Receptor retinoid acid

Missbach, M., Jagher, B., Sigg, I., Nayeri, S., Carlberg, C., and Wiesenberg, I. (1998) Thiazolidine diones, specific ligands of the nuclear receptor retinoid Z receptor/retinoid acid receptor-related orphan receptor a with potent antiarthritic activity. J. Biol. Chem. 271, 13515-13522. 

Issemann I, Prince RA, Tugwood JD, et al. 1993. The peroxisome proliferator-activated receptor retinoid X receptor heterodimer is activated by fatty acids and fibrate hypolipidaemic drugs. J Mol Endocrinol 1137-47. 

Martin, G., Poirier, H., Hennuyer, N., Crombie, D., Fruchart, J. C., Heyman, R. A., Besnard, P., and Auwerx, J. (2000). Induction Of The Fatty Acid Transport Protein 1 and Acyl-Coa Synthase Genes by Dimer-Selective Rexinoids Suggests That the Peroxisome Proliferator-Activated Receptor-Retinoid X Receptor Heterodimer is Their Molecular Target./ Bid. Chem. 275, 12612-12618. 

Retinoid acids (RAs), the active retinoid derivatives of vitamin A, regulate complex gene networks. The pleiotropic effects of active retinoids are transduced by their cognate nuclear receptors, retinoid X receptors (RXRs) and retinoic add receptors... 

The ligand binding pocket of USP is filled by a fortuitous phospholipid co-purified and co-crystallized with the USP LBD that was fiirther characterized by mass-spectroscopic and chemical analysis [57]. In a similar way, recent crystallographic investigations of the retinoid-acid related orphan receptor (3 (ROR (3) [58] and of the heterodimeric complex RARa/RXRa [30] revealed an E.coli endogeneous fatty acid in the ROR (3 and in the RXRa subunit, respectively. 

H. Chiba, J. Clifford, D. Metzger, and P. Chambon. Distinct retinoid X receptor-retinoic acid receptor heterodimers are differentially involved in the control of expression of retinoid target genes in F9 embryonal carcinoma cells. Mol Cell Bid, 17 (6), 3013-3020, 1997. 

It is assumed that some compounds of this group (AHTN and ATTN) may bind to the retinoid acid receptor (RAR) or retinoid X receptor (RXR) because their structure shows some similarity with synthetic RXR ligands [364,365]. The RAR and RXR belong to the steroid/thyroid hormone nuclear receptor super family. They play a central role in the regulation of many intracellular receptor pathways [366]. However, all these assumptions and predictions, especially the predicted high bioconcentration potential of the PMFs, have to be investigated experimentally. 

Unlike its geometric isomer all /ram-retinoid acid, which binds only RAR receptors, alitretinoin is a ligand for both RAR and RXR. It has been called a "pan-agonist.". since it binds all retinoid receptors. Because of this ability it has been proposed that alitretinoin may be more potent and thus more effective than other retinoids. ... 

Keller, H., Dreyer, C., Medin, J., Mahfoudi, A., Ozato, K., and Wahli, W. (1993). Patty acids and retinoids control Upid metaboUsm through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers. Proc Natl Acad Sci USA 90, 2160-2164. 

Tsukada, M., Schroder, M., Roos, T.C., Chandraratna, R.A., Reichert, U., Merk, H.F., Orfanos, C.E. and Zouboulis, C.C. (2000) 13-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors. The Journal of Investigative Dermatology, 115, 321-327. 

FIGURE 16.14 Retinoid acid receptor agonist. Enzymatic preparation of 2-(R)-hydroxy-2-(l 2 3 4 -tetrahydro-l l 4 4 -tetramethyl-6 -naphthalenyl)acetate 54. 

Retinoids failed to activate NADPH oxidase in dibutyryl cAMP differentiated HL-60 cells (Seifert and SCHACHTELE 1988). In HL-60 cells retinoids have been found to potentiate formyl-methionyl-leucyl-phenylalanine-induced and phorbol myrist-ate acetate-induced 02 formation (Seifert and SchAchtele 1988). Using receptor specific retinoid analogues it was demonstrated that retinoid X receptor-retinoic acid receptor heterodimers mediate retinoid-induced differentiation of HL60 cells, while retinoid X receptor-retinoid X receptor homodimers mediate subsequent retinoid-mediated apoptosis (Nagy et al. 1995, Kizaki et al. 1996). 

In untreated U937 (human monoblastic leucaemia cell line) cells retinoid receptor-a mRNA levels increased after induction of differentiation via phorbol myristate acetate (Brown et al. 1997). Using plasmids containing sense or antisense retinoid receptor-a sequences under the control of an inducible promoter. Brown et al. generated stable transfected cell lines which expressed either increased or decreased levels of retinoid X receptor-a, respectively. The sense cell lines showed an increased sensitivity to 9-cis retinoid acid, while the antisense cell lines presented decreased sensitivity. Combined 9-cis retinoic acid and la,25-dihydroxy... 

Durand B, Saunders M, Gaudon C, Roy B, Losson R, Chambon P (1994) Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoid acid receptor presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element. EMBO J 13 5370-5382... 

Xiao JH, Durand B, Chambon P, Voorhees JJ (1995) Endogenous retinoic acid receptor-retinoid X receptor heterodimers are the major functional forms regulating retinoid-responsive elements in adult human ker-atinocytes. J Biol Chem 270 3001-3011... 

Kurokawa R, Soderstrom M, Hdrlen A, Halachmi S, Brown M, Rosenfeld MG, Glass CK (1995) Polarity-specific activities of retinoid acid receptors determined by a co-repressor. Nature ill 451-453 Lala DS, Mukheijee R, Schulman IG, Canan Koch SS, Dardashti LJ, Nadzan AM, Croston GE, Evans RM, Heyman RA (1996) Activation of specific RXR heterodimers by an antagonist of RXR homodimers. Nature... 

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

Agents which enhance the host s response against neoplasias or force them to differentiate are termed biological response modifiers. Examples include interleukin 2 which is used to treat renal cell carcinoma, interferon a which is active against hematologic neoplasias, and tretinoin (all-trans retinoic acid) which is a powerful inducer of differentiation in certain leukemia cells by acting on retinoid receptors. Side effects include influenza like symptoms, changes in blood pressure and edema. 

Proton Pump Inhibitors and Acid Pump Antagonists retinoid X receptor (RXR) and is also activated by various lipophilic compounds produced by the body such as bile acids and steroids. PXR heterodimerized with RXR stimulates the transcription of cytochrome P450 3A monooxygenases (CYP3A) and other genes involved in the detoxification and elimination of the... 

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