Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of retinoids on fetal lung development in the rat. The concentration of retinyl palmitate increased rapidly to a peak on day 17 of gestation and decreased to a minimum on day 21 of gestation; there was a slight increase after birth. Retinoid acid receptor (RAR)-alpha and -beta mRNA were detected in all samples obtained from perinatal and adult rat lung, and only a trace of RAR-gamma mRNA was detected in the fetuses on days 15, 17 and 19 of gestation and in the adults by reverse transcriptase-polymerase chain reaction. After a maternal retinol deficiency of 28 days' duration, fetal body and lung weights were significantly lower than those of controls; the concentrations of retinyl palmitate and phosphatidylcholine (PC) in the lung after a maternal retinol deficiency of 14, 21, or 28 days were significantly lower than those of controls. Expression of RAR-beta mRNA in the group with 28-day retinol deficiency was lower than in controls, that of RAR-alpha mRNA was increased and that of RAR-gamma mRNA was not influenced by retinol deficiency. The rate of choline incorporation into PC in fetal lung explants was significantly higher in the group treated with retinoic acid (RA) than in controls. RA enhanced the effect of epidermal growth factor on choline incorporation and prevented that of dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effect of retinoids on fetal lung development in the rat. 754 61

Retinoids are biologic response modifiers that are present in normal skin and may possibly be perturbed in carcinogenesis. To examine this possibility in human skin, we analyzed vitamin A and cytosolic retinoid binding proteins (cellular retinol binding protein and cellular retinoic acid binding protein [CRABP]) in a total of 38 non-melanoma skin tumors and 25 healthy skin samples using high performance liquid chromatography, radioligand electrophoresis, and reverse transcriptase-polymerase chain reaction. The mean +/- SEM retinol concentration was normal in basal cell carcinoma (0.60 +/- 0.10 microM) and seborrheic keratosis (0.47 +/- 0.07 microM), but increased in keratoacanthoma (1.60 +/- 0.41 microM) and squamous cell carcinoma (1.17 +/- 0.28 microM) (p < 0.05 for both). Also, the concentrations of 3,4-didehydroretinol, a major vitamin A metabolite produced in human skin, were markedly elevated (6-7 times normal) in keratoacanthoma and squamous cell cancer. All types of tumors showed moderately increased levels of cellular retinol binding protein. In addition, keratoacanthoma and squamous cell cancer showed markedly increased levels (6-7 times normal) of CRABPII protein. Transcriptional activity of the CRABPII gene was demonstrated in both normal and neoplastic epidermis, but clear CRABPI mRNA expression was found only in basal cell carcinoma. The data indicate that characteristic perturbations of the vitamin A and retinoid binding protein levels occur in squamous cell-derived skin tumors, but whether these reflect intrinsic errors in retinoid metabolism or are secondary to abnormal cellular differentiation is unknown.
...
PMID:Increased concentrations of 3,4-didehydroretinol and retinoic acid-binding protein (CRABPII) in human squamous cell carcinoma and keratoacanthoma but not in basal cell carcinoma of the skin. 861 41

Retinoic acids, vitamin A-related compounds, are known to be inhibitors of telomerase. We found that fucoxanthin from the sea alga Petalonia bingamiae is a potent inhibitor of mammalian replicative DNA polymerases (i.e., pol alpha, delta and epsilon). Since fucoxanthin is a carotenoid (provitamin A-related) compound, we characterized the biochemical modes of vitamin A-related compounds including vitamin A and provitamin A in this report. Subsequently, we found that fucoxanthin, all-trans retinal (RAL, vitamin A aldehyde) and all-trans retinoic acid (RA, vitamin A acid) inhibited the activities of replicative DNA polymerases with IC(50) values of 18-190, 14-17 and 8-30 microM, respectively. On the other hand, all-trans retinol (vitamin A) did not influence any of the DNA polymerase activities. RA inhibited not only the activities of pol alpha, delta and epsilon with IC(50) values of 30, 28 and 8 microM, respectively, but of pol beta with an IC(50) value of 27 microM. The tested vitamin A-related compounds did not influence the activities of DNA polymerases from a higher plant, cauliflower, prokaryotic DNA polymerases, or DNA metabolic enzymes such as human immunodeficiency virus type 1 reverse transcriptase, T7 RNA polymerase and bovine deoxyribonuclease I. RAL and RA should be called selective inhibitors of mammalian DNA polymerases including telomerase, and RAL was a specific inhibitor of mammalian replicative DNA polymerases. As expected from these results in vitro, some of them could prevent the growth of NUGC-3 human gastric cancer cells, and especially RAL was a potent antineoplastic agent with an LD(50) value of 19 microM. The cells were halted at G1 phase in the cell cycle by RAL.
...
PMID:Vitamin A-related compounds, all-trans retinal and retinoic acids, selectively inhibit activities of mammalian replicative DNA polymerases. 1195 16

