retinaldehyde and retinol-palmitate

A wide range of cosmeceutical products are available on the market currently, but evidence to support their use is often lacking in the literature. Specifically, there is a substantial amount of evidence supporting the efficacy of tretinoin in photoaging, but the evidence supporting retinoid-based cosmeceuticals remains sparse. The authors review the current data in the literature related to vitamin A-derived cosmeceutical products and conclude that cosmeceuticals containing retinaldehyde have been shown in large randomized, controlled trials to have the most beneficial effect on aging skin.

Topics: Administration, Topical; Antioxidants; Cosmetics; Dermatologic Agents; Diterpenes; Humans; Keratolytic Agents; Randomized Controlled Trials as Topic; Retinaldehyde; Retinoids; Retinyl Esters; Skin Aging; Tretinoin; Vitamin A

In this article, we survey recent advances in basic as well as clinical studies on retinoids including structure-function correlation of retinoids, effects of retinoids on cell growth, anticancer activities, immunological potentiation, initiation and promotion of cancer, differentiation, and chemoprevention.

Topics: Animals; Antibody Formation; Cell Differentiation; Cell Division; Diterpenes; Female; Humans; Male; Mice; Neoplasms; Retinaldehyde; Retinyl Esters; Vitamin A

Although retinoids have been reported to be present and active in vertebrates and invertebrates, the presence of mechanisms for retinoid storage in the form of retinyl esters, a key feature to maintain whole-organism retinoid homeostasis, have been considered to date a vertebrate innovation. Here we demonstrate for the first time the presence of retinol and retinyl esters in an invertebrate lophotrochozoan species, the gastropod mollusk Osilinus lineatus. Furthermore, through a pharmacological approach consisting of intramuscular injections of different retinoid precursors, we also demonstrate that the retinol esterification pathway is active in vivo in this species. Interestingly, retinol and retinyl esters were only detected in males, suggesting a gender-specific role for these compounds in the testis. Females, although lacking detectable levels of retinol or retinyl esters, also have the biochemical capacity to esterify retinol, but at a lower rate than males. The occurrence of retinyl ester storage capacity, together with the presence in males and females of active retinoids, i.e., retinoic acid isomers, indicates that O. lineatus has a well developed retinoid system. Hence, the present data strongly suggest that the capacity to maintain retinoid homeostasis has arisen earlier in Bilateria evolution than previously thought.

Topics: Animals; Biological Evolution; Chromatography, High Pressure Liquid; Diterpenes; Esterification; Female; Homeostasis; Male; Microinjections; Mollusca; Muscles; Retinaldehyde; Retinyl Esters; Testis; Tretinoin; Vitamin A

Rhodopsin activation is measured by the early receptor current (ERC), a conformation-associated charge motion, in human embryonic kidney cells (HEK293S) expressing opsins. After rhodopsin bleaching in cells loaded with 11-cis-retinal, ERC signals recover in minutes and recurrently over a period of hours by simple dark adaptation, with no added chromophore. The purpose of this study is to investigate the source of ERC signal recovery in these cells. Giant HEK293S cells expressing normal wild-type (WT)-human rod opsin (HEK293S) were regenerated by solubilized 11-cis-retinal, all-trans-retinal, or Vitamin A in darkness. ERCs were elicited by flash photolysis and measured by whole-cell recording. Visible flashes initially elicit bimodal (R(1), R(2)) ERC signals in WT-HEK293S cells loaded with 11-cis-retinal for 40 min or overnight. In contrast, cells regenerated for 40 min with all-trans-retinal or Vitamin A had negative ERCs (R(1)-like) or none at all. After these were placed in the dark overnight, ERCs with outward R(2) signals were recorded the following day. This indicates conversion of loaded Vitamin A or all-trans-retinal into cis-retinaldehyde that regenerated ground-state pigment. 4-butylaniline, an inhibitor of the mammalian retinoid cycle, reversibly suppressed recovery of the outward R(2) component from Vitamin A and 11-cis-retinal-loaded cells. These physiological findings are evidence for the presence of intrinsic retinoid processing machinery in WT-HEK293S cells similar to what occurs in the mammalian eye.

