Disease relevance of Retinoic acid

• In line with this, both RNAi against NFI-A and ectopic expression of miR-223 in acute promyelocytic leukemia (APL) cells enhance differentiation, whereas miR-223 knockdown inhibits the differentiation response to RA [1].
• One of the best characterized cell lines, the embryonal carcinoma stem cell line F9, differentiates after treatment with retinoic acid (RA) and dibutyryl cyclic AMP into parietal endoderm [2].
• P19 teratoma cells differentiate to nerve-like cells in the presence of 5 x 10(-7) M retinoic acid (RA) [3].
• Taken together, these results demonstrate that in vivo activation of cAMP signaling contributes to APL clearance, independently of its RA-sensitivity, thus raising hopes that other myeloid leukemias may benefit from this therapeutic approach [4].
• F9 teratocarcinoma stem cells treated with retinoic acid (RA) and dibutyryl cAMP (but2 cAMP) differentiate into embryonic parietal endoderm [5].

Psychiatry related information on Retinoic acid

• In vivo function of RA-induced neuronal cells was demonstrated by transplantation into the quinolinic acid lesioned striatum of rats (a rat model for Huntington's disease), where cells integrated and survived for up to 6 wk [6].

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

• All-trans-retinoic acid (RA) is active in the treatment of Kaposi's sarcoma (KS), and retinoids inhibit KS cell growth in vitro [12].
• Silencing of the RA induction of RIP140 dramatically enhances and accelerates retinoid receptor transactivation, endogenous expression of other RA target genes, and RA-induced neuronal differentiation and cell cycle arrest in human embryonal carcinoma cells [13].
• The suppressive effect on RA- or DMSO-induced differentiation was unique to HBV, since cell exposure to human cytomegalovirus, another virus that inhibits hematopoiesis, failed to block cellular differentiation [14].
• Within the last several years, research scientists and clinicians have been intrigued with the potential use of an active form of vitamin A, retinoic acid (RA), for the treatment and prevention of emphysema [15].
• Retinoic acid (RA), which reduces the rate of cell proliferation in S91 mouse melanoma clone C2 cells, was found to stimulate the expression of their melanotic phenotype [16].

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].

References