Nuclear Receptor Research最新文献_第5页

Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity 外源受体介导的肠道屏障功能和先天免疫调节

Nuclear Receptor Research Pub Date : 2016-05-07 DOI: 10.11131/2016/101199

H. S. Ranhotra, K. Flannigan, Martina Brave, Subhajit Mukherjee, D. Lukin, S. Hirota, S. Mani

引用次数: 32

Mycotoxins and Nuclear Receptors: A Still Underexplored Issue 真菌毒素和核受体:一个仍未充分探讨的问题

Nuclear Receptor Research Pub Date : 2016-02-12 DOI: 10.11131/2016/101204

C. Dall’Asta

引用次数: 5

Regulation of Drug Disposition Gene Expression in Pregnant Mice with Car Receptor Activation. Car受体激活对妊娠小鼠药物处置基因表达的调控。

Nuclear Receptor Research Pub Date : 2016-02-07 DOI: 10.11131/2016/101193

A. Bright, G. Herrera-Garcia, Jamie E. Moscovitz, D. You, G. Guo, L. Aleksunes

{"title":"Regulation of Drug Disposition Gene Expression in Pregnant Mice with Car Receptor Activation.","authors":"A. Bright, G. Herrera-Garcia, Jamie E. Moscovitz, D. You, G. Guo, L. Aleksunes","doi":"10.11131/2016/101193","DOIUrl":"https://doi.org/10.11131/2016/101193","url":null,"abstract":"More than half of pregnant women use prescription medications in order to maintain both maternal and fetal health. The constitutive androstane receptor (Car) critically affects the disposition of chemicals by regulating the transcription of genes encoding metabolic enzymes and transporters. However, the effects of Car activation on chemical disposition during pregnancy are unclear. This study aims to determine the degree to which pregnancy alters the expression of drug metabolizing enzymes and transporters in response to the pharmacological activation of Car. To test this, pregnant C57BL/6 mice were administered IP doses of vehicle, or a potent Car agonist, TCPOBOP, on gestation days 14, 15 and 16. Hepatic mRNA and protein expression of Car target genes (phase I, II and transporters) were quantified on gestation day 17. Pregnancy-related changes, such as induction of Cyp2b10, Ugt1a1 and Sult1a1 and repression of Ugt1a6, Gsta1, Gsta2 and Mrp6, were observed. Interestingly, the induction of Cyp2b10, Gsta1, Gsta2 and Mrp2-4 mRNAs by TCPOBOP was attenuated in maternal livers suggesting that Car activation is impeded by the biochemical and/or physiological changes that occur during gestation. Taken together, these findings suggest that pregnancy and pharmacological activation of Car can differentially regulate the expression of drug metabolism and transport genes.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"63478720","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: 6

New Insights in the Role of Androgen-to-Estrogen Ratios, Specific Growth Factors and Bone Cell Microenvironment to Potentiate Prostate Cancer Bone Metastasis 雄激素雌激素比、特定生长因子和骨细胞微环境在前列腺癌骨转移中的作用的新认识

Nuclear Receptor Research Pub Date : 2015-12-31 DOI: 10.11131/2015/101186

E. McNerney, S. Oñate

{"title":"New Insights in the Role of Androgen-to-Estrogen Ratios, Specific Growth Factors and Bone Cell Microenvironment to Potentiate Prostate Cancer Bone Metastasis","authors":"E. McNerney, S. Oñate","doi":"10.11131/2015/101186","DOIUrl":"https://doi.org/10.11131/2015/101186","url":null,"abstract":"Prostate cancer progression to bone metastasis is an early event that remains dormant when the androgen ratio to estrogen is high. Only 40% of patients with bone metastasis and skeletal involvement survive past the first year. During andropause, changes in hormone ratios and nuclear receptor coregulator expression, in conjunction with crosstalk with fibroblast growth factors and bone stroma signaling pathways, reactivate the early metastasis. This review will provide insights into how this interplay induces changes in the osteolytic microenvironment to promote prostate cancer metastasis to the bone. While both AR and ER induce changes in the osteolytic microenvironment to promote bone metastasis, it is ERα overexpression that stimulates osteoblast differentiation, proliferation, osteoclast-mediated bone resorption, and the release of bone matrix factors. Loss of ERβ1 enhances VEGF expression and tumor cell survival through stimulation of osteoblast differentiation. Aberrant expression of FGFs and FGF receptors (FGFRs) initiates MAPK, PI3K, and PLCγ pathways, resulting in proliferation, dedifferentiation, angiogenesis and survival. The paracrine action of FGF10 may be required for bone metastasis reactivation due to interaction with bone stromal cells when E2/T ratio increases. This ratio change provides a potential mechanism for estrogen signal activation when prostate cancer cells express ERα in the presence of bone stromal cells, resulting in ERα predominance over the AR activity due to changes in coactivator/corepressor recruitment by ERα when circulating androgens are reduced during hormonal deprivation therapies.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"63478698","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: 1

Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism 视黄酸相关孤儿受体(RORs):在免疫、发育、昼夜节律和代谢中的调节功能

Nuclear Receptor Research Pub Date : 2015-12-16 DOI: 10.11131/2015/101185

D. Cook, Hong Soon Kang, A. Jetten

引用次数: 136

Pan-cancer analyses of the nuclear receptor superfamily. 核受体超家族的泛癌分析。

Nuclear Receptor Research Pub Date : 2015-12-01 Epub Date: 2015-12-15 DOI: 10.11131/2015/101182

Mark D Long, Moray J Campbell

{"title":"Pan-cancer analyses of the nuclear receptor superfamily.","authors":"Mark D Long, Moray J Campbell","doi":"10.11131/2015/101182","DOIUrl":"https://doi.org/10.11131/2015/101182","url":null,"abstract":"Nuclear receptors (NR) act as an integrated conduit for environmental and hormonal signals to govern genomic responses, which relate to cell fate decisions. We review how their integrated actions with each other, shared co-factors and other transcription factors are disrupted in cancer. Steroid hormone nuclear receptors are oncogenic drivers in breast and prostate cancer and blockade of signaling is a major therapeutic goal. By contrast to blockade of receptors, in other cancers enhanced receptor function is attractive, as illustrated initially with targeting of retinoic acid receptors in leukemia. In the post-genomic era large consortia, such as The Cancer Genome Atlas, have developed a remarkable volume of genomic data with which to examine multiple aspects of nuclear receptor status in a pan-cancer manner. Therefore to extend the review of NR function we have also undertaken bioinformatics analyses of NR expression in over 3000 tumors, spread across six different tumor types (bladder, breast, colon, head and neck, liver and prostate). Specifically, to ask how the NR expression was distorted (altered expression, mutation and CNV) we have applied bootstrapping approaches to simulate data for comparison, and also compared these NR findings to 12 other transcription factor families. Nuclear receptors were uniquely and uniformly downregulated across all six tumor types, more than predicted by chance. These approaches also revealed that each tumor type had a specific NR expression profile but these were most similar between breast and prostate cancer. Some NRs were down-regulated in at least five tumor types (e.g. NR3C2/MR and NR5A2/LRH-1)) whereas others were uniquely down-regulated in one tumor (e.g. NR1B3/RARG). The downregulation was not driven by copy number variation or mutation and epigenetic mechanisms maybe responsible for the altered nuclear receptor expression.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869537/pdf/nihms765395.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34397876","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: 42

Peroxisome Proliferator-Activated Receptors: Features, Functions, and Future 过氧化物酶体增殖体激活受体:特征、功能和未来

Nuclear Receptor Research Pub Date : 2015-11-25 DOI: 10.11131/2015/101188

J. Youssef, M. Badr

引用次数: 10

Activation of Nuclear Receptors RAR, RXR, and LXR Does Not Reduce Cuprizone-Induced Demyelination in Mice 激活核受体RAR, RXR和LXR不会减少铜酮诱导的小鼠脱髓鞘