Topics: Aniline Compounds; Cell Line; Dark Adaptation; Diterpenes; Humans; Kidney; Photic Stimulation; Retinaldehyde; Retinyl Esters; Rhodopsin; Vision, Ocular; Vitamin A

In the retinal rod and cone photoreceptors, light photoactivates rhodopsin or cone visual pigments by converting 11-cis-retinal to all-trans-retinal, the process that ultimately results in phototransduction and visual sensation. The production of 11-cis-retinal in adjacent retinal pigment epithelial (RPE) cells is a fundamental process that allows regeneration of the vertebrate visual system. Here, we present evidence that all-trans-retinol is unstable in the presence of H(+) and rearranges to anhydroretinol through a carbocation intermediate, which can be trapped by alcohols to form retro-retinyl ethers. This ability of all-trans-retinol to form a carbocation could be relevant for isomerization. The calculated activation energy of isomerization of all-trans-retinyl carbocation to the 11-cis-isomer was only approximately 18 kcal/mol, as compared to approximately 36 kcal/mol for all-trans-retinol. This activation energy is similar to approximately 17 kcal/mol obtained experimentally for the isomerization reaction in RPE microsomes. Mass spectrometric (MS) analysis of isotopically labeled retinoids showed that isomerization proceeds via alkyl cleavage mechanism, but the product of isomerization depended on the specificity of the retinoid-binding protein(s) as evidenced by the production of 13-cis-retinol in the presence of cellular retinoid-binding protein (CRBP). To test the influence of an electron-withdrawing group on the polyene chain, which would inhibit carbocation formation, 11-fluoro-all-trans-retinol was used in the isomerization assay and was shown to be inactive. Together, these results strengthen the idea that the isomerization reaction is driven by mass action and may occur via carbocation intermediate.

Topics: Animals; Cattle; cis-trans-Isomerases; Diterpenes; Humans; Hydrochloric Acid; Isomerism; Mass Spectrometry; Mathematical Computing; Microsomes; Photochemistry; Pigment Epithelium of Eye; Retinaldehyde; Retinoids; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Retinyl Esters; Sodium Hydroxide; Vitamin A

The binding of the lipophilic nutrients, retinal, vitamin D2, and retinyl palmitate by beta-lactoglobulin was measured by analysis of changes in the fluorescence of the tryptophanyl residue of beta-lactoglobulin or the retinyl moiety. The fluorescence intensity of the tryptophanyl residue was quenched by retinoid or vitamin D binding but was enhanced by palmitate binding. The analysis of competitive binding experiments with palmitate indicated that retinal and palmitate did not compete for the same site; however, vitamin D2, which binds with a stoichiometry of 2, appeared to displace palmitate at higher concentrations. Also, the retinoids and vitamin D2 were bound more tightly than was palmitate. The results are consistent with the model in which the retinoids and vitamin D2 bind in the calyx formed by the beta-barrel; palmitate and a second molecule of vitamin D2 bind in a surface pocket near the dimer contact region. Retinyl palmitate, which has both moieties, appeared to bind at both sites.

Topics: Adsorption; Binding, Competitive; Diterpenes; Ergocalciferols; Hydrogen-Ion Concentration; Lactoglobulins; Retinaldehyde; Retinyl Esters; Spectrometry, Fluorescence; Tryptophan; Vitamin A

A therapeutic effect of vitamin A supplementation on the course of photoreceptor degeneration, previously reported for patients with retinitis pigmentosa, was tested in two transgenic mouse models of this disease, each carrying a dominant rhodopsin mutation. The threonine-17 --> methionine (T17M) mutation is a class II rhodopsin mutation, characterized by a thermal instability/folding defect and minimal regeneration with the chromophore. The proline-347 --> serine (P347S) mutation belongs to class I, comprised of a smaller number of mutations that exhibit no recognized biochemical abnormality in vitro. In the present study, each of the two mouse models was fed a diet containing 2.5 mg of vitamin A palmitate (control) or 102.5 mg of vitamin A palmitate (high vitamin A) per kilogram of diet. Dark-adapted, full-field electroretinograms showed that the high vitamin A diet significantly reduced the rate of decline of a-wave and b-wave amplitudes in the T17M mice but had no significant effect on the decline of electroretinogram amplitude in the P347S mice. Correspondingly, histologic evaluation revealed that the treatment was associated with significantly longer photoreceptor inner and outer segments and a thicker outer nuclear layer in the T17M mice but had no effect on photoreceptor morphology in the P347S mice. In a separate series of experiments, the instability defect of the T17M mutant opsin expressed in vitro was partially alleviated by inclusion of 11-cis-retinal in the culture media. These results show that vitamin A supplementation slows the rate of photoreceptor degeneration caused by a class II rhodopsin mutation. Vitamin A supplementation may confer therapeutic benefit by stabilizing mutant opsins through increased availability of the chromophore.

