anhydrovitamin-a has been researched along with 14-hydroxy-4-14-retro-retinol* in 4 studies
4 other study(ies) available for anhydrovitamin-a and 14-hydroxy-4-14-retro-retinol
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Teratogenicity, tissue distribution, and metabolism of the retro-retinoids, 14-hydroxy-4,14-retro-retinol and anhydroretinol, in the C57BL/6J mouse.
The retro-retinoids 14-hydroxy-4,14-retro-retinol (14-HRR) and anhydroretinol (AR) are endogenous metabolites of retinol (Vitamin A). 14-HRR and retinol, but not retinoic acid, promote the proliferation of lymphocytes and fibroblasts when cultured in serum-free medium, whereas AR competitively inhibits these growth-supportive effects. Retinol and all-trans-retinoic acid are potent teratogens. This study shows the teratogenic potencies of 14-HRR and AR compared to retinol at a single gestational time. Also reported is the metabolism of these retinoids in nonpregnant mouse liver, the primary storage tissue of vitamin A, where many retinoids will be present at their highest concentration. Additionally, measurement of these metabolite concentrations was carried out in pregnant mouse plasma and embryos because they are the most relevant to teratology. Single intraperitoneal administration of 60 mg/kg of all-trans-retinol (retinol) to C57BL/6J mice at gestational day 7.5 produced a significant induction of eye and axial skeletal malformations. The equivalent dose of 14-HRR or AR induced a lower frequency of embryolethality and eye and axial skeletal malformations indicating that these retro-retinoids are less potent teratogens than retinol. The distribution of 14-HRR, AR, retinol, and their metabolites was determined in the liver at a single time point after retinoid administration. Two hours after 60 mg/kg of 14-HRR treatment, HRR esters are detected. Two hours after 600 mg/kg of AR treatment, 14-HRR is detected, suggesting that 14-HRR, a reported metabolite of retinol, can be biosynthesized from AR. In both cases, neither retinoic acid nor retro-retinoid acidic metabolites were detected. Two hours after 60 mg/kg of retinol treatment, 14-HRR, 13,14-dihydroxyretinol (DHR), AR, and retinoic acid were detected. A new endogenous retro-retinoid, to which the 4-hydro-5-hydroxy-anhydroretinol structure is proposed, was detected in all liver extracts. Retinoic acid, 14-HRR, and DHR were present in plasma and embryos of retinol-treated pregnant mice. Plasma and embryos of AR-treated pregnant mice contained 14-HRR and AR, but the retinoic acid concentration did not increase compared to controls. In summary, the retro-retinoids 14-HRR and AR are weaker teratogens than retinol. The low teratogenicity observed might be due to the facts that 14-HRR and AR do not contain the terminal carboxylic group involved in binding and activation of the retinoic acid nuclear receptors a Topics: Abnormalities, Drug-Induced; Animals; Binding, Competitive; Diterpenes; Dose-Response Relationship, Drug; Eye Abnormalities; Female; Injections, Intraperitoneal; Liver; Male; Mice; Mice, Inbred C57BL; Pregnancy; Tissue Distribution; Vitamin A | 2000 |
F-actin as a functional target for retro-retinoids: a potential role in anhydroretinol-triggered cell death.
The retro-retinoids, metabolites of vitamin A (retinol), belong to a family of lipophilic signalling molecules implicated in regulation of cell growth and survival. Growth-promoting properties have been ascribed to 14-hydroxy-retro-retinol (14HRR), while anhydroretinol (AR) was discovered to act as a natural antagonist triggering growth arrest and death by apoptosis. Based on morphological studies and inhibition of apoptosis by the kinase blocker, herbimycin A, it has been suggested that retro-retinoids exhibit their function in the cytosolic compartment. F-actin emerged as a functional target for retro-retinoid action. By FACS analysis and fluorescence microscopy of phalloidin-FITC labeled cells we demonstrated that F-actin reorganization was an early event in AR-triggered apoptosis. Fluorescence images of AR-treated fibroblasts displayed short, thick, stick-like and punctate structures, and membrane ruffles at the cell periphery along with an increased diffuse staining pattern. Reversal of the AR effect by 14HRR or retinol indicates that F-actin is a common site for regulation by retro-retinoids. Inhibition of both cell death and actin depolymerisation by bcl-2 implies that cytoskeleton reorganization is downstream of bcl-2-related processes. Furthermore, stabilization of microfilaments by jasplakinolide increased the survival potential of AR treated cells, while weakening the cytoskeleton by cytochalasin B abetted apoptosis. Thus the cytoskeleton is an important way station in a communication network that decides whether a cell should live or die. Topics: 3T3 Cells; Actins; Animals; Antineoplastic Agents; Apoptosis; Benzoquinones; Cell Survival; Cytochalasin B; Cytosol; Depsipeptides; Diterpenes; DNA Damage; Fibroblasts; Flow Cytometry; Kinetics; Lactams, Macrocyclic; Lymphoma; Mice; Peptides, Cyclic; Quinones; Retinoids; Rifabutin; Tumor Cells, Cultured; Vitamin A | 1999 |
Retro-retinoids in regulated cell growth and death.
