scholarly journals Dehydroepiandrosterone-Regulated Testosterone Biosynthesis via Activation of the ERK1/2 Signaling Pathway in Primary Rat Leydig Cells

2015 ◽  
Vol 36 (5) ◽  
pp. 1778-1792 ◽  
Author(s):  
Lin Liu ◽  
Jian Kang ◽  
Xiao Ding ◽  
Di Chen ◽  
Yingqiao Zhou ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Leydig Cells ◽  
Expression Level ◽  
Target Cells ◽  
Protein Expression Level ◽  
Expression Levels ◽  
Creb Protein ◽  
Protein Levels ◽  
Testosterone Biosynthesis

Background: Dehydroepiandrosterone decreases with age and this reduction has been shown to be associated with physical health in human. Some studies have suggested that the effects of DHEA are exerted after it is biotransformed into more biologically-active hormones in peripheral target cells. This study investigated the effects of DHEA on the testosterone biosynthesis and possible signaling pathway mechanism underlying these DHEA effects were also explored in primary rat Leydig cells. Methods: Primary Leydig cells were treated with DHEA and then detected testosterone content by RIA and steroidogenic enzymes, ERK1/2 signal pathway factors protein expression level by Western blot. Results: Incubation of primary Leydig cells with DHEA significantly increased testosterone content and 3β-HSD and 17β-HSD protein expression levels, while aromatase protein expression levels were decreased. Compared with the control group, p-ERK1/2 and p-CREB protein levels were significantly increased in DHEA-treated groups. Testosterone content was significantly decreased in the DHEA-treated group pre-incubated with U0126 (p-ERK1/2 inhibitor). Additionally, the rise in p-ERK1/2, 3β-HSD and 17β-HSD protein levels induced by DHEA was reversed when cells were pre-incubated with U0126. Interestingly, no significant difference was found in aromatase protein expression level in cells pretreated with U0126. Conclusion: These findings demonstrate that (a) exogenous DHEA might preferentially convert to testosterone rather than estradiol due to the up-regulation of 3β-HSD and 17β-HSD protein levels and the down-regulation of aromatase protein level in primary Leydig cells, and (b) the action of DHEA is at least partly associated with the elevation of p-ERK1/2 and p-CREB protein levels.

Impact of Pirin Protein Expression Level on NF-κB Signaling Pathway Activation

2010 ◽  
Author(s):  
Kamil Brzóska ◽  
Marcin Kruszewski ◽  
Carlos Granja ◽  
Claude Leroy
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Expression Level ◽  
Protein Expression Level ◽  
Pathway Activation

scholarly journals Non-monotonic cellular responses to heterogeneity in talin protein expression-level

2015 ◽  
Vol 7 (10) ◽  
pp. 1171-1185 ◽  
Author(s):  
Alexa Kiss ◽  
Xiaowei Gong ◽  
Jacob M. Kowalewski ◽  
Hamdah Shafqat-Abbasi ◽  
Staffan Strömblad ◽  
...  
Keyword(s):  
Protein Expression ◽  
Single Cells ◽  
Cellular Responses ◽  
Expression Level ◽  
Live Migration ◽  
Protein Expression Level ◽  
Expression Levels ◽  
Correlative Imaging

Correlative imaging in single-cells of both live migration and post-fixation talin-labeling revealed non-monotonic correspondences between cellular properties and talin expression-levels.