Topics: Animals; Cells, Cultured; Diterpenes; Electroretinography; Gene Expression; Humans; Liver; Mice; Mice, Transgenic; Microscopy, Electron; Photoreceptor Cells; Point Mutation; Retina; Retinaldehyde; Retinitis Pigmentosa; Retinyl Esters; Rhodopsin; Transfection; Vitamin A

The retina and retinal pigment epithelium contain a number of retinoids in a metabolic pathway that eventually forms the visual pigments. This study investigates the photochemistry of those retinoids that may contribute to light-induced damage to the retina. These include retinal (RAL), retinol (ROL), retinylpalmitate (ROLpal) and the protonated Schiff-base of retinal (RALsb). Their photochemistry was followed by both EPR spin-trapping techniques and the direct detection of singlet oxygen via its luminescence at 1270 nm. Irradiation (> 300 nm) of RAL, ROL in methanol (MeOH) or RALpal in dimethylformamide, produces free radicals from both solvents. Illumination of RALsb in MeOH containing NADH with light above 400 nm (and even above 455 nm) generates the superoxide radical. We also determined that the quantum yields for singlet oxygen sensitization by RAL, ROL or RALpal in MeOH are 0.05, 0.03 and < 0.01, respectively. These values are at least 75% less than those previously found using chemical methods. These observations indicate that a major photochemical process for these retinoids may be an electron (or hydrogen) process that will lead to radical products, and that the singlet oxygen mechanism is of relatively minor importance in protic solvents. These results may explain the action spectra obtained from light-induced damage to the retina.

Topics: Diterpenes; Electron Spin Resonance Spectroscopy; Free Radicals; Humans; Kinetics; Light; Photochemistry; Retina; Retinaldehyde; Retinoids; Retinyl Esters; Schiff Bases; Vitamin A

Biological functions of retinoids in the vertebrate retina include the role of 11-cis retinaldehyde as visual pigment chromophore, and possible effects of retinoic acid in histogenesis and cell survival. Qualitative and quantitative regulation of retinoid availability for these complex processes could involve several cell types, including retinal pigment epithelium, Müller glia and retinal photoreceptors and non-photoreceptor neurons; their relative contributions, however, have not been fully elucidated. Using purified cultures, we have carried out a study of cell-type-specific metabolism and storage of retinoids in chick embryo retinal photoreceptors and other neuronal cells, as compared to those of retinal glia. Retinal glia were found to synthesize both retinoic acid and retinyl esters, and to hydrolyse the latter; they also displayed retinol dehydrogenase activities. Cultured neurons and photoreceptors also synthesized and hydrolysed retinyl esters; their capacity for retinaldehyde synthesis from a retinol or retinyl ester substrate suggested the presence of retinol dehydrogenase activity. Retinoic acid was not synthesized in differentiated neuronal cultures, although some synthesis was detectable at early culture stages when the cells were still morphologically undifferentiated. These findings indicate that cell-type-specific metabolic activities are expressed during retinal cell differentiation in vitro, and that embryonic retinal photoreceptors and nonphotoreceptor neurons are active participants in the metabolism and storage of retinoids.

