scholarly journals Expression of cellular retinoic acid-binding protein I and II (CRABP I and II) in embryonic mouse hearts treated with retinoic acid.

2011 ◽  
Vol 58 (1) ◽  
Author(s):  
Emilia Stachurska ◽  
Agnieszka Loboda ◽  
Justyna Niderla-Bielińska ◽  
Małgorzata Szperl ◽  
Michał Juszyński ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Heart Development ◽  
Binding Proteins ◽  
Time Window ◽  
Endocardial Cushions ◽  
Western Blots ◽  
Embryonic Mouse ◽  
Crabp I ◽  
Retinoic Acid Binding Proteins ◽  
Crabp Ii

Cellular retinoic acid binding proteins are considered to be involved in retinoic acid (RA) signaling pathways. Our aim was to compare the expression and localization of cellular retinoic acid binding proteins I and II (CRABP I and II) in embryonic mouse hearts during normal development and after a single teratogenic dose of RA. Techniques such as real-time PCR, RT-PCR, Western blots and immunostaining were employed to examine hearts from embryos at 9-17 dpc. RA treatment at 8.5dpc affects production of CRABP I and II in the heart in the 48-h period. Changes in expression of mRNA for retinaldehyde dehydrogenase II (Raldh2), Crabp1 and Crabp2 genes also occur within the same time window (i.e. 10-11dpc) after RA treatment. In the embryonic control heart these proteins are localized in groups of cells within the outflow tract (OT), and the atrioventricular endocardial cushions. A gradient of labeling is observed with CRABP II but not for CRABP I along the myocardium of the looped heart at 11 dpc; this gradient is abolished in hearts treated with RA, whereas an increase of RALDH2 staining has been observed at 10 dpc in RA-treated hearts. Some populations of endocardial endothelial cells were intensively stained with anti-CRABP II whereas CRABP I was negative in these structures. These results suggest that CRABP I and II are independently regulated during heart development, playing different roles in RA signaling, essential for early remodeling of the heart tube and alignment of the great arteries to their respective ventricles.

Structures of cellular retinoic acid binding proteins I and II in complex with synthetic retinoids

1999 ◽  
Vol 55 (11) ◽  
pp. 1850-1857 ◽  
Author(s):  
Barnali Neel Chaudhuri ◽  
Gerard J. Kleywegt ◽  
Isabelle Broutin-L'Hermite ◽  
Terese Bergfors ◽  
Hans Senn ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Binding Proteins ◽  
Specific Protein ◽  
Binding Affinities ◽  
Cellular Processes ◽  
Crabp I ◽  
Retinoid Binding Proteins ◽  
Retinoic Acid Binding Proteins ◽  
Crabp Ii ◽  
Kinetics Of

Retinoids play important roles in diverse cellular processes including growth, cell differentiation and vision. Many natural and synthetic retinoids are used as drugs in dermatology and oncology. A large amount of data has been accumulated on the cellular activity of different synthetic retinoids. They are stabilized and transported inside the cell cytoplasm by binding and transport proteins, such as cellular retinol-binding proteins and cellular retinoic acid binding proteins (CRABPs). The structures of human CRABP II in complex with two different synthetic retinoids, Ro13-6307 and Ro12-7310 (at 2.1 and 2.0 Å resolution, respectively) and of bovine CRABP I in complex with a retinobenzoic acid, Am80 (at 2.8 Å resolution) are described. The binding affinities of human CRABP I and II for the retinoids studied here have been determined. All these compounds have comparable binding affinities (nanomolar range) for both CRABPs. Apart from the particular interactions of the carboxylate group of the retinoids with specific protein groups, each structure reveals characteristic interactions. Studying the atomic details of the interaction of retinoids with retinoid-binding proteins facilitates the understanding of the kinetics of retinoid trafficking inside the cytoplasm.

scholarly journals Selective Cooperation between Fatty Acid Binding Proteins and Peroxisome Proliferator-Activated Receptors in Regulating Transcription

2002 ◽  
Vol 22 (14) ◽  
pp. 5114-5127 ◽  
Author(s):  
Nguan-Soon Tan ◽  
Natacha S. Shaw ◽  
Nicolas Vinckenbosch ◽  
Peng Liu ◽  
Rubina Yasmin ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Fatty Acid ◽  
Binding Proteins ◽  
Lipid Binding ◽  
Fatty Acid Binding Proteins ◽  
Peroxisome Proliferator ◽  
Fatty Acid Binding ◽  
Peroxisome Proliferator Activated Receptors ◽  
Retinoic Acid Binding Proteins ◽  
Crabp Ii

ABSTRACT Lipophilic compounds such as retinoic acid and long-chain fatty acids regulate gene transcription by activating nuclear receptors such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptors (PPARs). These compounds also bind in cells to members of the family of intracellular lipid binding proteins, which includes cellular retinoic acid-binding proteins (CRABPs) and fatty acid binding proteins (FABPs). We previously reported that CRABP-II enhances the transcriptional activity of RAR by directly targeting retinoic acid to the receptor. Here, potential functional cooperation between FABPs and PPARs in regulating the transcriptional activities of their common ligands was investigated. We show that adipocyte FABP and keratinocyte FABP (A-FABP and K-FABP, respectively) selectively enhance the activities of PPARγ and PPARβ, respectively, and that these FABPs massively relocate to the nucleus in response to selective ligands for the PPAR isotype which they activate. We show further that A-FABP and K-FABP interact directly with PPARγ and PPARβ and that they do so in a receptor- and ligand-selective manner. Finally, the data demonstrate that the presence of high levels of K-FABP in keratinocytes is essential for PPARβ-mediated induction of differentiation of these cells. Taken together, the data establish that A-FABP and K-FABP govern the transcriptional activities of their ligands by targeting them to cognate PPARs in the nucleus, thereby enabling PPARs to exert their biological functions.

Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 267-282 ◽  
Author(s):  
E. Ruberte ◽  
V. Friederich ◽  
P. Chambon ◽  
G. Morriss-Kay
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Binding Proteins ◽  
Binding Protein ◽  
Retinoic Acid Receptors ◽  
Type I ◽  
Crabp I ◽  
Retinoid Binding Proteins ◽  
Crabp Ii

We have studied the transcript distribution of the retinoic acid receptors (RARs) and the cytoplasmic retinoid binding proteins during embryonic development of the mouse nervous system. Of the three retinoic acid receptors, only RAR-gamma was not expressed in developing neural structures. RAR-beta and RAR-alpha both showed rostral limits of expression in the medulla oblongata equivalent to their patterns of expression in the neuroepithelium of the early hindbrain neural tube. Within their expression domains in the spinal cord and brain, RAR-alpha was ubiquitously expressed, whereas RAR-beta transcripts showed very specific patterns of expression, suggesting that this receptor is involved in mediating retinoic acid-induced gene expression in relation to the development of specific neural structures or pathways. The cytoplasmic binding proteins, cellular retinoic acid binding proteins type I and II (CRABP I and CRABP II) and cellular retinol binding protein type I (CRBP I), were widely distributed in developing neural structures. Their differential spatiotemporal patterns of expression suggest that fine regional control of availability of retinoic acid (RA) to the nuclear receptors plays an important role in organization and differentiation of the nervous system. For instance, expression of CRABP I in the migrating cells that give rise to the olivary and pontine nuclei, which develop abnormally in conditions of retinoid excess, is consistent with observations from a variety of other systems indicating that CRABP I limits the access of RA to the nuclear receptors in normal physiological conditions. Similarly, expression of CRBP I in the choroid plexuses, which develop abnormally in conditions of vitamin A deficiency, is consistent with observations indicating that this binding protein mediates the synthesis of RA in tissues requiring high levels of RA for their normal developmental programme. RAR-beta and CRABP II, which are both RA-inducible, were coexpressed with CRBP I in the choroid plexus and in many other sites, perhaps reflecting the fact that all three genes are RA-inducible. The function of CRABP II is not well understood; its domains of expression showed overlaps with both CRABP I and CRBP I.

Abstract 241: Retinoic Acid Promotes Metabolic Maturation of Human Embryonic Stem Cell-derived Cardiomyocytes

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Shumei Miao ◽  
Xing Fang ◽  
Xiaoxiao Wang ◽  
Lingqun Ye ◽  
Jingsi Yang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Retinoic Acid ◽  
Heart Development ◽  
Drug Testing ◽  
Disease Modeling ◽  
Time Window ◽  
Embryonic Stem ◽  
Early Time ◽  
Control Group ◽  
Cardiomyocyte Differentiation

Cardiomyocytes differentiated from human embryonic stem cells (hESCs) represent a promising cell source for heart repair, disease modeling and drug testing. However, improving the differentiation efficiency and maturation of hESC-derived cardiomyocytes (hESC-CMs) is still a major concern. Retinoic acid (RA) signaling plays multiple roles in heart development, and studies on RA can provide clues for understanding cardiomyocyte differentiation and maturation. In this study, we studied the roles of RA during cardiomyocyte differentiation and maturation, systematically. After adding RA at different stages of cardiomyocyte differentiation, we compared the efficiency of differentiation by quantitative real-time PCR and flow cytometry. We found that RA treatment at the lateral mesoderm stage (days 2-4) significantly improved cardiomyocyte differentiation, as evidenced by the upregulation of TNNT2, NKX2.5 and MYH6 on day 10 of differentiation. In addition, flow cytometry showed that the proportion of differentiated cardiomyocytes in the RA-treated group was significantly higher than that in control group. Furthermore, RA was added at different time intervals after purification to induce cardiomyocyte maturation. Our results demonstrated that RA treatment on days 15-20 increased cardiomyocyte area, sarcomere length, multinucleation and mitochondrial copy number, and promoted RNA splicing switch. Importantly, RA-treated cardiomyocytes showed decreased glycolysis and enhanced mitochondrial oxidative phosphorylation, with the increased utilization of fatty acid and exogenous pyruvate but not glutamine. In conclusion, our data indicated that RA treatment at an early time window (days 2-4) promotes the efficiency of cardiomyocyte differentiation and that RA treatment post beating (days 15-20) promotes cardiomyocyte metabolic maturation. The biphasic effects of RA provide new insights for improving cardiomyocyte differentiation and quality.

scholarly journals Novel Fluorescence Competition Assay for Retinoic Acid Binding Proteins

2018 ◽  
Vol 9 (12) ◽  
pp. 1297-1300 ◽  
Author(s):  
Charles W. E. Tomlinson ◽  
David R. Chisholm ◽  
Roy Valentine ◽  
Andrew Whiting ◽  
Ehmke Pohl
Keyword(s):  
Retinoic Acid ◽  
Binding Proteins ◽  
Competition Assay ◽  
Retinoic Acid Binding Proteins
Sign in / Sign up

Export Citation Format

Share Document