Retinyl ester, the most abundant form of vitamin A (retinol), is synthesized by the enzyme lecithin:retinol acyltransferase (LRAT). Previously, we cloned a 2.5 kb LRAT cDNA from rodent liver which codes for functional LRAT activity. However, Northern blots of tissues probed with the 2.5 kb cDNA revealed the presence of a larger transcript of approximately 5 kb as well as several smaller transcripts. To elucidate the nature of the large LRAT transcript, a high-molecular-mass adrenal gland cDNA library was screened. Two similar clones of 3962 and 3187 nt were identified which appeared to be part of the 3'-untranslated region (UTR) of a 5358 nt LRAT mRNA. The 5.3 kb cDNA was then amplified from liver by reverse transcriptase PCR (RT-PCR) and demonstrated to encode functional LRAT activity. The 3'-UTR of the 5.3 kb cDNA contains several AAUAAA polyadenylation signals. Analysis of the 3' ends of LRAT mRNA transcripts from liver, intestine and testis showed the usage of both canonical and non-canonical polyadenylation signals. To further analyse the LRAT mRNAs expressed in vivo, Northern blot analysis was performed using four probes spanning sections from the 5' end to the distal 3' end of the 5.3 kb LRAT cDNA. The results show that the major 5.3 kb transcript uses the canonical signal AAUAAA located at nt 5308, and the major short transcript of approximately 1.5 kb uses the non-canonical signal AUUAAA located at nt 1330. The 5.3 kb LRAT transcript was predominant in the liver of retinoic acid-repleted vitamin A-deficient rats, coincident with increased quantitative expression of LRAT mRNA and enzyme activity. The differential usage of these polyadenylation signals can explain the presence of multiple LRAT mRNA transcripts which are expressed in different tissue-specific patterns.
...
PMID:Cloning and molecular expression analysis of large and small lecithin:retinol acyltransferase mRNAs in the liver and other tissues of adult rats. 1220 19

Antibody against adult Ancylostoma caninum excretory-secretory (ES) products was used to immunoscreen a cDNA expression library leading to the isolation of cDNAs encoding putative hookworm fatty-acid and retinol-binding proteins. Ac-far-1 and Ac-far-2 cDNAs encode open reading frames corresponding to approximately 20kDa proteins with 91 percent amino acid identity. Ac-FAR-1 and Ac-FAR-2 exhibit clear similarities to other FARs of parasitic nematodes, most closely to two of the FAR proteins of Caenorhabditis elegans (Ce-FAR-1 and Ce-FAR-2). By reverse transcriptase polymerase chain reaction (RT-PCR) assay, Ac-far-1 mRNA was detected in both adult and third-stage larvae of A. caninum. However, the respective proteins were detectable by immunoblot only in adult hookworm ES products and adult extracts. Using fluorescence-based binding assays, bacterial recombinant Ac-FAR-1 was found to bind fatty acids and retinol (Vitamin A) with dissociation constants in the micromolar region. Circular dichroism spectra indicated that Ac-FAR-1 possesses a high level of alpha-helix, similar to Ov-FAR-1 from Onchocerca volvulus. This is the first demonstration of a functional FAR secreted by adult hookworms and provides further evidence that FAR proteins secreted by parasitic nematodes are crucial to parasitism.
...
PMID:Ac-FAR-1, a 20 kDa fatty acid- and retinol-binding protein secreted by adult Ancylostoma caninum hookworms: gene transcription pattern, ligand binding properties and structural characterisation. 1255 85