Topics: Animals; Cells, Cultured; Chick Embryo; Diterpenes; Neuroglia; Neurons; Photoreceptor Cells; Retina; Retinaldehyde; Retinoids; Retinyl Esters; Tretinoin; Vitamin A

The amounts of endogenous retinyl palmitate, retinol and retinaldehyde were measured in the neural retina and retinal pigment epithelium (RPE) of predominantly cone (chicken), rod (rat) and more mixed (cat, human) retinae. The ratio of 11-cis to all-trans isomers of retinyl palmitate and retinol in the neural retina and the RPE increases progressively with the increase in diurnality of the species from rat to chicken. The membrane fractions of both chicken and bovine RPE enzymically isomerize all-trans retinol to 11-cis-retinol. Chicken neural retina membranes enzymically form 11-cis-retinol and all-trans-retinyl palmitate from all-trans-retinol. Light and electron microscopy revealed no contamination of chicken neural retina by RPE. Muller cells from chicken retina were isolated, cultured and characterized by immunocytochemical localization of cellular retinaldehyde-binding protein. Cultured chicken Muller cells form all-trans-retinyl palmitate, 11-cis-retinol and 11-cis-retinyl palmitate from all-trans-retinol and release most of the 11-cis-retinol into the medium. The results indicate that chicken neural retina and Muller cells in particular synthesize 11-cis-retinoids from all-trans-retinol.

Topics: Animals; Cats; Cattle; Cell Membrane; Cells, Cultured; Chickens; Diterpenes; Humans; Immunohistochemistry; Isomerism; Microscopy, Electron; Photoreceptor Cells; Pigment Epithelium of Eye; Retina; Retinaldehyde; Retinyl Esters; Vitamin A

The changes of egg retinoids during the development of Xenopus laevis were investigated by high-performance liquid chromatography (HPLC). All-trans retinal and 3-dehydroretinal are endogenous in the egg and are distributed to both the eyes and the ventral portion of the larval body. These retinals are converted to all-trans retinyl palmitate and 3-dehydroretinyl palmitate during the development up to stage 46. 11-cis retinal and 3-dehydroretinal can be detected after stage 40 in the eyes but not in the larval ventral portion. It is suggested that retinoids are transported from the larval ventral portion to the eyes after stage 41/42.

Topics: Animals; Chromatography, High Pressure Liquid; Diterpenes; Eye; Larva; Ovum; Retina; Retinaldehyde; Retinoids; Retinyl Esters; Time Factors; Vitamin A; Xenopus laevis

Upon absorption of a photon, the 11-cis retinaldehyde chromophore of rhodopsin is isomerized and reduced to all-trans retinol (vitamin A) in the photoreceptor outer segments, whereupon it leaves the photoreceptors, and moves to the retinal pigment epithelium (RPE). To clarify the function of the RPE in the regeneration of 11-cis retinaldehyde, we delivered all-trans retinol to monolayer cultures of human RPE. During delivery the retinol was associated with its putative natural carrier, interphotoreceptor retinoid binding protein (IRBP). IRBP has been proposed as a carrier protein involved in the exchange of retinoids between the photoreceptors and the retinal pigment epithelium. The retinoid composition of RPE cells and culture medium was analyzed by HPLC following several incubation periods. The RPE monolayer was found to process all-trans retinol into two distinct end-products: all-trans retinyl palmitate, which remained within the RPE monolayer: and 11-cis retinaldehyde which was released into the culture medium. These results demonstrate retinoid isomerase, retinol oxidoreductase and retinyl ester synthetase activity in human RPE cells cultured under the appropriate conditions. They show that IRBP can serve as a carrier of retinol through an aqueous medium to the RPE, and they illustrate that the visual cycle can be studied in vitro.

Topics: Cells, Cultured; Chromatography, High Pressure Liquid; Diterpenes; Eye Proteins; Humans; Pigment Epithelium of Eye; Retinaldehyde; Retinoids; Retinol-Binding Proteins; Retinyl Esters; Time Factors; Vitamin A

