Regulation Of Receptor Binding Research Articles

Discovery of genes and proteins possibly regulating mean wool fibre diameter using cDNA microarray and proteomic approaches

Wool fibre diameter (WFD) is one of the wool traits with higher economic impact. However, the main genes specifically regulating WFD remain unidentified. In this current work we have used Agilent Sheep Gene Expression Microarray and proteomic technology to investigate the gene expression patterns of body side skin, bearing more wool, in Aohan fine wool sheep, a Chinese indigenous breed, and compared them with that of small tail Han sheep, a sheep bread with coarse wool. Microarray analyses showed that most of the genes likely determining wool diameter could be classified into a few categories, including immune response, regulation of receptor binding and growth factor activity. Certain gene families might play a role in hair growth regulation. These include growth factors, immune cytokines, solute carrier families, cellular respiration and glucose transport amongst others. Proteomic analyses also identified scores of differentially expressed proteins.

Potential Targets for Treatment of Coronavirus Disease 2019 (COVID-19): A Review of Qing-Fei-Pai-Du-Tang and Its Major Herbs.

COVID-19 has been declared a pandemic by WHO on March 11, 2020. No specific treatment and vaccine with documented safety and efficacy for the disease have been established. Hence it is of utmost importance to identify more therapeutics such as Chinese medicine formulae to meet the urgent need. Qing Fei Pai Du Tang (QFPDT), a Chinese medicine formula consisting of 21 herbs from five classical formulae has been reported to be efficacious on COVID-19 in 10 provinces in mainland China. QFPDT could prevent the progression from mild cases and shorten the average duration of symptoms and hospital stay. It has been recommended in the 6th and 7th versions of Clinical Practice Guideline on COVID-19 in China. The basic scientific studies, supported by network pharmacology, on the possible therapeutic targets of QFPDT and its constituent herbs including Ephedra sinica, Bupleurum chinense, Pogostemon cablin, Cinnamomum cassia, Scutellaria baicalensis were reviewed. The anti-oxidation, immuno-modulation and antiviral mechanisms through different pathways were collated. Two clusters of actions identified were cytokine storm prevention and angiotensin converting enzyme 2 (ACE2) receptor binding regulation. The multi-target mechanisms of QFPDT for treating viral infection in general and COVID-19 in particular were validated. While large scale clinical studies on QFPDT are being conducted in China, one should use real world data for exploration of integrative treatment with inclusion of pharmacokinetic, pharmacodynamic and herb-drug interaction studies.

Identification of skin-expressed genes possibly associated with wool growth regulation of Aohan fine wool sheep.

BackgroundSheep are valuable resources for the animal fibre industry. Therefore, identifying genes which regulate wool growth would offer strategies for improving the quality of fine wool. In this study, we employed Agilent sheep gene expression microarray and proteomic technology to compare the gene expression patterns of the body side (hair-rich) and groin (hairless) skins of Aohan fine wool sheep (a Chinese indigenous breed).ResultsComparing the body side to the groin skins (S/G) of Aohan fine wool sheep, the microarray study revealed that 1494 probes were differentially expressed, including 602 more highly expressed and 892 less highly expressed probes. The microarray results were verified by means of quantitative PCR. Cluster analysis could distinguish the body side skin and the groin skin. Based on the Database for Annotation, Visualization and Integrated Discovery (DAVID), 38 of the differentially expressed genes were classified into four categories, namely regulation of receptor binding, multicellular organismal process, protein binding and macromolecular complex. Proteomic study revealed that 187 protein spots showed significant (p < 0.05) differences in their respective expression levels. Among them, 46 protein entries were further identified by MALDI-TOF/MS analyses.ConclusionsMicroarray analysis revealed thousands of differentially expressed genes, many of which were possibly associated with wool growth. Several potential gene families might participate in hair growth regulation. Proteomic analysis also indentified hundreds of differentially expressed proteins.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-014-0144-1) contains supplementary material, which is available to authorized users.

Abstract 1075: Steroid receptor reprogramming of the chromatin landscape: crosstalk at the genomic level.