A novel silent mutation E83E of αA-crystallin in age-related cataract with impaired chaperone function

2020 ◽  
Author(s):  
Fanqian Song ◽  
Dongrui Liu ◽  
Liyao Sun ◽  
Chao Wang ◽  
Xi Wei ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Protein Expression ◽  
Cell Morphology ◽  
Expression Level ◽  
Silent Mutation ◽  
Protein Expression Level ◽  
Uv Treatment ◽  
Expression Levels ◽  
Chaperone Function ◽  
Age Related

Abstract Background Age-related cataract (ARC) is the leading cause of blindness of the aged, influenced by environmental factors and genetic factors. However, it is scanty in gene mutation studies. The study aims to expand knowledge of etiology of ARC. Methods Peripheral blood samples of ARC patients were collected to screen αA-crystallin (CRYAA) gene mutations by single strand conformation polymorphism assay. Cell morphology, protein expression level and chaperone function of CRYAA in HLE B-3 cell line influenced by mutant CRYAA were next analyzed. Chaperone function of mutant CRYAA was measured by aggregation assay in physiological status, heat treatment (42℃) and ultraviolet (UV) treatment. Cell morphology and protein expression level effected by UV in human lens epithelial B3 (HLE B-3) cells and human anterior lens capsules (ALCs) were further analyzed. Results We identified a novel silent mutation in CRYAA (c.249G > A, p.E83E) among 300 ARC patients. CRYAA-E83E may up-regulate the CRYAA expression levels of both mRNA and protein, and change the distribution of CRYAA in HLE B-3 cells. Compared to wild type CRYAA (CRYAA-WT), CRYAA-E83E showed lower chaperone function after 42℃ heat treatment and UV treatment. Meanwhile, after UV treatment, HLE B-3 cells and lens epithelial cells in human ALCs showed irregular and flatten morphology; decreased CRYAA expression levels; increased laminin γ2 expression levels, and changed epithelial-mesenchymal transition (EMT) related protein expression levels. Conclusions The E83E mutation of CRYAA is a potential pathogenic mutation, considering its influence on the expression level, intracellular distribution and chaperone function of CRYAA.

scholarly journals Comprehensive Analysis of ESRRA in Endometrial Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382199208
Author(s):  
Shufang Wang ◽  
Xinlong Huo
Keyword(s):  
Endometrial Cancer ◽  
Protein Expression ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Operating Characteristics ◽  
Protein Expression Level ◽  
Normal Tissues

Background: Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet. Methods: Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability. Results: A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4+ naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC. Conclusions: Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.

scholarly journals Use of molecular biomarkers to estimate manganese requirements for broiler chickens from 22 to 42 d of age

2016 ◽  
Vol 116 (9) ◽  
pp. 1512-1518 ◽  
Author(s):  
Lin Lu ◽  
Bin Chang ◽  
Xiudong Liao ◽  
Runlian Wang ◽  
Liyang Zhang ◽  
...  
Keyword(s):  
Dna Binding ◽  
Protein Expression ◽  
Broiler Chickens ◽  
Mrna Level ◽  
Molecular Biomarkers ◽  
Expression Level ◽  
Response Curves ◽  
Expression Levels ◽  
Soyabean Meal ◽  
Mnsod Activity

AbstractThe present study was carried out to evaluate dietary Mn requirements of broilers from 22 to 42 d of age using molecular biomarkers. Chickens were fed a conventional basal maize–soyabean meal diet supplemented with Mn as Mn sulphate in graded concentrations of 20 mg Mn/kg from 0 to 140 mg Mn/kg of diet for 21 d (from 22 to 42 d of age). The Mn response curves were fitted for ten parameters including heart Mn-containing superoxide dismutase (MnSOD) mRNA and its protein expression levels and the DNA-binding activities of specificity protein 1 (Sp1) and activating protein-2 (AP-2). Heart MnSOD mRNA and protein expression levels showed significant quadratic responses (P<0·01), and heart MnSOD activity showed a broken-line response (P<0·01), whereas Mn content and DNA-binding activities of Sp1 and AP-2 in the heart displayed linear responses (P<0·01) to dietary Mn concentrations, respectively. The estimates of dietary Mn requirements were 101, 104 and 94 mg/kg for full expressions of MnSOD mRNA level, MnSOD protein level and MnSOD activity in the heart, respectively. Our findings indicate that heart MnSOD mRNA expression level is a more reliable indicator than heart MnSOD protein expression level and its activity for the evaluation of Mn requirement of broilers, and about 100 mg Mn/kg of diet is required for the full expression of heart MnSOD in broilers fed the conventional basal maize–soyabean meal diet from 22 to 42 d of age.