The synthesis and release of 11-cis-retinoids by primary cultures of human retinal pigment epithelium (RPE) and the transfer of these retinoids to co-incubated human rod outer segments (ROS) were studied. Monolayers of 2-3-week-old cultured RPE incorporate tritiated all-trans-retinol, esterify it to the corresponding retinyl palmitate, form 11-cis-retinol and 11-cis-retinaldehyde and release retinaldehyde into the culture medium. The ratio of 11-cis to all-trans isomers of retinol, retinyl palmitate and retinaldehyde formed in the cells along with retinaldehyde released and incorporated into the ROS progressively increases, indicating a progressive increase in the concentration of 11-cis isomer from the time it is formed in RPE cells until its transfer to ROS. Incorporation of 11-cis-retinaldehyde into the ROS is directly related to the amount of albumin present in the media, suggesting the transfer of retinoids from RPE to photoreceptor to be a protein-mediated process. Events leading to isomerization, esterification, oxidation and release of retinoids by human RPE and incorporation of retinoids into ROS can therefore be examined in vitro.

Topics: Adult; Aged; Biological Transport; Cells, Cultured; Chromatography, High Pressure Liquid; Diterpenes; Esterification; Humans; Kinetics; Middle Aged; Oxidation-Reduction; Photoreceptor Cells; Pigment Epithelium of Eye; Retinaldehyde; Retinoids; Retinyl Esters; Rod Cell Outer Segment; Stereoisomerism; Vitamin A

Drugs which affect the processing of vitamin A in the retina or pigment epithelium can cause ocular toxicity. It is shown here that the retinoic acids, which are used in the treatment of skin disorders and which cause night blindness, inhibit the ocular retinol dehydrogenases in an in vitro system. This is shown to lead to a decrease in the formation of the visual chromophore 11-cis-retinal, thus explaining why night blindness might occur.

Topics: Alcohol Oxidoreductases; Animals; Diterpenes; Night Blindness; Pigment Epithelium of Eye; Rana pipiens; Retina; Retinaldehyde; Retinyl Esters; Tretinoin; Vitamin A

Vitamin A (retinol) and some of its analogs exhibited varying degrees of inhibition on induced iron and ascorbic acid lipid peroxidation of rat brain mitochondria. Malonyldialdehyde production was used as an index of the extent of in vitro lipid peroxidation. The fat-soluble vitamins retinol, retinol acetate, retinoic acid, retinol palmitate, and retinal at concentrations between 0.1 and 10.0 mmol/L inhibited brain lipid peroxidation. Retinol and retinol acetate were the most effective inhibitors. It is concluded from this study that retinol and its analogs can be considered as potential antioxidant factors, more potent than some of the well-known antioxidants such as alpha-tocopherol and butylated hydroxytoluene.

Topics: Animals; Ascorbic Acid; Brain; Diterpenes; Ferrous Compounds; Free Radicals; Lipid Peroxidation; Male; Malondialdehyde; Mitochondria; Rats; Rats, Inbred Strains; Retinaldehyde; Retinyl Esters; Tretinoin; Vitamin A

Retinoids in the eyes of Xenopus laevis at several developmental stages, were analyzed by high-performance liquid chromatography (HPLC). At stage 37/38, larval eyes contained mainly all-trans isomers of retinal, 3-dehydroretinal, retinyl ester and 3-dehydroretinyl ester. Ratios of all-trans 3-dehydroretinal to retinal and of all-trans 3-dehydroretinyl ester to retinyl ester were almost 1 at the stage. With the advance of development, the amounts of all-trans retinal and 3-dehydroretinal decreased; however, those of all-trans retinyl ester and 3-dehydroretinyl ester increased. The chromophores of visual pigments, 11-cis retinal and 3-dehydroretinal, were detected at stage 40 (total; 0.2 pmol/eye) and their amounts increased after that stage. The ratio of 11-cis 3-dehydroretinal to retinal was almost 1 at stages 40-42. The ratio became larger after stage 43 and was almost 19 at stage 46. The ratio of all-trans 3-dehydroretinyl ester to retinyl ester, also, increased after stage 42 and reached 11 at stage 46. The mechanism of 11-cis formation during development is discussed in relation to retinoid conversions in the eyes.