Abstract Crosstalk between the estrogen receptor (ER) and the glucocorticoid receptor (GR) plays an important role in controlling many cellular processes. Physiological interactions between ER and GR are not only important for the development of certain tissues, such as the uterus and bone, but also may play an important role in breast cancer. Recent studies have shown that the GR and ER status in breast cancer is a significant factor for determining the outcome of the disease. However, the mechanistic details defining the cellular interactions between ER and GR are poorly understood. Since the regulation of receptor binding to response elements controls the transcriptional output in response to hormones, it is logical to suspect that co-treatment of cells with corticosteroids and estradiol would have an effect on the genome-wide binding landscapes for GR and ER. Therefore, using chromatin immunoprecipitation followed by high-throughput sequencing we investigated the changes in genome-wide binding of ER and GR upon co-activation and revealed that there is global re-arrangement of steroid receptor binding. Furthermore, we unveiled a novel mechanism dictating the molecular interplay between ER and GR. Genome-wide sequencing of DnaseI hypersensitive sites upon induction of GR shows that GR facilitates selective access of ER to specific sites in the genome by maintaining an accessible configuration at these response elements. In addition, activation of ER can affect chromatin structure at novel GR binding sites, resulting in a new class of GR binding elements. Further studies show that at the sites where ER binding is facilitated by GR, binding to these newly accessible sites is not dependent on the direct binding of ER to its response element. Instead ER is brought to these sites through interactions with other factors, such as AP1. Overall, these studies define genome level interactions between ER and GR whereby the activation of multiple steroid receptors has a dramatic impact on controlling which regulatory elements are accessible to each receptor. The unveiling of this mechanism is important for understanding the molecular interplay between ER and GR in development and in cancer and may represent a general mechanism for crosstalk between receptors. Citation Format: Tina B. Miranda, Ty C. Voss, Myong-Hee Sung, Songjoon Baek, Sam John, Mary Hawkins, Lars Grontved, R. Louis Schiltz, Gordon L. Hager. Steroid receptor reprogramming of the chromatin landscape: crosstalk at the genomic level. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1075. doi:10.1158/1538-7445.AM2013-1075

Up-regulation of insulin binding in fish skeletal muscle by high insulin levels

The effects of insulin titres on regulation of receptor binding were studied in several fish species. Insulin receptors were semi-purified by affinity chromatography (WGA-agarose) from skeletal muscle of carp, brown trout and rainbow trout that had been subjected to increases in insulinemia produced either by arginine injection, food administration, or adaptation to an experimental diet (extruded diet with high-digestibility carbohydrates). Arginine injection provoked acute hyper-insulinemia in both carp and trout. Specific binding of insulin to the skeletal muscle was significantly increased 3 h after injection (from 5.8 ± 0.3 to 9.6 ± 0.9%/10 μ g protein in carp and from 0.8 ± 0.2 to 1.5 ± 0.4%/10 μ g in trout). The same effect was observed in carp liver preparations (from 6.0 ± 0.75 to 9.9 ± 1.25%/10 μ g ). No alterations in tyrosine kinase activity of the receptors were detected in either carp or trout preparations: basal activities of the receptors were maintained ( 3100 ± 200 fmol P/fmol receptors/30 min and 3700 ± 400 fmol P/fmol receptors/30 min, in carp and trout, respectively), as were the percentage of stimulation over basal levels obtained by incubation with insulin ( 227 ± 25% and 160 ± 10% respectively). Food ingestion raised plasma insulin levels more steadily. Specific binding also increased in skeletal muscle preparations, especially in carp (from 5.7 ± 0.3 to 11 ± 1.7%/10 μ g at 4 h and 10 ± 0.7%/10 μ g at 8 h). Tyrosine kinase activity was maintained without significant changes. Rainbow trout adapted for 2 months to an extruded diet presented higher insulin titres and higher glycogen reserves in liver and muscle. Insulin binding to skeletal muscle preparations was also significantly increased (from 0.36 ± 0.02 to 0.77 ± 0.1%/10 μ g ), as was tyrosine kinase activity (from 132 ± 4% to 156 ± 6%, without alterations in the basal activity). Results showed that fish can respond to both acute and maintained increases in insulinemia by increasing the number of insulin receptors. Tyrosine kinase activity, in contrast, is only modified after long-term adaptation.

Initial detection of [ 3H]clonidine binding to solubilized rat brainα 2-adrenergic receptors: regulation by guanine nucleotides

α 2-adrenergic receptors labeled by [ 3H]clonidine (α 2-antagonist) can be solubilized from the rat brain with a zwitterionic detergent, 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS). CHAPS-solubilized receptors have the same characteristics of membrane-boundα 2-receptors in the brain, and the regulation of receptor binding by guanine nucleotides is retained in the soluble state.

Solubilized Adenosine Receptors in the Brain: Regulation of Guanine Nucleotides

Adenosine receptors associated with a reduction of adenylate cyclase and labeled by tritium-labeled cyclohexyladenosine can be solubilized from brain membranes with sodium cholate. Regulation of receptor binding by guanine nucleotides is retained in the soluble state. Influences of cations observed in membrane preparations of adenosine receptors are no longer detected with the solubilized receptors. The apparent retention of a complex of receptors and guanosine triphosphate binding but not cation binding protein in the soluble state may permit a molecular analysis of receptor regulation.