All-trans retinoic acid-responsive genes identified in the human SH-SY5Y neuroblastoma cell line and their regulated expression in the nervous system of early embryos

2004 ◽  
Vol 385 (7) ◽  
Author(s):  
R.A. Merrill ◽  
J.M. Ahrens ◽  
M.E. Kaiser ◽  
K.S. Federhart ◽  
V.Y. Poon ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Cell Line ◽  
Human Cell ◽  
Rat Embryos ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Developing Rat

AbstractThe vitamin A metabolite, all-trans retinoic acid (atRA), is required for embryonic development. atRA binds to the nuclear retinoic acid receptors and regulates the transcription of specific target genes. In order to identify atRA-induced genes that play a role in neural development, a subtractive library was created from SH-SY5Y neuroblastoma cells, a human cell line that exhibits changes in cell adhesion and neurite outgrowth after exposure to the vitamin A acid. We report here the identification of 14 genes that are rapidly induced by atRA (retinoic acid induced in neurobIlastoma or RAINB), eight of which were previously not known to be atRA responsive (BTBD11, calmin, cyclin M2, ephrin B2, HOXD10, NEDD9, RAINB6 and tenascin R). mRNA regulation by atRA was confirmed in SHSY5Y cells by Northern blotting, and gene regulation was studied in additional human cell lines using the quantitative polymerase chain reaction. The majority of the atRA-responsive clones revealed in this screen are highly expressed in the nervous system of developing rat embryos. Further, the expression of several of these genes is perturbed in developing rat embryos exposed to excess atRA or conversely, deprived of sufficient retinoid during early development. We propose that a subset of these genes lie downstream of atRA and its receptors in the regulation of neurite outgrowth and cell adhesion in both neural and nonneural tissues within the developing embryo.

scholarly journals Hypertrophy of Adipose Tissues in Quail Embryos by in ovo Injection of All-Trans Retinoic Acid

2021 ◽  
Vol 12 ◽  
Author(s):  
Dong-Hwan Kim ◽  
Joonbum Lee ◽  
Sanggu Kim ◽  
Hyun S. Lillehoj ◽  
Kichoon Lee
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Marker Gene ◽  
Marker Genes ◽  
Health Issues ◽  
Fat Cell ◽  
In Ovo ◽  
Adipose Tissues ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Excessive adipose accretion causes health issues in humans and decreases feed efficiency in poultry. Although vitamin A has been known to be involved in adipogenesis, effects of all-trans retinoic acid (atRA), as a metabolite of vitamin A, on embryonic adipose development have not been studied yet. Avian embryos are developing in confined egg environments, which can be directly modified to study effects of nutrients on embryonic adipogenesis. With the use of quail embryos, different concentrations of atRA (0 M to 10 μM) were injected in ovo at embryonic day (E) 9, and adipose tissues were sampled at E14. Percentages of fat pad weights in embryo weights were significantly increased in the group injected with 300 nM of atRA. Also, among three injection time points, E5, E7, or E9, E7 showed the most significant increase in weight and percentage of inguinal fat at E14. Injection of atRA at E7 increased fat cell size in E14 embryos with up-regulation of pro-adipogenic marker genes (Pparγ and Fabp4) and down-regulation of a preadipocyte marker gene (Dlk1) in adipose tissues. These data demonstrate that atRA promotes hypertrophic fat accretion in quail embryos, implying important roles of atRA in embryonic development of adipose tissues.

scholarly journals All-Trans-Retinoic Acid Augments the Histopathological Outcome of Neuroinflammation and Neurodegeneration in Lupus-Prone MRL/lpr Mice

2016 ◽  
Vol 65 (2) ◽  
pp. 69-81 ◽  
Author(s):  
Michelle H. Theus ◽  
Joshua B. Sparks ◽  
Xiaofeng Liao ◽  
Jingjing Ren ◽  
Xin M. Luo
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Plasma Cells ◽  
Third Ventricle ◽  
Brain Regions ◽  
Systemic Autoimmune Disease ◽  
Negative Effects ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
The Central Nervous System

Recently, we demonstrated that treatment with all- trans-retinoic acid (tRA) induced a paradoxical effect on immune activation during the development of autoimmune lupus. Here, we further describe its negative effects on mediating neuroinflammation and neurodegeneration. Female MRL/lpr mice were orally administered tRA or VARA (retinol mixed with 10% tRA) from 6 to 14 weeks of age. Both treatments had a significant effect on brain weight, which correlated with histopathological evidence of focal astrogliosis, meningitis, and ventriculitis. Infiltration of CD138- and Iba1-positve immune cells was observed in the third ventricle and meninges of treated mice that co-labeled with ICAM-1, indicating their inflammatory nature. Increased numbers of circulating plasma cells, autoantibodies, and total IgG were also apparent. IgG and C3 complement deposition in these brain regions were also prominent as was focal astrogliosis surrounding the ventricular lining and meninges. Using Fluoro-Jade staining, we further demonstrate that neuroinflammation was accompanied by neurodegeneration in the cortex of treated mice compared with vehicle controls. These findings indicate that vitamin A exposure exacerbates the immunogenic environment of the brain during the onset of systemic autoimmune disease. Vitamin A may therefore compromise the immuno-privileged nature of the central nervous system under a predisposed immunogenic environment.

scholarly journals HPLC-MS/MS Shows That the Cellular Uptake of All-Trans-Retinoic Acid under Hypoxia Is Downregulated by the Novel Active Agent 5-Methoxyleoligin

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2048
Author(s):  
Armin Sebastian Guntner ◽  
Christian Doppler ◽  
Christian Wechselberger ◽  
David Bernhard ◽  
Wolfgang Buchberger
Keyword(s):  
Myocardial Infarction ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Cell Damage ◽  
Umbilical Vein ◽  
Active Agent ◽  
The Novel ◽  
Novel Therapy ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

All-trans-retinoic acid (atRA) is the essential derivative of vitamin A and is of interest due to its various biological key functions. As shown in the recent literature, atRA also plays a role in the failing heart during myocardial infarction, the leading cause of death globally. To date insufficient mechanistic information has been available on related hypoxia-induced cell damage and reperfusion injuries. However, it has been demonstrated that a reduction in cellular atRA uptake abrogates hypoxia-mediated cell and tissue damage, which may offer a new route for intervention. Consequently, in this study, the effect of the novel cardio-protective compound 5-methoxyleoligin (5ML) on cellular atRA uptake was tested in human umbilical-vein endothelial cells (HUVECs). For this purpose, a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to assess intra-cellular levels of the active substance and corresponding levels of vitamin A and its derivatives, including potential cis/trans isomers. This work also focused on light-induced isomerization and the stability of biological sample material to ensure sample integrity and avoid biased conclusions. This study provides evidence of the inhibitory effect of 5ML on cellular atRA uptake, a promising step toward a novel therapy for myocardial infarction.

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