Isolation and identification of 5,6-epoxyretinoic acid: a biologically active metabolite of retinoic acid

Biochemistry ◽  
1978 ◽  
Vol 17 (19) ◽  
pp. 4085-4090 ◽  
Author(s):  
Anne M. McCormick ◽  
Joseph L. Napoli ◽  
Heinrich K. Schnoes ◽  
Hector F. DeLuca
Keyword(s):  
Retinoic Acid ◽  
Active Metabolite ◽  
Biologically Active ◽  
Isolation And Identification

scholarly journals Regulation of Hepatitis C Virus Infection by Cellular Retinoic Acid Binding Proteins through the Modulation of Lipid Droplet Abundance

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Bo-Ram Bang ◽  
Meng Li ◽  
Kuen-Nan Tsai ◽  
Haruyo Aoyagi ◽  
Shin-Ae Lee ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Life Cycle ◽  
Hepatitis C ◽  
Vitamin A ◽  
Active Metabolite ◽  
Antiviral Effect ◽  
Biologically Active ◽  
Viral Pathogens ◽  
Intrinsic Mechanism ◽  
Retinoic Acid Binding Proteins

ABSTRACTRetinoid (vitamin A) is an essential diet constituent that governs a broad range of biological processes. Its biologically active metabolite, all-transretinoic acid (ATRA), exhibits a potent antiviral property by enhancing both innate and adaptive antiviral immunity against a variety of viral pathogens, such as, but not limited to, HIV, respiratory syncytial virus (RSV), herpes simplex virus (HSV), and measles. Even though the hepatocyte is highly enriched with retinoid and its metabolite ATRA, it supports the establishment of efficient hepatitis C virus (HCV) replication. Here, we demonstrate the hepatocyte-specific cell-intrinsic mechanism by which ATRA exerts either a proviral or antiviral effect, depending on how it engages cellular retinoic acid binding proteins (CRABPs). We found that the engagement of CRABP1 by ATRA potently supported viral infection by promoting the accumulation of lipid droplets (LDs), which robustly enhanced the formation of a replication complex on the LD-associated endoplasmic reticulum (ER) membrane. In contrast, ATRA binding to CRABP2 potently inhibited HCV via suppression of LD accumulation. However, this antiviral effect of CRABP2 was abrogated due to the functional and quantitative predominance of CRABP1 in the hepatocytes. In summary, our study demonstrates that CRABPs serve as an on-off switch that modulates the efficiency of the HCV life cycle and elucidates how HCV evades the antiviral properties of ATRA via the exploitation of CRABP1 functionality.IMPORTANCEATRA, a biologically active metabolite of vitamin A, exerts pleiotropic biological effects, including the activation of both innate and adaptive immunity, thereby serving as a potent antimicrobial compound against numerous viral pathogens. Despite the enrichment of hepatocytes with vitamin A, HCV still establishes an efficient viral life cycle. Here, we discovered that the hepatocellular response to ATRA creates either a proviral or an antiviral environment depending on its engagement with CRABP1 or -2, respectively. CRABP1 supports the robust replication of HCV, while CRABP2 potently inhibits the efficiency of viral replication. Our biochemical, genetic, and microscopic analyses reveal that the pro- and antiviral effects of CRABPs are mediated by modulation of LD abundance, where HCV establishes the platform for viral replication and assembly on the LD-associated ER membrane. This study uncovered a cell-intrinsic mechanism by which HCV exploits the proviral function of CRABP1 to establish an efficient viral life cycle.

scholarly journals A biologically active metabolite of retinoic acid from rat liver

1965 ◽  
Vol 97 (1) ◽  
pp. 180-186 ◽  
Author(s):  
M Zile ◽  
HF Deluca
Keyword(s):  
Retinoic Acid ◽  
Methyl Ester ◽  
Vitamin A ◽  
Active Metabolite ◽  
Active Form ◽  
Active Material ◽  
Biologically Active ◽  
Growth Assay ◽  
Hydrolysis Of ◽  
Acidic Compound

1. Four major radioactive fractions have been isolated from the livers of vitamin A-deficient rats given [6,7-(14)C(2)]retinoic acid. 2. At least one of these was more potent than retinoic acid and approximately equal to retinol in the growth assay for vitamin A activity. 3. The biologically active material was chromatographically distinct from retinoic acid, retinol and retinal. 4. Alkaline hydrolysis of this material yielded an acidic compound containing all the radioactivity. 5. The methyl ester of the acidic product was unlike the methyl ester of retinoic acid in its chromatographic behaviour. 6. It is suggested that this metabolite may represent the active form of retinol in its growth-supporting role.