Nuclear Receptor Research Pub Date : 2015-06-26 DOI: 10.11131/2015/101163

Davina Kruczek, T. Clarner, C. Beyer, M. Kipp, J. Mey

{"title":"Activation of Nuclear Receptors RAR, RXR, and LXR Does Not Reduce Cuprizone-Induced Demyelination in Mice","authors":"Davina Kruczek, T. Clarner, C. Beyer, M. Kipp, J. Mey","doi":"10.11131/2015/101163","DOIUrl":"https://doi.org/10.11131/2015/101163","url":null,"abstract":"Experiments with animal models of multiple sclerosis have shown that the expression of retinoid X receptors (RXR) increases during demyelination and that RXR is involved in the regulation of remyelination. After ligand binding RXRs form heterodimeric transcription factors with other nuclear receptor (NR) families including the retinoic acid receptors (RAR) and liver X receptors (LXR). We tested whether activation of these nuclear receptor complexes reduces pathological demyelination using the cuprizone mouse model. Cuprizone, which causes oligodendrocyte degeneration, was given for three weeks as a food additive. For the activation of nuclear receptors mice were treated with daily i.p. injections of agonists for RXR (9-cis RA), RAR (all-trans RA), and LXR (T0901317). Myelin status, oligodendrocyte survival, astrogliosis, microglial activation, and axon density were monitored with immunohistochemistry and evaluated quantitatively. Three weeks of cuprizone feeding caused severe demyelination and significantly raised the number of Iba1 immunoreactive microglia cells in the caudal corpus callosum. This increase of microglia activity was reduced with 9-cis RA treatment but was enhanced with all-trans RA and was not affected by T0901317. Nuclear receptor activation did not influence the degree of demyelination, oligodendrocyte survival, astrogliosis, or axonal preservation. We conclude that RXR activation, although affecting Iba1-positive microglia, does not protect oligodendrocytes from cuprizone toxicity and does not induce compensatory mechanisms in the initial phase of demyelination.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"63478609","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

LXR Inhibits Proliferation of Human Breast Cancer Cells through the PI3K-Akt Pathway LXR通过PI3K-Akt通路抑制人乳腺癌细胞增殖

Nuclear Receptor Research Pub Date : 2015-01-05 DOI: 10.11131/2015/101154

Treska S. Hassan, A. Paniccia, V. Russo, K. Steffensen

引用次数: 10

New Insights into Orphan Nuclear Receptor SHP in Liver Cancer. 孤儿核受体SHP在肝癌中的新认识

Nuclear Receptor Research Pub Date : 2015-01-01 Epub Date: 2015-08-18 DOI: 10.11131/2015/101162

An Zou, Sarah Lehn, Nancy Magee, Yuxia Zhang

{"title":"New Insights into Orphan Nuclear Receptor SHP in Liver Cancer.","authors":"An Zou, Sarah Lehn, Nancy Magee, Yuxia Zhang","doi":"10.11131/2015/101162","DOIUrl":"https://doi.org/10.11131/2015/101162","url":null,"abstract":"Small heterodimer partner (SHP; NR0B2) is a unique orphan nuclear receptor (NR) that contains a putative ligand-binding domain but lacks a DNA-binding domain. SHP is a transcriptional corepressor affecting diverse metabolic processes including bile acid synthesis, cholesterol and lipid metabolism, glucose and energy homeostasis, and reproductive biology via interaction with multiple NRs and transcriptional factors (TFs). Hepatocellular carcinoma (HCC) is one of the most deadly human cancers worldwide with few therapeutic options and poor prognosis. Recently, it is becoming clear that SHP plays an antitumor role in the development of liver cancer. In this review, we summarize the most recent findings regarding the new SHP interaction partners, new structural insights into SHP's gene repressing activity, and SHP protein posttranslational modifications by bile acids. We also discuss the pleiotropic role of SHP in regulating cell proliferation, apoptosis, DNA methylation, and inflammation that are related to antitumor role of SHP in HCC. Improving our understanding of SHP's antitumor role in the development of liver cancer will provide new insights into developing novel treatments or prevention strategies. Future research will focus on developing more efficacious and specific synthetic SHP ligands for pharmaceutical applications in liver cancer and several metabolic diseases such as hypercholesterolemia, obesity, diabetes, and fatty liver disease.","PeriodicalId":30720,"journal":{"name":"Nuclear Receptor Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34118798","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: 22