Livers of aryl hydrocarbon receptor (AHR)-null mice have high levels of retinoic acid (RA), retinol, and retinyl palmitate. Hepatic accumulation of RA in these mice may be responsible in part for the hepatic phenotype characterized by small liver size and fibrosis. The increased levels of hepatic RA may be due to decreased metabolism of RA to 4-hydroxyretinoic acid. To identify the P450 isoform(s) involved in RA metabolism, liver microsomes from AHR-null and wild-type mice were subjected to Western blotting and probed with antibodies to rat P450s that cross-react with murine forms. Signal intensity in Western blots probed with anti-rat CYP2C6 antibodies correlated with levels of RA 4-hydroxylation. Furthermore, this anti-rat CYP2C6 antibody inhibited RA 4-hydroxylase activity of wild-type mouse liver microsomes to the levels of AHR-null mouse liver. When used to screen a mouse liver cDNA expression library, this antibody exclusively recognized the murine P450 CYP2C39. Catalytic assays of five recombinant mouse CYP2Cs expressed in Escherichia coli revealed that only CYP2C39 was competent for RA 4-hydroxylation (K(m) = 812.3 nm and V(max) 47.85 (fmol/min/pmol P450)). Real time reverse transcriptase-PCR used to assess the Cyp2C39 mRNA expression showed decreased levels (30%) of this transcript in AHR-null compared with wild-type liver, consistent with decreased protein levels observed by Western blot analysis using an antibody to a CYP2C39-specific peptide. These data show that CYP2C39 catalyzes RA catabolism and thus possibly controls RA levels in mouse liver. Down-regulation of Cyp2C39 is hypothesized to be responsible for the liver phenotype in the AHR-null mouse.
...
PMID:Mouse liver CYP2C39 is a novel retinoic acid 4-hydroxylase. Its down-regulation offers a molecular basis for liver retinoid accumulation and fibrosis in aryl hydrocarbon receptor-null mice. 1462 88

Development of normal colon epithelial cells proceeds through a systematic differentiation of cells that emerge from stem cells within the base of colon crypts. Genetic mutations in the adenomatous polyposis coli (APC) gene are thought to cause colon adenoma and carcinoma formation by enhancing colonocyte proliferation and impairing differentiation. We currently have a limited understanding of the cellular mechanisms that promote colonocyte differentiation. Herein, we present evidence supporting a lack of retinoic acid biosynthesis as a mechanism contributing to the development of colon adenomas and carcinomas. Microarray and reverse transcriptase-PCR analyses revealed reduced expression of two retinoid biosynthesis genes: retinol dehydrogenase 5 (RDH5) and retinol dehydrogenase L (RDHL) in colon adenomas and carcinomas as compared with normal colon. Consistent with the adenoma and carcinomas samples, seven colon carcinoma cell lines also lacked expression of RDH5 and RDHL. Assessment of RDH enzymatic activity within these seven cell lines showed poor conversion of retinol into retinoic acid when compared with normal cells such as normal human mammary epithelial cells. Reintroduction of wild type APC into an APC-deficient colon carcinoma cell line (HT29) resulted in increased expression of RDHL without affecting RDH5. APC-mediated induction of RDHL was paralleled by increased production of retinoic acid. Investigations into the mechanism responsible for APC induction of RDHL indicated that beta-catenin fails to repress RDHL. The colon-specific transcription factor CDX2, however, activated an RDHL promoter construct and induced endogenous RDHL. Finally, the induction of RDHL by APC appears dependent on the presence of CDX2. We propose a novel role for APC and CDX2 in controlling retinoic acid biosynthesis and in promoting a retinoid-induced program of colonocyte differentiation.
...
PMID:The tumor suppressor adenomatous polyposis coli and caudal related homeodomain protein regulate expression of retinol dehydrogenase L. 1519 67

