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 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 Modulation of spontaneous B-cell differentiation in macroglobulinemia by retinoic acid

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2206-2210 ◽  
Author(s):  
Y Levy ◽  
S Labaume ◽  
MC Gendron ◽  
JC Brouet
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Plasma Cells ◽  
B Cell Differentiation ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Culture Supernatants

Abstract We previously showed that clonal blood B cells from patients with macroglobulinemia spontaneously differentiate in vitro to plasma cells. This process is dependent on an interleukin (IL)-6 autocrine pathway. We investigate here whether all-trans-retinoic acid (RA) interferes with B-cell differentiation either in patients with IgM gammapathy of undetermined significance (MGUS) or Waldenstrom's macroglobulinemia (WM). RA at a concentration of 10(-5) to 10(-8) mol/L inhibited by 50% to 80% the in vitro differentiation of purified B cells from four of five patients with MGUS and from one of five patients with WM as assessed by the IgM content of day 7 culture supernatants. We next determined whether this effect could be related to an inhibition of IL- 6 secretion by cultured B cells and/or a downregulation of the IL-6 receptor (IL-6R), which was constitutively expressed on patients' blood B cells. A 50% to 100% (mean, 80%) inhibition of IL-6 production was found in seven of 10 patients (five with MGUS and two with WM). The IL- 6R was no more detectable on cells from patients with MGUS after 2 days of treatment with RA and slightly downregulated in patients with WM. It was of interest that B cells susceptible to the action of RA belonged mostly to patients with IgM MGUS, which reinforces our previous data showing distinct requirements for IL-6-dependent differentiation of blood B cells from patients with VM or IgM MGUS.

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.

scholarly journals Simultaneous Determination of all-trans-Retinoic Acid, β-Carotene, and Vitamin A in Galenic Preparations by Liquid Chromatography

2001 ◽  
Vol 84 (2) ◽  
pp. 354-360
Author(s):  
Vincenzo Pucci ◽  
Francesca Bugamelli ◽  
Roberto Mandrioli ◽  
Maria A Raggi
Keyword(s):  
Liquid Chromatography ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Degradation Products ◽  
Extraction Procedure ◽  
Uv Detector ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Β Carotene

Abstract The concentrations of vitamin A, β-carotene, and all-trans-retinoic acid in oral preparations were determined in a single analysis by a method based on isocratic, reversed-phase liquid chromatography (LC). The LC system consisted of a C18 column, a mobile phase of acetonitrile, dichloromethane, methanol, and water and a UV detector set at 330 nm. The linearity ranges were 25–250 ng/mL for trans-retinoic acid and vitamin A, and 100–1000 ng/mL for β-carotene. This LC method for the determination of retinoids is simple, precise, and accurate. No extraction procedure is required before the chromatographic analysis; only a suitable dilution is necessary. The method proved to be reliable, fast, and economical. Furthermore, this method is indicative of stability, because it allows for the determination of degradation products such as 13-cis-retinoic acid.

scholarly journals All-trans-retinoyl β-glucuronide: new procedure for chemical synthesis and its metabolism in vitamin A-deficient rats

1996 ◽  
Vol 314 (1) ◽  
pp. 249-252 ◽  
Author(s):  
Bruno BECKER ◽  
Arun B. BARUA ◽  
James A. OLSON
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Chemical Synthesis ◽  
Glucuronic Acid ◽  
Major Metabolite ◽  
Triazole Derivative ◽  
Tetrabutylammonium Salt ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
High Yields

All-trans-retinoyl β-glucuronide (RAG) was chemically synthesized in high yields (up to 79%) by a new procedure involving the reaction of the tetrabutylammonium salt of glucuronic acid with all-trans-retinoic acid (RA) via the imidazole or triazole derivative. When RAG was fed orally to vitamin A-deficient rats, RA was identified as the major metabolite in the serum within hours of administration of RAG. Very little or no RAG was detected in the serum. Thus RAG, which was not appreciably hydrolysed to RA in vitamin A-sufficient rats [Barua and Olson (1987) Biochem J. 263, 403–409], was rapidly converted into RA in vitamin A-deficient rats.

Retinoic acid reverses the airway hyperresponsiveness but not the parenchymal defect that is associated with vitamin A deficiency

2004 ◽  
Vol 286 (2) ◽  
pp. L437-L444 ◽  
Author(s):  
Stephen E. McGowan ◽  
Amey Jo Holmes ◽  
Jennifer Smith
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Airway Hyperresponsiveness ◽  
Vitamin A Deficiency ◽  
Elastic Fibers ◽  
Bronchial Wall ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Airway Caliber ◽  
And Function

Airway hyperresponsiveness (AHR) is influenced by structural components of the bronchial wall, including the smooth muscle and connective tissue elements and the neuromuscular function. AHR is also influenced by parenchymally derived tethering forces on the bronchial wall, which maintain airway caliber by producing outward radial traction. Our previous work has shown that vitamin A-deficient (VAD) rats exhibit cholinergic hyperresponsiveness and a decrease in the expression and function of the muscarinic-2 receptors (M2R). We hypothesized that if decreases in radial traction from airway or parenchymal structures contributed to the VAD-related increase in AHR, then the radial traction would normalize more slowly than VAD-related alterations in neurotransmitter signaling. Rats remained vitamin A sufficient (VAS) or were rendered VAD and then maintained on the VAD diet in the presence or absence of supplementation with all- trans retinoic acid (RA). VAD was associated with an approximately twofold increase in respiratory resistance and elastance compared with VAS rats. Exposure to RA for 12 days but not 4 days restored resistance and elastance to control (VAS) levels. In VAD rats, AHR was accompanied by decreases in bronchial M2R gene expression and function, which were restored after 12 days of RA supplementation. Subepithelial bronchial elastic fibers were decreased by ∼50% in VAD rats and were significantly restored by RA. The increase in AHR that is associated with VAD is accompanied by decreases in M2R expression and function that can be restored by RA and a reduction in airway elastic fibers that can be partially restored by RA.

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