scholarly journals Evaluation of Patched-1 Protein Expression Level in Low Risk and High Risk Basal Cell Carcinoma Subtypes

2019 ◽  
Vol 20 (9) ◽  
pp. 2851-2857 ◽  
Author(s):  
Rowida Almomani ◽  
Mariam Khanfar ◽  
Khaldon Bodoor ◽  
Firas Al-Qarqaz ◽  
Mohammad Alqudah ◽  
...  
Keyword(s):  
High Risk ◽  
Basal Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Low Risk ◽  
Expression Level ◽  
Protein Expression Level ◽  
Patched 1

scholarly journals Determination of CYP450 Expression Levels in the Human Small Intestine by Mass Spectrometry-Based Targeted Proteomics

2021 ◽  
Vol 22 (23) ◽  
pp. 12791
Author(s):  
Alexia Grangeon ◽  
Valérie Clermont ◽  
Azemi Barama ◽  
Fleur Gaudette ◽  
Jacques Turgeon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Small Intestine ◽  
Protein Expression ◽  
Mrna Levels ◽  
Targeted Proteomics ◽  
Tissue Samples ◽  
Human Organ ◽  
Expression Levels ◽  
Protein Levels ◽  
Human Small Intestine

The human small intestine can be involved in the first-pass metabolism of drugs. Under this condition, members of the CYP450 superfamily are expected to contribute to drug presystemic biotransformation. The aim of this study was to quantify protein expression levels of 16 major CYP450 isoforms in tissue obtained from nine human organ donors in seven subsections of the small intestine, i.e., duodenum (one section, N = 7 tissue samples), jejunum (three subsections (proximal, mid and distal), N = 9 tissue samples) and ileum (three subsections, (proximal, mid and distal), N = 9 tissue samples), using liquid chromatography tandem mass spectrometry (LC-MS/MS) based targeted proteomics. CYP450 absolute protein expression levels were compared to mRNA levels and enzyme activities by using established probe drugs. Proteins corresponding to seven of sixteen potential CYP450 isoforms were detected and quantified in various sections of the small intestine: CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, CYP3A5 and CYP4F2. Wide inter-subject variability was observed, especially for CYP2D6. CYP2C9 (p = 0.004) and CYP2C19 (p = 0.005) expression levels decreased along the small intestine. From the duodenum to the ileum, CYP2J2 (p = 0.001) increased, and a trend was observed for CYP3A5 (p = 0.13). CYP3A4 expression was higher in the jejunum than in the ileum (p = 0.03), while CYP4F2 expression was lower in the duodenum compared to the jejunum and the ileum (p = 0.005). CYP450 protein levels were better correlated with specific isoform activities than with mRNA levels. This study provides new data on absolute CYP450 quantification in human small intestine that could improve physiologically based pharmacokinetic models. These data could better inform drug absorption profiles while considering the regional expression of CYP450 isoforms.

Xihuang Pill inhibits the development of DMBA combined estrogen and progesterone induced breast precancerous lesions rats by PI3K/AKT/mTOR signaling pathway

2021 ◽  
Author(s):  
Huanfang Fan ◽  
Dehui Li ◽  
Na Guo ◽  
Chunxia Sun ◽  
Jingfei Dong ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Breast Tissue ◽  
Precancerous Lesions ◽  
Precancerous Lesion ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Vegf Mrna ◽  
Expression Levels ◽  
Pten Mrna

