Unknown,Transcriptomics,Genomics,Proteomics

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Microarray analysis indicates that vitamin A alters expression profiles of bovine intramuscular preadipocytes during adipogenesis

ABSTRACT: Beef marbling is caused by intramuscular deposition, and it is an economically important trait in the beef industry. Vitamin A (VA) is an important feed supplement for cattle, but it can hinder marbling if provided in excess. In cattle, VA forms various derivatives such as all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9cRA). Therefore, we investigated the genes involved in bovine intramuscular adipogenesis after VA treatment with ATRA and 9cRA. Differential gene expression levels were validated by microarray analysis in a clonal bovine intramuscular preadipocyte (BIP) cell line derived from the intramuscular adipose tissue of Japanese Black cattle. BIP cells were harvested six days after adipogenic stimulation with either 1 ?M ATRA, 1 ?M 9cRA, or nonretinoic acids control. The ATRA- and 9cRA-treated cells exhibited reduced transcription of genes involved in the circulatory system and muscle development compared with the no retinoic acid (RA) treatment. In addition, the ATRA- and 9cRA-treated cells exhibited increased transcription of genes involved in the immune system, protein kinase B signaling, and responses to various stimuli. These results demonstrate the lower expression of muscle development in ATRA- and 9cRA-treated BIP cells during adipogenesis. BIP cells were cultured according to previously reported methods (Aso et al. 1995, Mizoguchi et al. 2014). Confluent cultures were transferred to fresh Dulbecco’s modified Eagle’s medium, which contained 50 ng/mL insulin, 0.25 ?M dexamethasone, 5 mM octanoate, 10 mM acetic acid, 10% fetal bovine serum, 100 U/mL penicillin, and 100 ?g/mL streptomycin. The cells were cultured for up to 6 days and the medium was changed every 2 days. BIP cells were treated with ATRA (1 ?M), 9cRA (1 ?M), or they received no treatment (control).

ORGANISM(S): Bos taurus

SUBMITTER: Daiki Taniguchi

PROVIDER: E-GEOD-59166 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Haffez2017 - RAR interaction with synthetic analogues This model is described in the article: The molecular basis of the interactions between synthetic retinoic acid analogues and the retinoic acid receptors Hesham Haffez, David R. Chisholm, Roy Valentine, Ehmke Pohl, Christopher Redfern and Andrew Whiting MedChemComm Abstract: All-trans-retinoic acid (ATRA) and its synthetic analogues EC23 and EC19 direct cellular differentiation by interacting as ligands for the retinoic acid receptor (RARÎ±, Î² and Î³) family of nuclear receptor proteins. To date, a number of crystal structures of natural and synthetic ligands complexed to their target proteins have been solved, providing molecular level snap-shots of ligand binding. However, a deeper understanding of receptor and ligand flexibility and conformational freedom is required to develop stable and effective ATRA analogues for clinical use. Therefore, we have used molecular modelling techniques to define RAR interactions with ATRA and two synthetic analogues, EC19 and EC23, and compared their predicted biochemical activities to experimental measurements of relative ligand affinity and recruitment of coactivator proteins. A comprehensive molecular docking approach that explored the conformational space of the ligands indicated that ATRA is able to bind the three RAR proteins in a number of conformations with one extended structure being favoured. In contrast the biologically-distinct isomer, 9-cis-retinoic acid (9CRA), showed significantly less conformational flexibility in the RAR binding pockets. These findings were used to inform docking studies of the synthetic retinoids EC23 and EC19, and their respective methyl esters. EC23 was found to be an excellent mimic for ATRA, and occupied similar binding modes to ATRA in all three target RAR proteins. In comparison, EC19 exhibited an alternative binding mode which reduces the strength of key polar interactions in RARÎ±/Î³ but is well-suited to the larger RARÎ² binding pocket. In contrast, docking of the corresponding esters revealed the loss of key polar interactions which may explain the much reduced biological activity. Our computational results were complemented using an in vitro binding assay based on FRET measurements, which showed that EC23 was a strongly binding, pan-agonist of the RARs, while EC19 exhibited specificity for RARÎ², as predicted by the docking studies. These findings can account for the distinct behaviour of EC23 and EC19 in cellular differentiation assays, and additionally, the methods described herein can be further applied to the understanding of the molecular basis for the selectivity of different retinoids to RARÎ±, Î² and Î³. This model is hosted on BioModels Database and identified by: BIOMD0000000629. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:A rexinoid, targretin (TRG) and two retinoids, 9-cis retinoic acid (9cRA) and 4-hydroxyphenylretinamide (4HPR) were examined for their effects on gene expression in rat mammary gland, liver, and lung tissues. The chemopreventive effects of these agents have largely been attributed to their ability to interact with retinoic acid receptors (RAR) and/or retinoid X-receptors (RXR). TRG interacts with the RXR receptors. 9cRA interacts with both the RAR and RXR receptors, while 4HPR has a moderate affinity primarily for RAR gamma. Based on previously performed mammary chemoprevention studies, TRG (150mg/Kg diet), 9cRA (100 mg/Kg diet), and 4HPR (792 mg/Kg diet), were administrated to rats continually in their diet for 7 days. Tissue - and agent - specific expression differences were determined by comparing tissues from treated rats with those form rats administered a control diet. There were significantly more changes seen associated with TRG than 9cRA or 4HPR. Only a limited number of expression changes were found with 4HPR treatment. For each organ, TRG and 9cRA treated tissues clustered closely together, whereas 4HPR treated tissues clustered with the tissues from the control diet group. In contrast to 9cRA treatment, TRG treatment altered genes that involved fatty acid metabolism and modulation of various cytochromes P450 in the liver clearly demonstrating the very disparate nature of these two retinoids. These expression signatures could provide useful pharmacodynamic biomarkers for retinoidsâ treatment and chemoprevention. Experiment Overall Design: Agent : The 3 agents were obtained from NCI Chemical Repository (Bethesda, MD), Targretin, 9-cis retinoic acid, and 4-hydroxyphenylretinamide. Experiment Overall Design: Rat :Female Sprague-Dawley rats were used (Harlan Sprague-Dawley, Inc. Indianapolis, IN) Experiment Overall Design: Treatment: Starting at 100 days of age, the rats received treatment of TRG (60 mg/kg BW, gavage), 9cRA (100 mg/kg diet), or 4HPR (782 mg/kg diet) for 7 days. At the end of the 7-day treatment, normal mammary gland, liver and lung tissues were collected.

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Microarray analysis indicates that vitamin A alters expression profiles of bovine intramuscular preadipocytes during adipogenesis

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