Nuclear Receptor Research最新文献_第2页

A Comprehensive Analysis and Prediction of Sub-Cellular Localization of Human Nuclear Receptors 人核受体亚细胞定位的综合分析与预测

Nuclear Receptor Research Pub Date : 2018-06-04 DOI: 10.11131/2018/101324

Samatha Mathew, Keshav Thakur, Sudhir Kumar, A. Yende, Shashi Singh, A. K. Dash, R. Tyagi

{"title":"A Comprehensive Analysis and Prediction of Sub-Cellular Localization of Human Nuclear Receptors","authors":"Samatha Mathew, Keshav Thakur, Sudhir Kumar, A. Yende, Shashi Singh, A. K. Dash, R. Tyagi","doi":"10.11131/2018/101324","DOIUrl":"https://doi.org/10.11131/2018/101324","url":null,"abstract":"The Nuclear Receptor (NR) superfamily comprises of conserved ligand-modulated intracellular transcription factors which in the presence of their cognate ligands activate a plethora of signaling networks, thereby commencing their respective transcription functions. All NRs are nuclear when liganded or active. However, their localization may differ between nucleus and cytoplasm when unliganded or inactive. NRs control a majority of physiological processes in body ranging from metabolism to reproduction and development. Hitherto, in case of humans, 48 NRs have been identified which are localized either in cytosolic, nuclear or both compartments of the cell. Sub-cellular localization of proteins has great relevance in relation to their function. However, specific sub-cellular localization patterns of human NRs are clouded with ambiguity and are mostly ridden with controversy, with only a few of them being well-studied and established under specific physiological conditions. In the present study, we attempted to bridge the gap and attempted to draw conclusions in relation to sub-cellular localization of human NRs based on published experimental data and by in-silico prediction methods. This comprehensive analysis may not only be useful to draw conclusions on their control of physiological processes but may also open new avenues towards understanding of the molecular basis of NR-mediated diseases attributed to their mislocalization and malfunctioning.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43574545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Biphasic hCAR Inhibition-Activation by Two Aminoazo Liver Carcinogens 双相hCAR抑制-两种氨基偶氮肝癌物质的激活

Nuclear Receptor Research Pub Date : 2018-02-28 DOI: 10.11131/2018/101321

K. Bogen

{"title":"Biphasic hCAR Inhibition-Activation by Two Aminoazo Liver Carcinogens","authors":"K. Bogen","doi":"10.11131/2018/101321","DOIUrl":"https://doi.org/10.11131/2018/101321","url":null,"abstract":"Detailed dose-response data recently archived by the National Center for Biotechnology Information (NCBI) identified 853 human CAR (hCAR) agonists by quantitative high-throughput screening (qHTS) assays applied to >9,000 chemicals tested at ≥14 concentrations using n = 3–48 replicates. By re-examining NCBI data on 746 agonists with replicate data sets each satisfying additional quality criteria, ∼95% had average values of agonist-specific Hill-model slopes estimated by NCBI that exceed 1 (i.e., exhibited an overall sublinear low-dose dose-response), and two unambiguously biphasic hCAR inhibitor-agonists were identified, 4-aminoazobenzene (n = 37) and ortho-aminoazotoluene (n = 3), both of which also cause rodent liver tumors. Although evidently rare among hCAR agonists, such biphasic responses add to evidence that nuclear receptors can exhibit complex patterns of low-dose response, consistent with previous observations and theoretical predictions for endpoints governed by ultrasensitive molecular switches. The pronounced biphasic hCAR response pattern observed for 4-aminoazobenzene is particularly noteworthy insofar as it was identified with statistical power that exceeds that of most if not all other receptor-mediated biphasic cellular responses to any single-chemical exposure reported to date.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46677671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

The Role of Glucocorticoid Receptors in Podocytes and Nephrotic Syndrome. 糖皮质激素受体在足细胞和肾病综合征中的作用。

Nuclear Receptor Research Pub Date : 2018-01-01 Epub Date: 2018-04-24 DOI: 10.11131/2018/101323

