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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin A and its derivatives, the retinoids, are essential regulators of many important biological functions, including cell growth and differentiation, development, homeostasis, and carcinogenesis. Natural retinoids such as all-trans retinoic acid can induce cell differentiation and inhibit growth of certain cancer cells. We recently identified a novel class of synthetic retinoids with strong anti-cancer cell activities in vitro and in vivo which can induce apoptosis in several cancer cell lines. Using an electrophoretic mobility shift assay, we analyzed the DNA binding activity of several transcription factors in T cells treated with apoptotic retinoids. We found that the DNA binding activity of the general transcription factor Sp1 is lost in retinoid-treated T cells undergoing apoptosis. A truncated Sp1 protein is detected by immunoblot analysis, and cytosolic protein extracts prepared from apoptotic cells contain a protease activity which specifically cleaves purified Sp1 in vitro. This proteolysis of Sp1 can be inhibited by N-ethylmaleimide and iodoacetamide, indicating that a cysteine protease mediates cleavage of Sp1. Furthermore, inhibition of Sp1 cleavage by ZVAD-fmk and ZDEVD-fmk suggests that caspases are directly involved in this event. In fact, caspases 2 and 3 are activated in T cells after treatment with apoptotic retinoids. The peptide inhibitors also blocked retinoid-induced apoptosis, as well as processing of caspases and proteolysis of Sp1 and poly(ADP-ribose) polymerase in intact cells. Degradation of Sp1 occurs early during apoptosis and is therefore likely to have profound effects on the basal transcription status of the cell. Interestingly, retinoid-induced apoptosis does not require de novo mRNA and protein synthesis, suggesting that a novel mechanism of retinoid signaling is involved, triggering cell death in a transcriptional activation-independent, caspase-dependent manner.
Mol Cell Biol 1997 Nov
PMID:Retinoid-induced apoptosis and Sp1 cleavage occur independently of transcription and require caspase activation. 934 96

The effect of retinol deficiency and curcumin/turmeric on lipid peroxidation and fatty acid profile was studied in liver, kidney, spleen and brain microsomes of rats. Results revealed an increase in lipid peroxidation in retinol deficient liver by 32%, kidney 30%, spleen 24% and brain 43% compared to the controls. Feeding 0.1% curcumin or turmeric for three weeks in diet to retinol deficient rats reduced the lipid peroxidation respectively to 12.5 or 22.6%, in liver, 23.7 or 24.1% in kidney, 14.4 or 18.0% in spleen and 16.0 or 31.4% in brain. Retinol deficiency lead to a reduction in the essential fatty acids. In liver C18:1 showed a reduction by 45.6%, C18:2 by 31.6% and C20:4 by 22.8%. In kidney C18:1 was reduced by 33.6%, 18:2 by 24.6% and 20:4 by 13.7%. In spleen and brain C18:1 showed a reduction by 10.2% and 33.9%, C18:2 by 37.9% and 12.1% and C20:4 by 15.7% and 35.3% respectively. Curcumin and turmeric fed group showed a significant increase in the abnormally reduced fatty acid levels.
Mol Cell Biochem 1997 Oct
PMID:Influence of retinol deficiency and curcumin/turmeric feeding on tissue microsomal membrane lipid peroxidation and fatty acids in rats. 935 32

Low-density lipoprotein (LDL) cholesterol participates in the atherosclerotic process only after oxidative modification (o-LDL). Persons with elevated body iron concentrations are at higher risk of atherosclerosis. Iron in vitro is capable of oxidizing LDL, but it is unknown whether or not high dietary iron concentrations alter LDL in vivo. The aim of this study was, therefore, to investigate (i) whether dietary iron concentrations cause LDL-cholesterol oxidation and (ii) whether antioxidants can prevent such changes. Rats received diets differing only in iron concentration: 35 mg/kg, 150 mg/kg or 300 mg/kg diet. A LDL-VLDL particle was isolated and the following parameters measured: malondialdehyde and lipid hydroperoxide concentrations (as an indication for lipid peroxidation); alpha-tocopherol and retinol concentrations (as antioxidants); protein sulfhydryl and carbonyl concentrations (as an indication of protein modification); agarose gel electrophoresis and cholesterol/protein ratio. Dietary iron increased LDL-VLDL lipid peroxidation (malondialdehyde and lipid hydroperoxide concentrations), protein modification (sulfhydryl concentration), agarose migration distance and band width as well as cholesterol/protein ratio. Increased quantities of dietary iron led to a higher degree of oxidative change in LDL-VLDL. Lipid peroxidation, as well as protein modification, occurred, suggesting apoB changes. This was probably due to diminished antioxidant concentrations of alpha-tocopherol and beta-carotene. Antioxidant supplementation (alpha-tocopherol and beta-carotene), however, prevented all the above changes and could be helpful in the prevention of atherosclerosis.
Res Commun Mol Pathol Pharmacol 1998 Jan
PMID:Dietary iron concentration alters LDL oxidatively. The effect of antioxidants. 952 56

