Disease relevance of Rxra

• We examined the effects of different fatty acids (myristic, stearic, oleic, linolenic, and arachidonic acids, EPA, and the peroxisomal proliferator TTA) and several hormones (the glucocorticoid analogue dexamethasone, insulin, and retinoic acid) on the RXRalpha mRNA and protein levels in rat hepatoma cells and cultured hepatocytes [1].
• Increase in the level of RXRalpha in hepatocytes by infection with the RXRalpha-expressing adenovirus resulted in enhancement of the T3-dependent increase in 5'DI mRNA [2].

High impact information on Rxra

• Western blot analyses showed FXR and its heterodimer partner, retinoid X receptor alpha, protein levels are low in the ileum during the suckling period and increase during the third postnatal week [3].
• On a DR4 response element, an OR1 heterodimer with the nuclear receptor retinoid X receptor alpha (RXR alpha) has been described to convey transcriptional activation in both the absence and presence of the RXR ligand 9-cis retinoic acid, the mechanisms of which have remained unclear [4].
• Heterodimeric interaction between retinoid X receptor alpha and orphan nuclear receptor OR1 reveals dimerization-induced activation as a novel mechanism of nuclear receptor activation [4].
• Transfection with an expression vector for the retinoid X receptor alpha (RXR alpha) increases transactivation by T3 and RA but does not abolish the inhibition caused by the vitamin [5].
• The PPAR-gamma/retinoid X receptor-alpha heterodimer was bound to the element and activated the LGK promoter [6].

Biological context of Rxra

• However, as a heterodimer with retinoid X receptor alpha (RXR alpha), PPAR alpha regulates transcription of genes involved in oxidative stress, cell proliferation and apoptosis [7].
• Transient transfection assays indicated that the (-4551)UCP1-CAT construct, containing the 5'-regulatory region of the rat ucp-1 gene, was activated by PPARalpha co-transfection in a dose-dependent manner and this activation was potentiated by Wy 14,643 and retinoid X receptor alpha [8].
• To delineate mechanisms involved in retinoid-mediated control of cardiac gene expression, the regulatory effects of the retinoid X receptor alpha (RXR alpha) on atrial naturietic factor (ANF) gene transcription was investigated [9].
• The RXR alpha-mediated repression mapped to the proximal 147 bp of the rat ANF promoter, a region lacking a consensus retinoid response element but containing several known cardiogenic cis elements including a well characterized GATA response element [9].
• Glutathione S-transferase "pull-down" assays revealed that RXR alpha interacts directly with GATA-4, in a ligand-independent manner, via the DNA binding domain of RXR alpha and the second zinc finger of GATA-4 [9].

Anatomical context of Rxra

• Co-transfection of liganded RXR alpha and the known cardiac-enriched GATA-4 repressor, FOG-2, resulted in additive repression of GATA-4 activity in ventricular myocytes [9].
• Liganded RXR alpha repressed the activity of a heterologous promoter-reporter construct containing GATA-response element recognition sites in cardiac myocytes but not in several other cell types, suggesting that additional cardiac-enriched factors participate in the repression complex [9].
• Importantly, whereas expression of PPARgamma/RXRalpha attenuates GSIS, the expression of PPARalpha/RXRalpha potentiates GSIS in rat islets and INS-1E cells without affecting the mitochondrial membrane potential [10].
• Distribution of mRNAs encoding the peroxisome proliferator-activated receptor alpha, beta, and gamma and the retinoid X receptor alpha, beta, and gamma in rat central nervous system [11].
• We describe here a new peroxisome proliferator-response element located in the intron 3 (+1422/+1434) that binds in vitro the PPARalpha/retinoid X receptor alpha heterodimer and confers the induction by PPARalpha in transfection assays [12].

Associations of Rxra with chemical compounds

• Placental expression of Ppara, Ppard, and Rxra was unaffected by dexamethasone treatment [13].
• Retinoid X receptor alpha represses GATA-4-mediated transcription via a retinoid-dependent interaction with the cardiac-enriched repressor FOG-2 [9].
• In addition, RXR alpha was found to bind FOG-2, in a 9-cis-RA-dependent manner [9].
• Although overexpression of nSREBP1c significantly reduced PUFA inhibition of S14CAT, overexpression of other factors that induced S14CAT activity, such as steroid receptor co-activator 1 or retinoid X receptor alpha, had no effect on S14CAT PUFA sensitivity [14].
• Two nuclear retinoid receptors that were expressed in bacteria, retinoic acid receptor-gamma and retinoid X receptor-alpha, were found to bind specifically to a double-stranded oligonucleotide containing the RARE in gel mobility shift assays [15].

Physical interactions of Rxra

• In the presence of RA, the coactivators SRC-1 and GRIP-1 formed complexes with RAR beta and RXR alpha which are bound to an oligonucleotide specifying a RARE site in the promoter [16].

Regulatory relationships of Rxra

• The peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear receptor super-family of ligand-activated transcription factors and it functions as an obligate heterodimer with retinoid X-receptor alpha RXRalpha [17].

Other interactions of Rxra

• Results from this study suggest that alterations in peroxisomal metabolism observed in the senescent liver may be a result of the decline in the availability of RXR alpha receptor, and not the primary PPAR alpha receptor [7].
• Although the expression of PPARalpha/RXRalpha leads to the induction of UCP2 mRNA and protein, this is not accompanied by reduced hyperpolarization of the mitochondrial membrane, indicating that under these conditions, increased UCP2 expression is insufficient for dissipation of the mitochondrial proton gradient [10].
• These results suggest that the possible perinatal RA production by RALDHs might regulate various RA-target genes including CRBPII and RARalpha through RXRalpha or HNF-4 in the small intestine [18].
• Whereas DEX increased the amount of RXRalpha mRNA, it did not affect the expression of other possible factors such as steroid receptor coactivator-1 and the binding protein of cAMP response element-binding protein [2].
• Electrophoretic mobility shift assay using a putative nuclear receptor-binding element on rat HNF-1 alpha gene revealed that HNF-4 homodimer, but not RXRalpha homodimer, bound to this element [19].

Analytical, diagnostic and therapeutic context of Rxra

• Gel mobility shift assays demonstrated that CERIP interacted with RXRalpha and RXRgamma but not with RXRbeta, indicating a receptor subtypespecific binding preference and suggesting an RXR AB region-dependent interaction [20].
• Retinoid receptor expression was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) using subtype-specific primers and demonstrated expression of retinoic acid receptor alpha (RAR-alpha), RAR-beta and retinoid X receptor alpha (RXR-alpha) [21].

References