Xuan Zhao, Daw-Yang Hwang, Hung-Ying Kao

{"title":"The Role of Glucocorticoid Receptors in Podocytes and Nephrotic Syndrome.","authors":"Xuan Zhao, Daw-Yang Hwang, Hung-Ying Kao","doi":"10.11131/2018/101323","DOIUrl":"https://doi.org/10.11131/2018/101323","url":null,"abstract":"Glucocorticoid receptor (GC), a founding member of the nuclear hormone receptor superfamily, is a glucocorticoid-activated transcription factor that regulates gene expression and controls the development and homeostasis of human podocytes. Synthetic glucocorticoids are the standard treatment regimens for proteinuria (protein in the urine) and nephrotic syndrome (NS) caused by kidney diseases. These include minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) or subsequent complications due to diabetes mellitus or HIV infection. However, unwanted side effects and steroid-resistance remain major issues for their long-term use. Furthermore, the mechanism by which glucocorticoids elicit their renoprotective activity in podocyte and glomeruli is poorly understood. Podocytes are highly differentiated epithelial cells that contribute to the integrity of kidney glomerular filtration barrier. Injury or loss of podocytes leads to proteinuria and nephrotic syndrome. Recent studies in multiple experimental models have begun to explore the mechanism of GC action in podocytes. This review will discuss progress in our understanding of the role of glucocorticoid receptor and glucocorticoids in podocyte physiology and their renoprotective activity in nephrotic syndrome.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11131/2018/101323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36665724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Glucocorticoid Receptor and Adipocyte Biology. 糖皮质激素受体与脂肪细胞生物学。

Nuclear Receptor Research Pub Date : 2018-01-01 DOI: 10.32527/2018/101373

Rebecca A Lee, Charles A Harris, Jen-Chywan Wang

{"title":"Glucocorticoid Receptor and Adipocyte Biology.","authors":"Rebecca A Lee, Charles A Harris, Jen-Chywan Wang","doi":"10.32527/2018/101373","DOIUrl":"https://doi.org/10.32527/2018/101373","url":null,"abstract":"Glucocorticoids are steroid hormones that play a key role in metabolic adaptations during stress, such as fasting and starvation, in order to maintain plasma glucose levels. Excess and chronic glucocorticoid exposure, however, causes metabolic syndrome including insulin resistance, dyslipidemia, and hyperglycemia. Studies in animal models of metabolic disorders frequently demonstrate that suppressing glucocorticoid signaling improves insulin sensitivity and metabolic profiles. Glucocorticoids convey their signals through an intracellular glucocorticoid receptor (GR), which is a transcriptional regulator. The adipocyte is one cell type that contributes to whole body metabolic homeostasis under the influence of GR. Glucocorticoids' functions on adipose tissues are complex. Depending on various physiological or pathophysiological states as well as distinct fat depots, glucocorticoids can either increase or decrease lipid storage in adipose tissues. In rodents, glucocorticoids have been shown to reduce the thermogenic activity of brown adipocytes. However, in human acute glucocorticoid exposure, glucocorticoids act to promote thermogenesis. In this article, we will review the recent studies on the mechanisms underlying the complex metabolic functions of GR in adipocytes. These include studies of the metabolic outcomes of adipocyte specific GR knockout mice and identification of novel GR primary target genes that mediate glucocorticoid action in adipocytes.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.32527/2018/101373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36578503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 52

Structural and Dynamic Elucidation of a Non-acid PPARγ Partial Agonist: SR1988. 非酸性PPARγ部分激动剂SR1988的结构和动力学解析。

Nuclear Receptor Research Pub Date : 2018-01-01 DOI: 10.11131/2018/101350

Rebecca L Frkic, Benjamin S Chua, Youseung Shin, Bruce D Pascal, Scott J Novick, Theodore M Kamenecka, Patrick R Griffin, John B Bruning

{"title":"Structural and Dynamic Elucidation of a Non-acid PPARγ Partial Agonist: SR1988.","authors":"Rebecca L Frkic, Benjamin S Chua, Youseung Shin, Bruce D Pascal, Scott J Novick, Theodore M Kamenecka, Patrick R Griffin, John B Bruning","doi":"10.11131/2018/101350","DOIUrl":"https://doi.org/10.11131/2018/101350","url":null,"abstract":"Targeting peroxisome proliferator-activated receptor γ (PPARγ) by synthetic compounds has been shown to elicit insulin sensitising properties in type 2 diabetics. Treatment with a class of these compounds, the thiazolidinediones (TZDs), has shown adverse side effects such as weight gain, fluid retention, and congestive heart failure. This is due to their full agonist properties on the receptor, where a number of genes are upregulated beyond normal physiological levels. Lessened transactivation of PPARγ by partial agonists has proved beneficial in terms of reducing side effects, while still maintaining insulin sensitising properties. However, some partial agonists have been associated with unfavourable pharmacokinetic profiles due to their acidic moieties, often causing partitioning to the liver. Here we present SR1988, a new partial agonist with favourable non-acid chemical properties. We used a combination of X-ray crystallography and hydrogen/deuterium exchange (HDX) to elucidate the structural basis for reduced activation of PPARγ by SR1988. This structural analysis reveals a mechanism that decreases stabilisation of the AF2 coactivator binding surface by the ligand.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37086576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Regulation of Microbiota by Vitamin D Receptor: A Nuclear Weapon in Metabolic Diseases. 维生素 D 受体对微生物群的调节：代谢性疾病中的核武器

