scholarly journals Retinoic Acid and Its Derivatives in Skin

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2660
Author(s):  
Łukasz Szymański ◽  
Rafał Skopek ◽  
Małgorzata Palusińska ◽  
Tino Schenk ◽  
Sven Stengel ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Therapeutic Potential ◽  
Multiple Organ ◽  
Retinoic Acid Receptors ◽  
All Trans Retinoic Acid ◽  
Organ Systems ◽  
Cell Growth And Differentiation ◽  
Dermatological Disorders ◽  
Dermal Cells

The retinoids are a group of compounds including vitamin A and its active metabolite all-trans-retinoic acid (ATRA). Retinoids regulate a variety of physiological functions in multiple organ systems, are essential for normal immune competence, and are involved in the regulation of cell growth and differentiation. Vitamin A derivatives have held promise in cancer treatment and ATRA is used in differentiation therapy of acute promyelocytic leukemia (APL). ATRA and other retinoids have also been successfully applied in a variety of dermatological conditions such as skin cancer, psoriasis, acne, and ichthyosis. Moreover, modulation of retinoic acid receptors and retinoid X (or rexinoid) receptors function may affect dermal cells. The studies using complex genetic models with various combinations of retinoic acid receptors (RARs) and retinoid X (or rexinoid) receptors (RXRs) indicate that retinoic acid and its derivatives have therapeutic potential for a variety of serious dermatological disorders including some malignant conditions. Here, we provide a synopsis of the main advances in understanding the role of ATRA and its receptors in dermatology.

Nuclear and extranuclear effects of vitamin A

2015 ◽  
Vol 93 (12) ◽  
pp. 1065-1075 ◽  
Author(s):  
Madina Iskakova ◽  
Mikhail Karbyshev ◽  
Aleksandr Piskunov ◽  
Cécile Rochette-Egly
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Nuclear Receptors ◽  
Target Genes ◽  
Dependent Manner ◽  
Active Metabolites ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Cell Growth And Differentiation ◽  
Per Se

Vitamin A or retinol is a multifunctional vitamin that is essential at all stages of life from embryogenesis to adulthood. Up to now, it has been accepted that the effects of vitamin A are exerted by active metabolites, the major ones being 11-cis retinal for vision, and all trans-retinoic acid (RA) for cell growth and differentiation. Basically RA binds nuclear receptors, RARs, which regulate the expression of a battery of target genes in a ligand dependent manner. During the last decade, new scenarios have been discovered, providing a rationale for the understanding of other long-noted but not explained functions of retinol. These novel scenarios involve: (i) other nuclear receptors such as PPAR β/δ, which regulate the expression of other target genes with other functions; (ii) extranuclear and nontranscriptional effects, such as the activation of kinases, which phosphorylate RARs and other transcription factors, thus expanding the list of the RA-activated genes; (iii) finally, vitamin A is active per se and can work as a cytokine that regulates gene transcription by activating STRA6. New effects of vitamin A and RA are continuously being discovered in new fields, revealing new targets and new mechanisms thus improving the understanding the pleiotropicity of their effects.

scholarly journals Restoration of Retinoid Sensitivity by MDR1 Ribozymes in Retinoic Acid–Resistant Myeloid Leukemic Cells

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2452-2458 ◽  
Author(s):  
Hiromichi Matsushita ◽  
Masahiro Kizaki ◽  
Hiroyuki Kobayashi ◽  
Hironori Ueno ◽  
Akihiro Muto ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cellular Proliferation ◽  
Therapeutic Potential ◽  
Acquired Resistance ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
P Glycoprotein ◽  
All Trans Retinoic Acid ◽  
Mdr1 Mrna

Complete remission is achieved in a high proportion of patients with acute promyelocytic leukemia (APL) after all-trans retinoic acid (RA) treatment, but most patients relapse and develop RA-resistant APL. We have previously reported that both RA-resistant HL-60 (HL-60R) and APL cells express P-glycoprotein and MDR1 transcripts; and these cells differentiate to mature granulocytes after culture with RA and P-glycoprotein antagonist. Ribozymes have been shown to be able to intercept a target RNA by catalytic activity. To address the role of MDR1 in overcoming RA-resistance in APL cells, we investigated the biologic effects of ribozymes against the MDR1 transcript in HL-60R cells. These ribozymes efficiently cleaved MDR1 mRNA at a specific site in vitro. The 196 MDR1 ribozyme was cloned into an expression vector, and stably transfected (HL-60R/196Rz) cells were obtained. Expression of MDR1 transcripts was decreased in HL-60R/196Rz cells compared with parental HL-60R and empty vector-transfected (HL-60R/neo) cells. Interestingly, RA inhibited cellular proliferation and induced differentiation of HL-60R/196Rz cells in a dose-dependent manner, suggesting reversal of drug resistance in HL-60R cells by the MDR1 ribozyme. These data are direct evidence that P-glycoprotein/MDR1 is responsible in part for acquired resistance to RA in myeloid leukemic cells. The MDR1 ribozyme may be a useful tool for investigating the biology of retinoid resistance and may have therapeutic potential for patients with RA-resistant APL.

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 Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo

Oncotarget ◽  
2016 ◽  
Vol 7 (29) ◽  
pp. 46028-46041 ◽  
Author(s):  
Farzaneh Atashrazm ◽  
Ray M. Lowenthal ◽  
Joanne L. Dickinson ◽  
Adele F. Holloway ◽  
Gregory M. Woods
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Therapeutic Potential ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

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.

Retinoid Therapy for Severe Dermatological Disorders

PEDIATRICS ◽  
1992 ◽  
Vol 90 (1) ◽  
pp. 119-120
Author(s):  
Keyword(s):  
Retinoic Acid ◽  
Severe Psoriasis ◽  
Childbearing Age ◽  
Systemic Corticosteroids ◽  
All Trans Retinoic Acid ◽  
Uva Light ◽  
Dermatological Disorders ◽  
Teratogenic Potential ◽  
Vitamin A Derivative ◽  
Systemic Antibiotics

Isotretinoin is approved for the treatment of severe recalcitrant cystic acne, and etretinate is approved for the treatment of severe recalcitrant psoriasis. Women of childbearing age place their infants at risk should these compounds be used during pregnancy and, in the case of etretinate, even before pregnancy. The purpose of this statement is to describe the indications for the use of these drugs and to advise physicians of their common side effects and their teratogenic potential. Isotretinoin, 13-cis-retinoic acid (Accutane, Hoffmann-LaRoche), is a vitamin A derivative that is effective in the treatment of severe cystic acne. This type of acne, affecting adolescents and young adults, is severe, nodular, cystic, and conglobate—a scarring disease that resists treatment with topical or systemic antibiotics, benzoyl peroxide, all-trans-retinoic acid, and intralesional corticosteroids. Adolescents with less severe forms of acne who learn about the therapeutic triumphs of isotretinoin in severe recalcitrant nodular and cystic acne may assume that the drug also would be beneficial for them. Physicians should explain to these adolescents why isotretinoin is not indicated in the treatment of typical acne. Another retinoid, etretinate (Tegison, Hoffmann-La Roche), is now available for the treatment of severe psoriasis that is unresponsive to standard therapies (topical tar with UVB light, anthralin, UVA light and psoralens, systemic corticosteroids and methotrexate). Etretinate is used for severe psoriasis of both the erythrodermic and generalized pustular types. Individualization of etretinate dosage is important. Most patients are started at a dosage of 0.75 to 1.0 mg/kg of body weight per day in divided doses.

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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