Vitamin A serves as a prohormone from which three classes of active metabolites are derived: the aldehydes, the carboxylic acids, and the retro-retinoids. Although these three classes are united under the rubric of signal transduction, they act by different molecular mechanisms: the 11-cis-retinaldehydes combine with opsin to form the universal visual pigments and the retinoic acids form ligands for transcription factors, whereas the retro-retinoids, as shown here, intersect with signal transduction at a cytoplasmic or membrane site. The retro-retinoid, anhydroretinol (AR), has long been known to act as a growth inhibitor in lymphocytes, whereas 14-hydroxy-4,14-retro-retinol (14-HRR) is required for normal lymphocyte proliferation. A mutually reversible relationship exists between these two retro-retinoids as one can reverse the effects of the other when given in pharmacological doses. The common explanation for reversible inhibition is competition for a shared receptor. We now provide evidence that when AR is given to T cells unmitigated by 14-HRR, rapid cell death can occur. The circumstances are closely related to nonclassical forms of apoptosis: within 2 h of AR administration the T cells undergo widespread morphological changes, notably surface blebbing and ballooning and, inevitably, bursting. In contrast, nuclear changes are comparatively mild, as indicated by absence of chromatin condensation and overt DNA cleavage to discrete nucleosomal fragments, although DNA nicks are readily discernible by terminal deoxynucleotidyl transferase assay. What further distinguishes the AR-induced form of apoptosis from classical ones is a lack of requirements of messenger RNA and protein synthesis, suggesting that the events leading to cell death are primarily initiated and play themselves out in the cytoplasm. This view is further reinforced by the finding that herbimycin A can prevent the onset of programmed cell death. The importance of our findings is that they strongly suggest a second messenger role for vitamin A metabolites in the cytoplasmic realm that has not been seen previously. These findings are entirely compatible with a general notion that in a cell requiring multiple coordinated signals for survival, the provision of an unbalanced signal can initiate programmed cell death. Collectively, our data also challenge the paradigm that retinoids (outside vision) solely mediate their function via the steroid/ retinoic acid receptor family of nuclear transcr Topics: Animals; Cell Death; Cell Division; Cells, Cultured; Cytotoxicity, Immunologic; Diterpenes; DNA Damage; Humans; Mice; Retinoids; T-Lymphocytes; Vitamin A | 1996 |
Growth control or terminal differentiation: endogenous production and differential activities of vitamin A metabolites in HL-60 cells.
Vitamin A (retinol) is a prohormone that exerts its pleiotropic biological effects after conversion into multiple metabolites. In this report we describe the identification of three endogenous, retinolderived effector molecules, 14-hydroxy-retro-retinol (14-HRR), anhydroretinol (AR), and retinoic acid (RA) and a putative storage form of retinol, retinylesters (RE) in the human promyelocytic leukemia cell line HL-60. Exogenous application of the retinol metabolites in retinol-depleted serum-free cultures of HL-60 allowed the identification of unique cellular functions for each metabolite: 14-HRR is a growth factor for HL-60. AR is a functional antagonist of 14-HRR with growth-inhibiting activity, and RA is a potent inducer of granulocyte differentiation accompanied by growth arrest. Finally, intracellular RE serves as storage form allowing continuous production of 14-HRR when no external retinol is available. Topics: Cell Differentiation; Cell Division; Diterpenes; Granulocytes; Growth Inhibitors; Humans; In Vitro Techniques; Retinoids; Tretinoin; Tumor Cells, Cultured; Vitamin A | 1993 |