Nuclear Receptor Research Pub Date : 2018-01-01 Epub Date: 2018-08-09 DOI: 10.11131/2018/101377

Danika Bakke, Ishita Chatterjee, Annika Agrawal, Yang Dai, Jun Sun

引用次数: 0

The Nuclear Receptor Field: A Historical Overview and Future Challenges. 核受体领域：历史回顾与未来挑战。

Nuclear Receptor Research Pub Date : 2018-01-01 Epub Date: 2018-07-26 DOI: 10.11131/2018/101320

Gisela I Mazaira, Nadia R Zgajnar, Cecilia M Lotufo, Cristina Daneri-Becerra, Jeffrey C Sivils, Olga B Soto, Marc B Cox, Mario D Galigniana

引用次数: 0

PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma. PPARs:哮喘气道炎症的关键调节因子和潜在的治疗靶点。

Nuclear Receptor Research Pub Date : 2018-01-01 Epub Date: 2017-12-11 DOI: 10.11131/2018/101306

Asoka Banno, Aravind T Reddy, Sowmya P Lakshmi, Raju C Reddy

{"title":"PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma.","authors":"Asoka Banno, Aravind T Reddy, Sowmya P Lakshmi, Raju C Reddy","doi":"10.11131/2018/101306","DOIUrl":"https://doi.org/10.11131/2018/101306","url":null,"abstract":"Asthma affects approximately 300 million people worldwide, significantly impacting quality of life and healthcare costs. While current therapies are effective in controlling many patients' symptoms, a large number continue to experience exacerbations or treatment-related adverse effects. Alternative therapies are thus urgently needed. Accumulating evidence has shown that the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors, comprising PPARα, PPARβ/δ, and PPARγ, is involved in asthma pathogenesis and that ligand-induced activation of these receptors suppresses asthma pathology. PPAR agonists exert their anti-inflammatory effects primarily by suppressing pro-inflammatory mediators and antagonizing the pro-inflammatory functions of various cell types relevant to asthma pathophysiology. Experimental findings strongly support the potential clinical benefits of PPAR agonists in the treatment of asthma. We review current literature, highlighting PPARs' key role in asthma pathogenesis and their agonists' therapeutic potential. With additional research and rigorous clinical studies, PPARs may become attractive therapeutic targets in this disease.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.11131/2018/101306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35837096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 57

Non-Mammalian Nuclear Receptors: From Evolution to Human Disease. 非哺乳动物核受体:从进化到人类疾病。

Nuclear Receptor Research Pub Date : 2018-01-01 DOI: 10.11131/2018/101366

Chris R Gissendanner, William S Baldwin, Marcel J M Schaaf

{"title":"Non-Mammalian Nuclear Receptors: From Evolution to Human Disease.","authors":"Chris R Gissendanner, William S Baldwin, Marcel J M Schaaf","doi":"10.11131/2018/101366","DOIUrl":"https://doi.org/10.11131/2018/101366","url":null,"abstract":"In 1964, Ulrich Clever published a landmark paper on the actions of 20-hydroxyecdysone (20E), the hormone that regulates molting and metamorphosis in insects. Based on the puﬃng activity of Chironomus tentans salivary gland polytene chromosomes, Clever was able to establish a pattern of gene activation in response to 20E A decade later, Michael Ashburner, utiliz-ing Drosophila melanogaster salivary gland polytene chromosomes, established a formalized model (the “Ashburner Model”) where 20E, bound to its receptor, activates a set of primary (“early”) target genes. The products of these genes, in turn, repress their own expression, and activate the transcription of secondary (“late”) target genes that control metamorphosis [2]. Subsequently, it was shown that the receptor for 20E, EcR, was an insect member of the nuclear receptor superfamily, and EcR, along with its heterodimer partner Usp (homolog of RXR), bind 20E and activate a set of early target genes at the onset of metamorphosis 4]. Additionally, many of the early gene products were also nuclear receptors that regulated the transcription of the secondary late genes Thus, the fruit ﬂy as an invertebrate model system for studying nuclear receptor signaling was established. The regulation of metamorphosis, in association with powerful fruit ﬂy genetics, became an important system for deciphering the mechanisms of nuclear receptor action, and subsequent studies demonstrated the utility that","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36494116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PPARδ, a Potential Therapeutic Target for Heart Disease. PPARδ，心脏病的潜在治疗靶点。

Nuclear Receptor Research Pub Date : 2018-01-01 Epub Date: 2018-10-30 DOI: 10.32527/2018/101375

Qinglin Yang, Qinqiang Long

引用次数: 0