There is substantial overlap in retinol and alcohol metabolism. Mice that lack retinoic acid (RA) receptor retinoid X receptor alpha (RXRalpha) expression in the liver are more susceptible to alcoholic liver disease. To investigate the interaction between RXRalpha and alcoholic liver disease, ethanol metabolism was studied in hepatocyte RXRalpha-deficient [RXRalpha knockout (KO)] mice. Hepatocyte RXRalpha deficiency resulted in a significant increase in hepatic alcohol dehydrogenase (ADH) activity, ADH1 protein, but not Adh1 mRNA. Polysomal distribution analysis indicated that more polysome-associated Adh1 mRNA was present in the mutant mouse livers, suggesting increased ADH1 protein synthesis in RXRalpha KO mice compared with wild-type mice. However, ADH2 and ADH3 enzyme activities were not affected by RXRalpha deficiency. Although ethanol clearance was increased, acetaldehyde elimination was reduced when RXRalpha was not expressed in the liver. Both mitochondrial aldehyde dehydrogenase (ALDH) 2 and cytosolic ALDH activities were reduced in the mutant mice compared with the wild type. Western blot analysis revealed that the levels of ALDH1A1 and ALDH1A2 were decreased in the mutant mice. Semiquantitative reverse transcriptase-polymerase chain reaction indicated that liver Aldh1a1 mRNA level was also reduced due to the lack of RXRalpha expression. Thus, RXRalpha differentially affects ADH and ALDH activity, leading to an increase in alcohol clearance, but a reduction in acetaldehyde elimination. In addition, CYP2E1 as well as mitochondrial and cytosolic glutathione S-transferase activities were significantly lower in RXRalpha KO mice than in wild-type mice. Our results reveal the central role of RXRalpha in ethanol metabolism.
...
PMID:The role of retinoid X receptor alpha in regulating alcohol metabolism. 1682 25

Human endometrium undergoes modifications in preparation for embryonic implantation. This study investigated in vivo the endocrine effects of pregnancy on the endometrium, using the model of ectopic pregnancy. Endometrial biopsies from 9 subjects with ectopic pregnancy (Preg) were compared with 8 and 6 samples of mid and late secretory endometrium, respectively. After hybridizing with Affymetrix HGU133 Plus 2 chips, data were analyzed using GeneSpring GX and Ingenuity Pathways Analysis. From 54,675 genes, 3021 genes were significantly differentiated when mid-secretory endometrium was compared with the Preg (Volcano plot; P < .05, >or=2-fold change).The complement and coagulation cascade, phospholid degradation, glycosphingolipid biosynthesis (globoseries), retinol metabolism, antigen presentation pathway, glycosphingolipid biosynthesis, and O-glycan biosynthesis were main significant canonical pathways found in Preg samples. Validation was done with reverse transcriptase polymerase chain reaction. In conclusion, the ectopic embryo has a significant impact, by an endocrine mechanism, on endometrium, when compared with the window of implantation.
...
PMID:Endometrial gene expression in early pregnancy: lessons from human ectopic pregnancy. 1859 49

Retinoids play important roles in many diverse biological functions such as cell growth, morphogenesis, differentiation, and reproduction. Previous studies demonstrated that retinol administration to ewes, followed by natural service, resulted in embryos with improved competence to develop under standard in vitro conditions (5% CO(2) in air). Additional studies provided evidence that retinol may have some antioxidant effect by improving blastocyst development in cattle under atmospheric conditions (5% CO(2) in air). Glutathione is an important non-protein, sulphydryl compound found in oocytes and embryos, which acts to decrease oxidative stress. The purpose of the present study was to evaluate the effects of retinol administration to ewes on the content of glutathione and glutathione-related and antioxidant enzymes in in vivo matured sheep oocytes. Briefly, ewes were administered retinol or vehicle during superovulation, and after 60h the oviducts were removed and mature oocytes collected. Glutathione content did not differ significantly between oocytes collected from retinol-treated ewes (6.78+/-3.81pmol/oocyte) and control ewes (6.38+/-1.58pmol/oocyte). Transcripts encoding for manganese superoxide dismutase (Mn-SOD), copper zinc superoxide dismutase (Cu-Zn SOD), glutathione synthetase (GS), and glutathione transferase pi (GSTp) were detected in single ovine oocytes; however, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not reveal any significant differences in transcripts between oocytes from retinol-treated ewes and those from control ewes.
...
PMID:Glutathione content and antioxidant enzyme expression of in vivo matured sheep oocytes. 1927 97


1 2 Next >>

---