 ◽  
Author(s):  
Xingrao Ke ◽  
Robert A. McKnight ◽  
Diana Caprau ◽  
Shannon O'Grady ◽  
Qi Fu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cpg Methylation ◽  
Histone Code ◽  
Male Rat ◽  
Female Rat ◽  
Dual Specificity Phosphatase ◽  
Intrauterine Growth ◽  
Protein Levels ◽  
Dual Specificity ◽  
The Impact

Intrauterine growth retardation (IUGR) predisposes humans toward hippocampal morbidities, such as impaired learning and memory. Hippocampal dual specificity phosphatase 5 (DUSP5) may be involved in these morbidities because DUSP5 regulates extracellular signal-regulated kinase phosphorylation (Erk). In the rat, IUGR causes postnatal changes in hippocampal gene expression and epigenetic characteristics. However, the impact of IUGR upon hippocampal DUSP5 expression and epigenetic characteristics is not known. We therefore hypothesized that IUGR affects hippocampal 1) DUSP5 expression, DNA CpG methylation, and histone code, and 2) erk1/2 phosphorylation in a well-characterized rat model of IUGR. We found that IUGR significantly decreased DUSP5 expression in the day of life (DOL) 0 and 21 male rat, while decreasing only DUSP5 protein levels in the DOL21 female rat. Fluorescent in situ hybridization and immunohistochemistry analyses localized the changes in DUSP5 mRNA and protein, many of which occurred in the dentate gyrus. IUGR also caused sex-specific differences in DNA CpG methylation and histone code in two sites of the hippocampal DUSP5 gene, a 5′-flanking specificity protein-1 (SP1) site and exon 2. Finally, when IUGR decreased DUSP5 protein levels, Erk phosphorylation increased. We conclude that IUGR affects hippocampal DUSP5 expression and epigenetic characteristics in a sex-specific manner.

scholarly journals In Vitro Effects of Arthrocen, an Avocado/Soy Unsaponifiables Agent, on Inflammation and Global Gene Expression in Human Monocytes

2017 ◽  
Vol 9 (4) ◽  
pp. 31 ◽  
Author(s):  
Jared F Taylor ◽  
Ramin Goudarzi ◽  
Puya G Yazdi ◽  
Brian Allen Pedersen
Keyword(s):  
Synergistic Effect ◽  
Mrna Level ◽  
Global Gene Expression ◽  
Transcript Level ◽  
Symptomatic Treatment ◽  
Transcriptional Level ◽  
Vitro Assay ◽  
Protein Levels ◽  
Model Cell

Osteoarthritis (OA) is the most common form of arthritis. Symptomatically characterized by stiffness and pain, OA is a chronic degenerative disease of joints. Of note, there is growing interest in the potential use of plant-based compounds for symptomatic treatment of OA. Arthrocen is a plant-derived agent consisting of a one to two ratio of avocado and soy unsaponifiable extracts. In order to decipher the potential mechanisms of Arthrocen's action at the molecular level, we employed an in vitro assay using cultured human THP-1 cells (a model cell line for monocytes) to study its effects. By pairing protein arrays enriched for inflammatory markers, transcriptomic pathway analysis using RNA-Sequencing, and eicosanoid specific lipidomics, we have begun to unravel its potential mechanism of action. Specifically, we found that Arthrocen can attenuate the inflammatory response at the transcript level while inducing significant changes in numerous cytokines. Furthermore, we discovered that while Arthrocen alone did not increase IL-8 or MCP-1 levels, its presence had a synergistic effect on the observed increase in response to LPS stimulation. Additionally, this synergistic effect of Arthrocen on LPS stimulation of IL-8 and MCP-1 protein levels was also observed at the mRNA level and suggests a regulatory mechanism at the transcriptional level. Interestingly, Arthrocen induced no changes in any of the eicosanoids studied. This multi-omics approach implies that Arthrocen functions at the level of gene transcription to dampen inflammation mediated by monocytes in OA.

A Study on the Impact of Family-friendly Certification on Financial Performance of SMEs: Focusing on the Manufacturing Industry

2019 ◽  
Vol 118 (2) ◽  
pp. 7-12
Author(s):  
Ok-Hee Park ◽  
Kwan-sik Na ◽  
Seok-Kee Lee
Keyword(s):  
Financial Performance ◽  
Family Life ◽  
Manufacturing Industry ◽  
Work And Family ◽  
Family Friendly ◽  
The Future ◽  
The Impact

Background/Objectives: The purpose of the paper is to examine how family-friendly certificates introduced to pursue the compatibility of work and family life affect the financial performance of small and medium-sized manufacturers, and to provide useful information to companies considering the introduction of this system in the future.

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.

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.

scholarly journals Association of temporary Environmental Protection Agency regulation suspension with industrial economic viability and local air quality in California, United States

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Emily Chang ◽  
Kenneth Zhang ◽  
Margaret Paczkowski ◽  
Sara Kohler ◽  
Marco Ribeiro
Keyword(s):  
United States ◽  
Air Quality ◽  
Environmental Protection ◽  
Environmental Protection Agency ◽  
Manufacturing Industry ◽  
Economic Viability ◽  
Treatment Control ◽  
Oil Refineries ◽  
Pollution Levels ◽  
The Impact

