scholarly journals All-trans retinoic acid reduces the transcriptional regulation of intestinal sodium-dependent phosphate co-transporter gene (Npt2b)

2020 ◽  
Vol 477 (4) ◽  
pp. 817-831 ◽  
Author(s):  
Masashi Masuda ◽  
Hironori Yamamoto ◽  
Yuichiro Takei ◽  
Otoki Nakahashi ◽  
Yuichiro Adachi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Retinoic Acid Receptor ◽  
Gene Promoter ◽  
Nih3t3 Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Sodium Dependent

Inorganic phosphate (Pi) homeostasis is regulated by intestinal absorption via type II sodium-dependent co-transporter (Npt2b) and by renal reabsorption via Npt2a and Npt2c. Although we previously reported that vitamin A-deficient (VAD) rats had increased urine Pi excretion through the decreased renal expression of Npt2a and Npt2c, the effect of vitamin A on the intestinal Npt2b expression remains unclear. In this study, we investigated the effects of treatment with all-trans retinoic acid (ATRA), a metabolite of vitamin A, on the Pi absorption and the Npt2b expression in the intestine of VAD rats, as well as and the underlying molecular mechanisms. In VAD rats, the intestinal Pi uptake activity and the expression of Npt2b were increased, but were reduced by the administration of ATRA. The transcriptional activity of reporter plasmid containing the promoter region of the rat Npt2b gene was reduced by ATRA in NIH3T3 cells overexpressing retinoic acid receptor (RAR) and retinoid X receptor (RXR). On the other hand, CCAAT/enhancer-binding proteins (C/EBP) induced transcriptional activity of the Npt2b gene. Knockdown of the C/EBP gene and a mutation analysis of the C/EBP responsible element in the Npt2b gene promoter indicated that C/EBP plays a pivotal role in the regulation of Npt2b gene transcriptional activity by ATRA. EMSA revealed that the RAR/RXR complex inhibits binding of C/EBP to Npt2b gene promoter. Together, these results suggest that ATRA may reduce the intestinal Pi uptake by preventing C/EBP activation of the intestinal Npt2b gene.

Regulation of renal sodium-dependent phosphate co-transporter genes (Npt2a and Npt2c) by all-trans-retinoic acid and its receptors

2010 ◽  
Vol 429 (3) ◽  
pp. 583-592 ◽  
Author(s):  
Masashi Masuda ◽  
Hironori Yamamoto ◽  
Mina Kozai ◽  
Sarasa Tanaka ◽  
Mariko Ishiguro ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Sodium Dependent ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular

The type II sodium-dependent phosphate co-transporters Npt2a and Npt2c play critical roles in the reabsorption of Pi by renal proximal tubular cells. The vitamin A metabolite ATRA (all-trans-retinoic acid) is important for development, cell proliferation and differentiation, and bone formation. It has been reported that ATRA increases the rate of Pi transport in renal proximal tubular cells. However, the molecular mechanism is still unknown. In the present study, we observed the effects of a VAD (vitamin A-deficient) diet on Pi homoeostasis and the expression of Npt2a and Npt2c genes in rat kidney. There was no change in the plasma levels of Pi, but VAD rats significantly increased renal Pi excretion. Renal brush-border membrane Pi uptake activity and renal Npt2a and Npt2c expressions were significantly decreased in VAD rats. The transcriptional activity of a luciferase reporter plasmid containing the promoter region of human Npt2a and Npt2c genes was increased markedly by ATRA and a RAR (retinoic acid receptor)-specific analogue TTNPB {4-[E-2-(5,6,7,8-tetrahydro-5,5,8,8-tetra-methyl-2-naphtalenyl)-1-propenyl] benzoic acid} in renal proximal tubular cells overexpressing RARs and RXRs (retinoid X receptors). Furthermore, we identified RAREs (retinoic acid-response elements) in both gene promoters. Interestingly, the half-site sequences (5′-GGTTCA-3′: −563 to −558) of 2c-RARE1 overlapped the vitamin D-responsive element in the human Npt2c gene and were functionally important motifs for transcriptional regulation of human Npt2c by ATRA and 1,25(OH)2D3 (1α,25-dihydroxyvitamin D3), in both independent or additive actions. In summary, we conclude that VAD induces hyperphosphaturia through the down-regulation of Npt2a and Npt2c gene expression in the kidney.

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 PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1313 ◽  
Author(s):  
Marta Sobas ◽  
Maria Carme Talarn-Forcadell ◽  
David Martínez-Cuadrón ◽  
Lourdes Escoda ◽  
María J. García-Pérez ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Complete Remission ◽  
Acute Promyelocytic Leukemia ◽  
Fusion Gene ◽  
Retinoic Acid Receptor ◽  
Promyelocytic Leukemia ◽  
High Relapse Rate ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Shed Light

It has been suggested that 1–2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RARα being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RARα and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RARα and 2 NPM1-RARα), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 × 109/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far.

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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