Abstract Objective. To study the inhibitory effect of Xihuang Pill on the development of DMBA combined estrogen and progesterone induced breast precancerous lesions rats by PI3K/AKT/mTOR signaling pathway, and to explore the effect of Xihuang Pill in preventing and treating breast cancer. Method. Establishment of a rat model of breast precancerous lesion with DMBA combined estrogen and progesterone sequential induction for 10 weeks. Xihuang Pill was administered by gavage continuously for 4 weeks. Take rat breast tissue and stain with hematoxylin- eosin (HE). The pathomorphological changes were observed with light microscope; TUNEL staining to detect cell apoptosis in breast tissue; Western blot was used to detect the protein expression of P-PI3K, P-AKT (S473), P-AKT (T308), PTEN, P-Tuberin/TSC2, P-Tuberin (p-S939), p-mTOR, P-4E-BP1 in breast tissues. The qRT-PCR was used to detect the gene expression of PTEN mRNA and VEGF mRNA. Immunohistochemistry was used to detect the protein expression of P-S6, p-p70s6k and VEGF. Result. Compared with the disease model group, the low, middle and high dose Xihuang Pill groups could significantly reduce the degree of breast pathology, and the number of apoptosis of breast precancerous lesions cells increased with the increase of Xihuang Pill dose; The expression levels of P-PI3K, P-AKT (S473), P-AKT (T308), p-mTOR, P-4E-BP1, p-S6, p-p70S6K, VEGF protein and VEGF mRNA dropped with the increase of Xihuang Pill dose. The expression levels of PTEN, P-Tuberin/TSC2, P-Tuberin (p-S939) protein and PTEN mRNA elevated with the increase of Xihuang Pill dose. Conclusion. Xihuang Pill can promote the apoptosis of breast precancerous lesion cells and reduce the proliferation of vascular endothelial cells, and then inhibit the progression of breast precancerous lesions. Its mechanism probably associated with the regulation of PI3K/AKT/mTOR pathway related gene protein expression.

scholarly journals Piceatannol Ameliorates Hepatic Oxidative Damage and Mitochondrial Dysfunction of Weaned Piglets Challenged with Diquat

Animals ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1239
Author(s):  
Peilu Jia ◽  
Shuli Ji ◽  
Hao Zhang ◽  
Yanan Chen ◽  
Tian Wang
Keyword(s):  
Oxidative Damage ◽  
Protein Expression ◽  
Complex I ◽  
Sirtuin 1 ◽  
Expression Level ◽  
Control Group ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Protein Expression Level ◽  
Atp Production

The liver is an organ that produces large amounts of reactive oxygen species (ROS). Human infants or piglets are prone to oxidative damage due to their uncompleted development of the antioxidant system, causing liver disease. Piceatannol (PIC) has been found to have significant antioxidant effects. The aim of this experiment was to investigate the effects of PIC on the liver in piglets experiencing oxidative stress caused by diquat (DQ). After weaning, 54 male piglets (Duroc × [Landrace × Yorkshire]) were selected and randomly divided into three treatment groups: the CON group, the DQ-CON group, and the DQ-PIC group. The two challenged groups were injected with DQ and then orally administrated either PIC or another vehicle solution, while the control group was given sterile saline injections and an orally administrated vehicle solution. Compared to the results of the CON group, DQ increased the percentage of apoptosis cells in the liver, also decreased the amount of reduced glutathione (GSH) and increased the concentration of malondialdehyde (MDA). In addition, the adenosine triphosphate (ATP) production, activities of mitochondrial complex I, II, III, and V, and the protein expression level of sirtuin 1 (SIRT1) were inhibited by DQ. Furthermore, PIC supplementation inhibited the apoptosis of hepatic cells caused by DQ. PIC also decreased MDA levels and increased the amount of GSH. Piglets given PIC supplementation exhibited increased activities of mitochondrial complex I, II, III, and V, the protein expression level of SIRT1, and the ATP production in the liver. In conclusion, PIC affected the liver of piglets by improving redox status, preserving mitochondrial function, and preventing excessive apoptosis.

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