High body iron and LDL-cholesterol concentrations, and antioxidant deficiency, are regarded as risk factors for ischemic heart disease. Iron is well known for causing oxidative damage and antioxidants for their beneficial effects on radical scavenging. It is, however, unknown whether or not dietary iron causes depletion of plasma antioxidants; causes lipid peroxidation; alters HDL- and LDL-cholesterol, and triglyceride concentrations. Rats received diets differing only in iron concentration--15 mg/Kg, 35 mg/Kg, 150 mg/Kg or 300 mg/Kg diet. The second group of rats received antioxidants (alpha-tocopherol and beta-carotene) in their drinking water. Increasing dietary iron increased plasma lipid hydroperoxide and LDL-cholesterol concentrations, but did not affect HDL-cholesterol or triglyceride concentrations. It decreased antioxidants, alpha-tocopherol and retinol. Antioxidant supplementation inhibited the above changes.
Res Commun Mol Pathol Pharmacol 1998 May
PMID:Dietary iron elevates LDL-cholesterol and decreases plasma antioxidant levels: influence of antioxidants. 966 68

Physiological responses due to steroid hormones and retinoids are regulated by their cognate receptors and dehydrogenases. The origins of either regulatory mechanism are not fully understood. Here we examine the origins of the human 11beta-hydroxysteroid dehydrogenase-type 2, which regulates access of glucocorticoids to cells, and 17beta-hydroxysteroid dehydrogenase-type 2, which regulates access of androgens and estrogens to cells. Sequence comparisons trace their ancestry to homologs in Caenorhabditis elegans. These C. elegans proteins most closely resemble mammalian all-trans and 11-cis-retinol dehydrogenases. The similarity is sufficient -37% to 43% identity to suggest that one or more of the C. elegans homologs metabolizes a retinoid. Receptors for retinoids, but not for androgens, estrogens or glucocorticoids have been identified in C. elegans, suggesting that retinoid-mediated gene transcription is more ancient than that for adrenal and sex steroids. We propose that the hydroxysteroid dehydrogenase-type 2 mechanism for regulating the androgen, estrogen and glucocorticoid concentrations in mammals descended from that for regulating retinoid concentrations. Interestingly, E. coli contains a protein with strong sequence similarity to mammalian retinol dehydrogenases. Sequence comparisons and phylogenetic analysis indicate that the E. coli protein may be an example of horizontal transfer from a eukaryote ancestor.
J Steroid Biochem Mol Biol 1998 Sep
PMID:Evolution of mammalian 11beta- and 17beta-hydroxysteroid dehydrogenases-type 2 and retinol dehydrogenases from ancestors in Caenorhabditis elegans and evidence for horizontal transfer of a eukaryote dehydrogenase to E. coli. 974 41

Vitamin A and its derivatives (retinoids) have profound effects on the proliferation and differentiation of many cell types and are involved in a diverse array of developmental and physiological regulatory processes, including those responsible for the development of the mature nervous system. Retinoid signals are mediated by retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs), which show distinct spatio-temporal patterns of expression during development and in adult tissues. We have used SK-N-BE2(c) neuroblastoma cells to study the effects of reciprocal regulation of expression of various RARs. We show that in these cells RARgamma1 acts as a repressor of RARbeta2 transcription in the absence of an agonist. In the presence of RA, the expression of RARgamma1 is reduced and that of RARbeta2 is induced. Overexpression of RARgamma1 neutralizes the effects of RA on RARbeta induction. Expression of an RARgamma1-specific antisense construct leads to the constitutive expression of RARbeta2. Although both overexpression of RARgamma1 and its reduction of expression can result in inhibition of cell proliferation, they induce different morphological changes. Reduction of RARgamma1 (and induction of RARbeta) leads to increased apoptosis, whereas RARgamma1 overexpression leads to differentiation in the absence of apoptosis. Thus, RARgamma1 appears to control a differentiation-apoptosis switch in SK-N-BE2(c) neuroblastoma cells.
Mol Cell Biol 1998 Nov
PMID:Retinoic acid receptor gamma1 (RARgamma1) levels control RARbeta2 expression in SK-N-BE2(c) neuroblastoma cells and regulate a differentiation-apoptosis switch. 977 64