Topics: Animals; Chromatography, High Pressure Liquid; Diterpenes; Embryo, Nonmammalian; Retina; Retinal Pigments; Retinaldehyde; Retinoids; Retinyl Esters; Vitamin A; Xenopus laevis

Previously, we have shown that retina/pigment epithelium membranes from the amphibian can synthesize 11-cis-retinoids from added all-trans-retinol [Bernstein, P.S., Law, W.C., & Rando, R.R. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 1849-1853]. The activity was largely localized to the pigment epithelium. Here it is shown that, in the bovine system, the activity resides exclusively in the membranes of the pigment epithelium. Subcellular fractionation does not reveal a particular organelle where the activity resides. Washed bovine pigment epithelium membranes, which are devoid of retinoid redox activity, convert added all-trans-retinol to a mixture of 11-cis-retinol and its palmitate ester. all-trans-Retinal and all-trans-retinyl palmitate are not converted into 11-cis-retinoids by the membranes. The membranes show substantial ester synthetase activity, producing large amounts of all-trans-retinyl palmitate. Diverse chemical reagents, such as ethanol, hydroxylamine, and p-(hydroxymercuri)benzoate, inhibit both ester synthetase and isomerase activities in a roughly parallel fashion, suggesting a possible functional linkage between the two activities.

Topics: Animals; Cattle; Cell Membrane; Diterpenes; Hydroxylamine; Hydroxylamines; Hydroxymercuribenzoates; Kinetics; Pigment Epithelium of Eye; Retinaldehyde; Retinoids; Retinyl Esters; Tritium; Vitamin A

We have previously shown that membranes from the retinal pigment epithelium can transform added all-trans-retinol into a mixture of 11-cis-retinoids, demonstrating the "missing reaction" in the visual cycle for the first time (Bernstein, P. S., Law, W. C., and Rando, R. R. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 1849-1853). In this article, this isomerase activity is further characterized. Double-label experiments with [15-3H]- and [15-14C]all-trans-retinol as the substrate show that the tritium label is retained in the 11-cis-retinol and 11-cis-retinyl palmitate products. This requires that isomerization occur at the alcohol level of oxidation. All-trans-retinyl esters, such as the palmitate, acetate, butyrate, and hexanoate esters, are not directly transformed into their 11-cis counterparts by the membranes. The data are consistent with the presence of an all-trans-retinol isomerase enzyme system or enzyme complex, which produces 11-cis-retinol. Other isomeric retinols were tested for substrate activity. Neither 9-cis-retinol(al) nor 13-cis-retinol were processed by the isomerase. Since the membranes containing the isomerase possess other retinol metabolizing activities, such as retinyl ester synthetase and dehydrogenase activities, further purification was attempted. Appreciable quantities of all detergents tested led to the disappearance of isomerase activity, and high salt or EDTA did not dissociate isomerase activity from the membranes. However, extensive sonication of the membranes did produce a 100,000 x g supernatant fraction of light membranes depleted of other all-trans-retinol processing activities. The isomerase activity in these membranes was saturable with all-trans-retinol, as required for a biologically significant process, and showed a Vmax of 5 pmol/h/mg of protein, a KM of 0.8 microM, and a pH optimum of 8. The isomerase was destroyed by proteinase K, by phospholipase C, by heating, or by ethanol at concentrations greater than 1%. The addition of high energy compounds, such as MgATP, MgGTP, or palmitoyl-CoA, did not appear to stimulate isomerase activity in the 100,000 x g supernatant.

Topics: Animals; cis-trans-Isomerases; Detergents; Diterpenes; Endopeptidase K; Ethanol; Eye; Hydrogen-Ion Concentration; Isomerases; Isomerism; Kinetics; Pigment Epithelium of Eye; Rana pipiens; Retinaldehyde; Retinyl Esters; Serine Endopeptidases; Type C Phospholipases; Vitamin A

In the present study the effect of retinoids on the membrane form of galactosyltransferase was tested. A model system consisting of pure bovine milk galactosyltransferase and phosphatidylserine vesicles was used for this investigation. Retinol, retinal and retinylphosphate were able to overcome the modulating effect of phosphatidylserine, that is, activated the enzyme. Retinoic acid and retinylpalmitate were ineffective in this system.