Spirodiketopiperazine-based CCR5 antagonists: Lead optimization from biologically active metabolite

2007 ◽  
Vol 17 (3) ◽  
pp. 727-731 ◽  
Author(s):  
Rena Nishizawa ◽  
Toshihiko Nishiyama ◽  
Katsuya Hisaichi ◽  
Naoki Matsunaga ◽  
Chiaki Minamoto ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Lead Optimization ◽  
Biologically Active ◽  
Ccr5 Antagonists

scholarly journals Anticapsin, a New Biologically Active Metabolite: Screening and Assay Procedures

1972 ◽  
Vol 24 (6) ◽  
pp. 907-910
Author(s):  
J. G. Whitney ◽  
Sandra S. Funderburk ◽  
J. E. Westhead ◽  
D. H. Lively ◽  
J. M. Solenberg ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Biologically Active ◽  
Metabolite Screening

scholarly journals THE STUDY OF THE DOMINANT GROUPS OF BIOLOGICALLY ACTIVE SUBSTANCES AND BIOELEMENTS IN SOME PLANTS OF THE FAMILY ROSACEAE

2017 ◽  
pp. 145-151
Author(s):  
Ефим (Efim) Авраамович (Avraamovich) Краснов (Krasnov) ◽  
Елена (Elena) Евгеньевна (Evgen'evna) Савельева (Savelyeva) ◽  
Надежда (Nadezhda) Кирилловна (Kirillovna) Рыжакова (Ryzhakova) ◽  
Ярослав (Yaroslav) Евгеньевич (Evgen'evich) Решетов (Reshetov) ◽  
Альбина (Al'bina) Равильевна (Ravil'evna) Гатауллина (Gataullina)
Keyword(s):  
Atomic Emission ◽  
Biologically Active Substances ◽  
Biologically Active ◽  
Isolation And Identification ◽  
Leading Role ◽  
Aerial Parts ◽  
Potentilla Anserina ◽  
Rosaceae Family ◽  
Innovative Drugs ◽  
Active Substances

To determine the content of the dominant groups of biologically active substances (tannins, polysaccharides, flavonoids) and bioelements in aerial parts of ten species of the Rosaceae family, which grows in Siberia: Potentilla anserina L., P. longifolia Willd., P. canescens Besser, P. bifurca L., P. tergemina Sojak, P. argentea L., P. goldbachii Rupr., P. sericea Dulac., Agrimonia pilosa Ledeb., Filipendula ulmaria (L.) Maxim. To determine the concentrations of essential and conditionally essential trace elements defined by the method of atomic emission spectroscopy. First identified plants of the genus Potentilla (P. canescens, P. tergemina) and Filipendula (F. ulmaria), accumulate significant quantities of lithium – 14,6, and 11,0 13,3 mg/kg, respectively, making them promising for further studies on the isolation and identification of active substances with the aim of creating innovative drugs. Investigated the content of heavy metals (Pb, Hg, As, Cd), the values of which meets regulatory requirements. Useful properties of the examined species family Rosaceae are determined by the content of biologically active substances (flavonoids, polysaccharides, tannins) and the complex of macro - and micronutrients. It is revealed that a dominant position in the spectrum belongs to the macronutrients potassium, calcium and magnesium (4,300 to 27,000 mg/kg). Among micronutrients the leading role is copper, followed by iron, silicon and manganese having important biological value, in particular, involved in the process of hematopoiesis.