Liver is a major site of retinoid metabolism and storage, and more than 80% of the liver retinoids are stored in hepatic stellate cells. These cells represent less than 1% of the total liver protein, reaching a very high relative intracellular retinoid concentration. The plasma level of retinol is maintained close to 2 microM, and hepatic stellate cells have to be able both to uptake or to release retinol depending upon the extracellular retinol status. In view of their paucity in the liver tissue, stellate cells have been studied in primary cultures, in which they loose rapidly the stored lipids and retinol, and convert spontaneously into the activated myofibroblast phenotype, turning a long-term study of their retinol metabolism impossible. We have analyzed the retinol metabolism in the established GRX cell line, representative of stellate cells. We showed that this cell line behaves very similarly, with respect the retinol uptake and release, to primary cultures of hepatic stellate cells. Moreover, we showed that the cellular retinol binding protein (CRBP-I) expression in these cells, relevant for both uptake and esterification of retinol, responds to the extracellular retinol status, and is correlated to the retinol binding capacity of the cytosol. Its expression is not associated with the overall induction of the lipocyte phenotype by other agents. We conclude that the GRX cell line represents an in vitro model of hepatic stellate cells, and responds very efficiently to wide variations of the extracellular retinol status by autonomous controls of its uptake, storage or release.
Mol Cell Biochem 1998 Oct
PMID:Retinol uptake and metabolism, and cellular retinol binding protein expression in an in vitro model of hepatic stellate cells. 978 38

Retinol stimulates the formation of transition vesicles in situ and in all free systems based on rat liver. The stimulation is on vesicle formation from transitional endoplasmic reticulum and not on vesicle fusion with donor membranes. Vesicle budding in the cell free system requires a nucleoside triphosphate and is sensitive to inhibition by thiol reagents. In this report we develop and test a model whereby a retinol-modulated NADH:protein disulfide reductase (NADH oxidase) with protein disulfide-thiol interchange activity is implicated in the vesicle budding mechanism. The protein has the ability to restore activity to scrambled, inactive RNase A and is stimulated or inhibited by retinol depending on the redox environment. Under reducing conditions and in the presence of a chemical reductant such as GSH, the partial reaction stimulated by retinol appears to be the oxidation of membrane thiols. This is the first report of an enzymatic mechanism to explain specific retinol effects both in vivo and in vitro on membrane trafficking not given by retinoic acid.
Mol Cell Biochem 1998 Oct
PMID:A molecular basis for retinol stimulation of vesicle budding in vivo and in vitro. 978 45

Retinoids influence proliferation and differentiation in transformed thyroid cell lines. Retinoids are able to damage cells by destabilizing lysosomal membranes and induce apoptosis in certain cell lines. In normal thyrocytes retinol modulates iodine metabolism. At concentrations higher than 50x10(-6) M retinoids are cytotoxic for normal (not transformed) thyroid cells. The mechanism of this cytotoxicity is unknown. We studied the effect of 7-80x10(-6) M retinol on porcine follicular thyrocytes in culture. In order to differentiate between membrane-destabilizing effects and apoptosis we investigated cultures after incubation with retinol by light- and electron-microscopy and by labeling of potential nicks in the DNA helix by terminal deoxynucleotidyltransferase-dUTP mediated DNA nick end labeling. We conclude that the observed cytotoxicity is caused mainly by the induction of apoptosis.
J Mol Med (Berl) 1999 Jan
PMID:Effects of retinol on follicular porcine thyrocytes in culture. 993 Sep 61

Serum retinol, retinyl palmitate, beta-carotene, cryptoxanthin, lutein, alpha-tocopherol and gamma-tocopherol were measured in 18 captive Humboldt penguins (Spheniscus humboldti) prior to and following the removal of Columbia River (CR) smelt (Thaleichthys pacificus) from the diet. Dietary vitamin A was reduced from 59.8 to 13.5 IU g-1 (dry matter basis) when CR smelt was removed from the diet. Minimal changes were noted in dietary vitamin E. Serum samples Without-CR smelt had significantly lower circulating retinol (1.19 +/- 0.09 vs. 1.94 +/- 0.08 micrograms ml-1) and retinyl palmitate (0.033 +/- 0.012 vs. 0.105 +/- 0.004 microgram ml-1) compared to samples With-CR. The Without-CR smelt diet resulted in increased serum alpha-tocopherol from 26.4 +/- 0.94 to 39.1 +/- 3.72 micrograms ml-1. More serum samples taken Without-CR smelt had detectable levels of gamma-tocopherol than those With-CR smelt. Serum lutein was higher for the samples taken Without versus With-CR smelt. Serum cryptoxanthin did not differ. beta-Carotene was not detected. Data indicate that high levels of dietary vitamin A can affect circulating levels of retinol, retinyl palmitate and vitamin E. Thus, dietary vitamin A and the interrelationship between vitamins A and E should be considered when assessing captive penguins.
Comp Biochem Physiol A Mol Integr Physiol 1998 Dec
PMID:Influence of dietary vitamins A and E on serum alpha- and gamma-tocopherols, retinol, retinyl palmitate and carotenoid concentrations in Humboldt penguins (Spheniscus humboldti). 1004 86


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