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Chemical Compound Review

AC1NUZ8L     (2E,4Z,6E)-3,7-dimethyl-9- (2,6,6-trimethyl...

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Disease relevance of Retinoic acid


Psychiatry related information on Retinoic acid


High impact information on Retinoic acid

  • Oct-3 has a conserved POU domain, but the remaining part is distinct from other POU domain-containing proteins such as Oct-1 and Oct-2. mRNA of 1.5 kb coding for Oct-3 is abundant in P19 stem cells but is dramatically repressed during RA-induced differentiation [7].
  • Here we report that chick limb buds contain endogenous RA and we show that RA, but not its biosynthetic precursor retinol, forms a concentration gradient across the limb anlage with a high-point in the posterior domain of the limb bud, the part that also contains the ZPA [8].
  • Short-term culture of F9 line cells with RA and dibutyryl cyclic AMP results in a biochemically demonstrable rise in acetylcholinesterase (AChE) activity [9].
  • The NR ligands, vitamin D(3), trans/cis RA, glucocorticoids, and thiazolidines, induce dramatic changes in the physiology of cells harboring high Wnt/beta-catenin/Tcf activity [10].
  • Importantly, BAF180 is recruited to the promoter of these target genes and BAF180 deficiency affects the RA response for CRABPII and RARbeta2 [11].

Chemical compound and disease context of Retinoic acid


Biological context of Retinoic acid

  • Oct-3, which recognizes the typical octamer motif (ATTTGCAT) as well as the AT-rich sequence TTAAAATTCA, is present in P19 stem cells but disappears when the cells are induced to differentiate by retinoic acid (RA) [7].
  • Derepression of RAR signaling by expressing a dominant-negative corepressor resulted in embryos that exhibited phenotypes similar to those treated by RA [17].
  • In many myeloid leukemia cell lines, cyclic adenosine monophosphate (cAMP) triggers growth arrest, cell death, or differentiation, often in synergy with RA [4].
  • Similarly, in RA-sensitive or RA-resistant mouse models of APL, continuous infusions of 8-chloro-cyclic adenosine monophosphate (8-Cl-cAMP) triggered major growth arrest, greatly enhanced both spontaneous and RA- or As(2)O(3)-induced differentiation and accelerated the restoration of normal hematopoiesis [4].
  • In the olfactory pathway, as in the limbs, branchial arches, and heart, mesenchymal/epithelial induction, mediated by retinoic acid (RA), FGF8, sonic hedgehog (shh), and the BMPs, defines patterning, morphogenesis, and differentiation [18].

Anatomical context of Retinoic acid

  • All-trans-retinoic acid (RA) induces striking digit pattern duplications when locally applied to the developing chick limb bud [8].
  • Signaling through RARs is required for patterning along the anteroposterior (A-P) axis, particularly in the hindbrain and posterior, although the absence of RA is required for correct anterior patterning [17].
  • 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 [19].
  • FGF is a general repressor of differentiation, including ventral neural patterning, while RA attenuates Fgf8 in neuroepithelium and paraxial mesoderm, where it controls somite boundary position [20].
  • The F9 murine embryonal carcinoma (EC) cell line, a well established model system for the study of retinoic acid (RA)-induced differentiation, differentiates into cells resembling three types of extra-embryonic endoderm (primitive, parietal and visceral), depending on the culture conditions and RA concentration used [21].

Associations of Retinoic acid with other chemical compounds

  • The TPA-induced as well as the RA- and cAMP-induced decreases in the RNAs hybridizable to pFT27 were regulated at the transcriptional level, whereas similar decreases in the RNAs hybridizable to pFT43 and pFT60 were regulated at the post-transcriptional level [22].
  • These findings suggest testable experiments to determine whether increasing the availability of retinoid in brain, possibly through pharmacologic targeting of the RA receptors and the cytochrome P450 RA-inactivating enzymes, can prevent or decrease amyloid plaque formation [23].
  • Both TPA and 1,25(OH)2D3, which induce HL-60 cells to differentiate to macrophages, resulted in marked increases in c-jun mRNA; while RA and DMSO, which induce HL-60 cells to differentiate to granulocytes, did not greatly alter c-jun mRNA expression [24].
  • Neuraminidase treatment of 125I-labeled surface membrane glycoproteins (SMGs) from wt HL-60 cells converted the two-dimensional gel electrophoretic pattern to one having features in common with RA- and 6TG-resistant cells [25].
  • Treatment of the APL-derived NB4 cells and the RA-resistant subclone NB4R4 with antimony trioxide or potassium antimonyl tartrat triggers the degradation of the fusion protein and the concomitant reorganization of the PML nuclear bodies [26].

Gene context of Retinoic acid

  • Cyp26a1, a gene required for retinoic acid (RA) inactivation during embryogenesis, was previously identified as a potential Tbx1 target from a microarray screen comparing wild-type and null Tbx1 mouse embryo pharyngeal arches (pa) at E9 [27].
  • Constitutive expression of a transfected Hox 1.4 gene under the control of a simian virus 40 promotor leads to differentiated cell morphology similar to that of the RA-induced phenotype and restores the growth-inhibitory effects of RA in N-ras-transformed cells [28].
  • Thus, by specifically blocking the action of the Cyp26 enzymes we can recapitulate many elements of the Tbx1 mutant mouse, supporting the hypothesis that the dysregulation of RA-controlled morphogenesis contributes to the Tbx1 loss of function phenotype [27].
  • The transcript distribution of CRABP I and II is discussed in relation to the teratogenic effects of RA, and compared to the RA-sensitive pattern of expression of other important developmental genes [29].
  • Importantly, overexpressing CBP/p300 or dominant-negative RA receptor-alpha relieved the suppressive effect of RA on PMA-mediated stimulation of the COX-2 promoter [30].

Analytical, diagnostic and therapeutic context of Retinoic acid

  • Using microarray analysis, we identified genes induced by RA, HDACIs, or both together [31].
  • In situ hybridization experiments revealed that the collagen IV(alpha 1) mRNA is restricted to the outer cell layer of F9 cell aggregates regardless of the presence or absence of RA [32].
  • Cultured newt (Notophthalmus viridescens) limb cells were transfected by nuclear microinjection of plasmids which provided RA-sensitive reporter activity that could be normalized for differences in cell recovery and transfection efficiency [33].
  • In addition, Northern blot analysis demonstrated that RA inhibition of E6 and E7 expression was both dose and time dependent [34].
  • RT-PCR experiments and immunoprecipitation assays showed a late but marked increase in the expression of alpha1, alpha2, alpha3, and beta1 chains after IFN-gamma+TNF treatment of LAN-5 cells, and only alpha1 and beta1 chains upon RA induction [35].


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