Topics: Animals; Cattle; Diterpenes; Female; Galactosyltransferases; Kinetics; Liposomes; Milk; Phosphatidylserines; Retinaldehyde; Retinoids; Retinyl Esters; Vitamin A

Using high-performance liquid chromatography, the amounts of all-trans retinol, retinal and retinyl palmitate were measured in the following ocular tissues and fluid of the light (LA) and dark adapted (DA) rabbit: cytosol and membrane fractions of the retina (R/C and R/M), cytosol and membrane fractions of the retinal pigment epithelium (RPE/C and RPE/M), subretinal fluid collected from the inter-photoreceptor matrix (S/R) and the matrix between apical microvilli of the RPE (S/RPE). The total amount of all-trans retinol extracted from LA eyes, 2.74 nmol per eye, was ten times greater than the amount extracted from DA eyes. In the LA eye, most of the all-trans retinol was extracted from the membrane fraction of the retina (67%); in the DA eye, most of the retinol was extracted from the cytosol fraction of the retina (58%). In contrast, the DA eye yielded more all-trans retinal (9.84 nmol) than the LA eye (5.80 nmol) and most of this retinoid was recovered from the cytosol and membrane fractions of the retina. A higher amount of all-trans retinyl palmitate was recovered from the LA eye (5.88 nmol) than the DA eye (2.02 nmol). Although most of this retinyl palmitate was extracted from the cytosol fraction of the RPE (45%, LA eye), appreciable amounts were found in all other ocular compartments. The amount of retinyl palmitate in the LA eye exceeded that of the DA eye in every compartment examined in the present study, suggesting a possible important role of retinyl esters in the visual cycle.

Topics: Animals; Chromatography, High Pressure Liquid; Cytosol; Dark Adaptation; Diterpenes; Membranes; Pigment Epithelium of Eye; Rabbits; Retina; Retinaldehyde; Retinoids; Retinyl Esters; Vitamin A

The all-trans, 9-cis and 11-cis isomers of retinol, retinal and retinyl palmitate were incorporated into unilamellar dioleoyl-lecithin vesicles (liposomes). Isolated frog retinas were inserted into a perfusion chamber and their absorption spectra were recorded (i) in the dark-adapted state, (ii) after exposure to intense light that bleached greater than 95% of rhodopsin and (iii) after liposomes had been added to the perfusate of the bleached preparations. In each experiment, one of the above isomers of the retinol analogs was tested. Regeneration was promoted by the 9-cis and the 11-cis isomer of retinol and of retinal whereas the trans isomers of all compounds and the cis isomers of retinyl palmitate were inactive.

Topics: Animals; Dark Adaptation; Diterpenes; In Vitro Techniques; Isomerism; Liposomes; Photic Stimulation; Rana esculenta; Retina; Retinal Pigments; Retinaldehyde; Retinoids; Retinyl Esters; Rhodopsin; Vitamin A

HPLC (high-performance liquid chromatography) was used to analyse retinyl and 3,4-didehydroretinyl compounds in tissue extracts from goldfish and bullfrog tadpoles. Using silica columns (packed with 10-micron mu Porasil or 5-micron Ultrasphere particles) eluted with n-hexane (containing a small amount of dioxane or diethyl ether), the authentic all-trans retinyl and 3,4-didehydroretinyl palmitates, retinal and 3,4-didehydroretinal, retinol and 3,4-didehydroretinol were completely separated. Liver and eye extracts of the goldfish and bullfrog tadpoles had mainly esterified all-trans retinol and all-trans 3,4-didehydroretinol. In the liver, these vitamin A were conjugated to a number of fatty acids whereas in the eye, principally one fatty acid was used. Moreover, the relative proportions of all-trans retinol and all-trans 3,4-didehydroretinol (obtained by analysing the saponified esters) were significantly different between some of these body compartments.