scholarly journals Affinity purification of cellular retinoic acid-binding protein on 14-carboxy-13-cis-retinamide-sepharose 4B

1989 ◽  
Vol 262 (3) ◽  
pp. 917-922 ◽  
Author(s):  
R K Singh ◽  
B P Sani ◽  
M I Dawson ◽  
Y F Shealy
Keyword(s):  
Retinoic Acid ◽  
Carboxy Group ◽  
Binding Proteins ◽  
Binding Protein ◽  
Polyacrylamide Gel Electrophoresis ◽  
Biologically Active ◽  
Amide Bond ◽  
Gel Chromatography ◽  
Fatty Acid Binding ◽  
Sepharose 4B

A biologically active bifunctional retinoid, ethyl 14-carboxyretinoate, has been synthesized and shown to bind cellular retinoic acid (RA)-binding protein (CRABP) via its free carboxy group. We describe herein the synthesis of 14-carboxy-13-cis-retinamide-Sepharose 4B, which is an affinity matrix bearing an all-trans-RA moiety, and thus was used to purify and characterize CRABP from chick-embryo skin. An amide bond was first formed between the free carboxy group of the retinoid and a primary amino group of aminohexyl-Sepharose 4B, by reaction with carbodi-imide, and the ester group of the resin-bound retinoid was then hydrolysed in an alkaline medium. Polyacrylamide-gel electrophoresis and f.p.l.c. Superose column-chromatographic analysis demonstrated that the affinity-purified CRABP (Mr 15,000) was close to electrophoretic homogeneity (greater than 90%) and specifically interacts with RA. By using affinity gel chromatography, conversion of holo-CRABP into apo-CRABP by treatment with p-hydroxymercuribenzoate and a possible involvement of a thiol group in RA binding to CRABP were established. This affinity procedure provides several advantages: (i) 14-carboxy-13-cis-retinamide-Sepharose exhibited high efficiency and selectivity for RA-binding protein (i.e. retinol- or fatty-acid-binding proteins did not bind); (ii) the presence of the amide linkage between the ligand and the matrix makes this affinity resin relatively stable to cytosolic enzymes; and (iii) other RA-binding proteins, e.g. nuclear receptor(s), may be purified.

Control of beta-interferon expression in murine embryonal carcinoma F9 cells

1989 ◽  
Vol 9 (8) ◽  
pp. 3553-3556
Author(s):  
M K Francis ◽  
J M Lehman
Keyword(s):  
Retinoic Acid ◽  
Embryonal Carcinoma ◽  
Biologically Active ◽  
Rnase Protection ◽  
F9 Cells ◽  
Differentiated Cells ◽  
Transcriptional Regulatory Mechanism ◽  
Transcriptional Regulatory ◽  
Tissue Culture Model

Murine embryonal carcinoma F9 cells, a tissue culture model for early embryonic development, do not produce interferon (IFN) in response to poly(I-C), as determined by an antiviral assay. RNase protection analyses were used to examine total RNA extracted from the cells for the presence of beta-IFN RNA. Whereas F9 cells differentiated in vitro with retinoic acid produced a biologically active protein as well as beta-IFN RNA in response to poly(I-C), undifferentiated F9 cells produced no detectable beta-IFN RNA even in the presence of cycloheximide, an IFN-superinducing agent. These results show that undifferentiated embryonal carcinoma cells do not accumulate beta-IFN RNA in response to an IFN-inducing agent, suggesting a transcriptional regulatory mechanism. However, this control mechanism is altered upon differentiation, since the gene can be transcriptionally activated in retinoic acid-differentiated cells.

Noribogaine (12-Hydroxyibogamine): A Biologically Active Metabolite of the Antiaddictive Drug Ibogaine

2000 ◽  
Vol 914 (1) ◽  
pp. 354-368 ◽  
Author(s):  
M. H. BAUMANN ◽  
J. P. PABLO ◽  
S. F. ALI ◽  
R. B. ROTHMAN ◽  
D. C. MASH
Keyword(s):  
Active Metabolite ◽  
Biologically Active
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