Abstract Background This study seeks to answer two questions about the impacts of the 2020 Environmental Protection Agency’s enforcement regulation rollbacks: is this suspension bolstering the economic viability of industries as oil and manufacturing executives claim they will and are these regulations upholding the agency’s mission of protecting the environment? Results To answer the former question, we utilized 6 months of state employment level data from California, United States, as a method of gauging the economic health of agency-regulated industries. We implemented a machine learning model to predict weekly employment data and a t-test to indicate any significant changes in employment. We found that, following California's state-issued stay-at-home order and the agency’s regulation suspension, oil and certain manufacturing industries had statistically significant lower employment values. To answer the latter question, we used 10 years of PM2.5 levels in California, United States, as a metric for local air quality and treatment–control county pairs to isolate the impact of regulation rollbacks from the impacts of the state lockdown. Using the agency’s data, we performed a t-test to determine whether treatment–control county pairs experienced a significant change in PM2.5 levels. Even with the statewide lockdown—a measure we hypothesized would correlate with decreased mobility and pollution levels—in place, counties with oil refineries experienced the same air pollution levels when compared to historical data averaged from the years 2009 to 2019. Conclusions In contrast to the expectation that the suspension would improve the financial health of the oil and manufacturing industry, we can conclude that these industries are not witnessing economic growth with the suspension and state shutdown in place. Additionally, counties with oil refineries could be taking advantage of these rollbacks to continue emitting the same amount of PM2.5, in spite of state lockdowns. For these reasons, we ask international policymakers to reconsider the suspension of enforcement regulations as these actions do not fulfill their initial expectations. We recommend the creation and maintenance of pollution control and prevention programs that develop emission baselines, mandate the construction of pollution databases, and update records of pollution emissions.

scholarly journals Dopamine Transporter Genetic Reduction Induces Morpho-Functional Changes in the Enteric Nervous System

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 465
Author(s):  
Silvia Cerantola ◽  
Valentina Caputi ◽  
Gabriella Contarini ◽  
Maddalena Mereu ◽  
Antonella Bertazzo ◽  
...  
Keyword(s):  
Nervous System ◽  
Small Intestine ◽  
Enteric Nervous System ◽  
Dopamine Transporter ◽  
Myenteric Plexus ◽  
Receptor Activation ◽  
D1 Receptor ◽  
Functional Changes ◽  
Neurochemical Coding ◽  
The Impact

Antidopaminergic gastrointestinal prokinetics are indeed commonly used to treat gastrointestinal motility disorders, although the precise role of dopaminergic transmission in the gut is still unclear. Since dopamine transporter (DAT) is involved in several brain disorders by modulating extracellular dopamine in the central nervous system, this study evaluated the impact of DAT genetic reduction on the morpho-functional integrity of mouse small intestine enteric nervous system (ENS). In DAT heterozygous (DAT+/−) and wild-type (DAT+/+) mice (14 ± 2 weeks) alterations in small intestinal contractility were evaluated by isometrical assessment of neuromuscular responses to receptor and non-receptor-mediated stimuli. Changes in ENS integrity were studied by real-time PCR and confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations (). DAT genetic reduction resulted in a significant increase in dopamine-mediated effects, primarily via D1 receptor activation, as well as in reduced cholinergic response, sustained by tachykininergic and glutamatergic neurotransmission via NMDA receptors. These functional anomalies were associated to architectural changes in the neurochemical coding and S100β immunoreactivity in small intestine myenteric plexus. Our study provides evidence that genetic-driven DAT defective activity determines anomalies in ENS architecture and neurochemical coding together with ileal dysmotility, highlighting the involvement of dopaminergic system in gut disorders, often associated to neurological conditions.

scholarly journals Differential Effects of Toll-Like Receptor Activation and Differential Mediation by MAP Kinases of Immune Responses in Microglial Cells

2021 ◽  
Author(s):  
Jaedeok Kwon ◽  
Christos Arsenis ◽  
Maria Suessmilch ◽  
Alison McColl ◽  
Jonathan Cavanagh ◽  
...  
Keyword(s):  
Map Kinase ◽  
Microglial Activation ◽  
Map Kinases ◽  
Mrna Level ◽  
Cell Types ◽  
Receptor Activation ◽  
Microglial Cells ◽  
Toll Like Receptor ◽  
Disease States ◽  
Nitrite Production

AbstractMicroglial activation is believed to play a role in many psychiatric and neurodegenerative diseases. Based largely on evidence from other cell types, it is widely thought that MAP kinase (ERK, JNK and p38) signalling pathways contribute strongly to microglial activation following immune stimuli acting on toll-like receptor (TLR) 3 or TLR4. We report here that exposure of SimA9 mouse microglial cell line to immune mimetics stimulating TLR4 (lipopolysaccharide—LPS) or TLR7/8 (resiquimod/R848), results in marked MAP kinase activation, followed by induction of nitric oxide synthase, and various cytokines/chemokines. However, in contrast to TLR4 or TLR7/8 stimulation, very few effects of TLR3 stimulation by poly-inosine/cytidine (polyI:C) were detected. Induction of chemokines/cytokines at the mRNA level by LPS and resiquimod were, in general, only marginally affected by MAP kinase inhibition, and expression of TNF, Ccl2 and Ccl5 mRNAs, along with nitrite production, were enhanced by p38 inhibition in a stimulus-specific manner. Selective JNK inhibition enhanced Ccl2 and Ccl5 release. Many distinct responses to stimulation of TLR4 and TLR7 were observed, with JNK mediating TNF protein induction by the latter but not the former, and suppressing Ccl5 release by the former but not the latter. These data reveal complex modulation by MAP kinases of microglial responses to immune challenge, including a dampening of some responses. They demonstrate that abnormal levels of JNK or p38 signalling in microglial cells will perturb their profile of cytokine and chemokine release, potentially contributing to abnormal inflammatory patterns in CNS disease states.

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