Topics: Animals; Chromatography, High Pressure Liquid; Diterpenes; Esters; Eye; Goldfish; Larva; Liver; Rana catesbeiana; Retinaldehyde; Retinoids; Retinyl Esters; Vitamin A

The exchange of all-trans retinoids (retinal, retinol, retinylpalmitate) between PC-vesicles, PC-vesicles and liver microsomes or PC-vesicles and rod outer segment membranes is investigated using 11,12(3)H labeled compounds. In the first two systems, retinal and retinol exchange rapidly, retinyl acetate slowly and retinyl palmitate not at all. Rod outer segment membranes however take up relatively small amounts of retinoids (retinylpalmitate less than retinol less than retinal) and rapidly lose 60-90% of their label in the presence of PC-vesicles. E.G. retinoids clearly favour the PC-vesicle membrane. Apparently, rod outer segment membranes have a much lower affinity for retinoids than other artificial or natural membranes investigated so far.

Topics: Animals; Cattle; Diterpenes; Liposomes; Membranes; Microsomes, Liver; Photoreceptor Cells; Retinaldehyde; Retinoids; Retinyl Esters; Rod Cell Outer Segment; Vitamin A

The effect of retinoids (Rds) on cell proliferation was studied in serum-free culture condition, using non-transformed and transformed derivatives of BALB 3T3. Cell proliferation of an SV40-transformed line was inhibited significantly by Rd treatment. However, proliferation of two cell lines that were transformed by a Kirsten and Moloney strain of murine sarcoma virus (MSV) and produced growth factor into culture medium, was remarkably stimulated by Rds. Addition of serum masked both the inhibitory and stimulatory effects of Rds.

Topics: Animals; Blood; Cell Line; Cell Transformation, Viral; Culture Media; Diterpenes; Dose-Response Relationship, Drug; Growth Substances; Kirsten murine sarcoma virus; Mice; Retinaldehyde; Retinyl Esters; Sarcoma Viruses, Murine; Simian virus 40; Tretinoin; Vitamin A

A study has been made of the effects of retinoic acid, retinal, retinol, retinyl palmitate and retinyl acetate on HeLa cell viability. The results obtained show that (i) these cells seem to be more resistant to vitamin A than other cell cultures; (ii) the various vitamin A compounds differ in their inhibitory action on HeLa cells; (iii) the effects of retinoic acid, retinal, retinol and retinyl acetate are cytotoxic, those of retinyl palmitate are always cytolytic.

Topics: Cell Survival; Diterpenes; HeLa Cells; Humans; Retinaldehyde; Retinyl Esters; Tretinoin; Vitamin A

The capacity to generate 11-cis retinal from retinoids arising naturally in the eye was examined in the retina of the bullfrog, Rana catesbeiana. Retinoids, co-suspended with phosphatidylcholine, were applied topically to the photoreceptor surface of the isolated retina after substantial bleaching of the native visual pigment. The increase in photoreceptor sensitivity associated with the formation of rhodopsin, used as an assay for the appearance of 11-cis retinal in the receptors, was analyzed by extracellular measurement of the photoreceptor potential; in separate experiments using the isolated retina or receptor outer segment preparations, the formation of rhodopsin was measured spectrophotometrically. Treatments with the 11-cis isomers of retinal and retinol induced significant increases in both the rhodopsin content and photic sensitivity of previously bleached receptors. The all-trans isomers of retinyl palmitate, retinol, and retinal, as well as the 11-cis isomer of retinyl palmitate, were inactive by both the electrophysiological and spectrophotometric criteria for the generation of rhodopsin. Treatment with any one of the "inactive" retinoids did not abolish the capacity of subsequently applied 11-cis retinal or 11-cis retinol to promote the formation of rhodopsin. The data are discussed in relation to the interconversions of retinoids ("visual cycle of vitamin A") thought to mediate the regeneration of rhodopsin in vivo after extensive bleaching.

Topics: Animals; Diterpenes; Electrophysiology; Photoreceptor Cells; Rana catesbeiana; Retina; Retinaldehyde; Retinyl Esters; Rhodopsin; Vitamin A

Topics: Animals; Cattle; Diterpenes; Erythrocyte Membrane; Erythrocytes; Kinetics; Membrane Proteins; Palmitates; Retinaldehyde; Retinyl Esters; Stereoisomerism; Structure-Activity Relationship; Tritium; Vitamin A

Topics: Alcohols; Animals; Carotenoids; Chickens; Diterpenes; Eggs; Esters; Ethanol; Female; Humans; Liver; Retinaldehyde; Retinyl Esters; Vitamin A