Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A series of aldehyde dehydrogenase isozymes (aldehyde:NAD (P)+ oxidoreductase, EC 1.2.1.5), has been purified from hepatomas induced in Sprague-Dawley rats by 2-acetylaminofluorene. 2. The functional hepatoma-specific aldehyde dehydrogenase isozymes exist as 105 000-dalton dimers composed to two subunits of 53 000 daltons. Isoelectric points of the purified isozymes are 6.9-7.2. 3. Antiserum to these purified hepatoma-specific aldehyde dehydrogenases has been produced and the immunological relationships of these isozymes to their normal liver counterpart have been studied. Results of Ouchterlony double diffusions, agar-gel immunoelectrophoresis and polyacrylamide gel and agar immunoelectrophoresis indicate that anti-hepatoma aldehyde dehydrogenase antiserum cross-reacts with normal liver aldehyde dehydrogenase.
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PMID:Purification and immunochemical characterization of aldehyde dehydrogenase from 2-acetylaminofluorene-induced rat hepatomas. 18 64

The pre- and post-natal ontogeny of Sprague-Dawley rat liver aldehyde dehydrogenase [aldehyde-NAD(P)(+) oxidoreductase, EC 1.2.1.5] is described. At no time in its ontogenetic development does normal liver aldehyde dehydrogenase exhibit any of the characteristics of a series of unique aldehyde dehydrogenases that can be isolated from 2-acetamidofluorene-induced rat hepatomas. Enzyme activity is first detectable in 15-day foetal liver and gradually increases throughout pre- and post-natal development until adult activities are attained by day 49 after birth. Electrophoretically, normal aldehyde dehydrogenase, throughout its ontogeny, exists as the same single isoenzyme found in normal adult liver. Isoelectric points for two normal liver isoenzymes demonstrable by isoelectric focusing are pH5.9 and 6.0. The immunochemical properties of aldehyde dehydrogenase during its ontogeny are identical with those of normal adult liver aldehyde dehydrogenase when tested against anti-(hepatoma aldehyde dehydrogenase) serum in Ouchterlony double-diffusion tests. The results indicate that the hepatoma-specific aldehyde dehydrogenases are not the result of the de-repression of genes normally repressed in adult rat liver or in some other adult tissue.
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PMID:Aldehyde dehydrogenase in 2-acetamidofluorene-induced rat hepatomas. Ontogeny and evidence that the new isoenzymes are not due to normal gene de-repression. 19 78

The antitumor activity of 2,3-dihydroxybutyraldehyde on Ehrlich carcinoma, Sarcoma 180, and Yoshida AH 130 hepatoma, as well as the aldehyde dehydrogenase activity in these tumors, was studied. 2,3-Dihydroxybutyraldehyde at nontoxic doses (500 mg/kg body weight i.p. daily for 7 days) slowed down the growth of solid and ascites tumors in mice. The treatment completely prevented the development of Yoshida ascites hepatoma in several rats. 2,3-Dihydroxybutyraldehyde, although it did not influence the growth of Ehrlich carcinoma transplanted in the brain of mice, significantly decreased in the lungs of these animals the number of viable tumour cells that derived from the primary tumor. All the tested tumors, which were sensitive to the action of 2,3-dihydroxybutyraldehyde, were virtually devoid of aldehyde dehydrogenase activity. These results suggest a possible relationship between the lack of this enzyme activity and the antitumor activity of aliphatic aldehydes.
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PMID:Carcinostatic effect of aliphatic aldehydes and aldehyde dehydrogenase activity in Ehrlich carcinoma, Sarcoma 180, and Yoshida AH 130 hepatoma. 20 25

The subcellular distribution and properties of four aldehyde dehydrogenase isoenzymes (I-IV) identified in 2-acetylaminofluorene-induced rat hepatomas and three aldehyde dehydrogenases (I-III) identified in normal rat liver are compared. In normal liver, mitochondria (50%) and microsomal fraction (27%) possess the majority of the aldehyde dehydrogenase, with cytosol possessing little, if any, activity. Isoenzymes I-III can be identified in both fractions and differ from each other on the basis of substrate and coenzyme specificity, substrate K(m), inhibition by disulfiram and anti-(hepatoma aldehyde dehydrogenase) sera, and/or isoelectric point. Hepatomas possess considerable cytosolic aldehyde dehydrogenase (20%), in addition to mitochondrial (23%) and microsomal (35%) activity. Although isoenzymes I-III are present in tumour mitochondrial and microsomal fractions, little isoenzyme I or II is found in cytosol. Of hepatoma cytosolic aldehyde dehydrogenase activity, 50% is a hepatoma-specific isoenzyme (IV), differing in several properties from isoenzymes I-III; the remainder of the tumour cytosolic activity is due to isoenzyme III (48%). The data indicate that the tumour-specific aldehyde dehydrogenase phenotype is explainable by qualitative and quantitative changes involving primarily cytosolic and microsomal aldehyde dehydrogenase. The qualitative change requires the derepression of a gene for an aldehyde dehydrogenase expressed in normal liver only after exposure to potentially harmful xenobiotics. The quantitative change involves both an increase in activity and a change in subcellular location of a basal normal-liver aldehyde dehydrogenase isoenzyme.
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PMID:Subcellular distribution and properties of aldehyde dehydrogenase from 2-acetylaminofluorene-induced rat hepatomas. 53 88

The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces the expression of a number of genes. The biochemical process of the induction of aldehyde dehydrogenase (ALDH-3) was investigated in rat H4IIE hepatoma cells in culture. The kinetics of ALDH-3-induction exhibited parallel increases in the rate of transcription, mRNA, protein, and enzyme activity, all reaching a plateau at 36-48 h after addition of TCDD. Half maximal and maximal inductions occurred at 0.1 and 1 nM of TCDD, respectively. No significant changes in the half-life of ALDH-3 mRNA (14 h) were observed in the cells exposed to three different concentrations of TCDD. Other inducers of xenobiotic metabolism, such as 3-methylcholanthrene and beta-naphthoflavone, also induced ALDH-3 mRNA to a similar level as TCDD, whereas antioxidants or electrophiles, such as tert-butylhydroquinone and dimethyl fumarate, did not show any induction of ALDH-3 mRNA. To examine the involvement of the aryl hydrocarbon receptor (Ah receptor) in the induction of ALDH-3, mouse variant cell lines defective in cytochrome P450IA1-induction and a parental wild type cell line (Hepa1c1c7) were studied. ALDH-3 mRNA and the transcription of its gene were detected in TCDD-treated wild type cells, but not in the treated and untreated variant cells. These results demonstrate that TCDD induces transcription of the ALDH-3 gene via its binding to the Ah receptor.
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PMID:Regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible expression of aldehyde dehydrogenase in hepatoma cells. 141 78

The mouse hepatoma cell line Hepa-1 was shown to express an aldehyde dehydrogenase (ALDH) isozyme which was inducible by TCDD and carcinogenic polycyclic aromatic hydrocarbons. The induced activity could be detected with benzaldehyde as substrate and NADP as cofactor (B/NADP ALDH). As compared with rat liver and hepatoma cell lines, the response was moderate (maximally 5-fold). There was an apparent correlation between this specific form of ALDH and aryl hydrocarbon hydroxylase (AHH) in the Hepa-1 wild-type cell line--in terms of inducibility by several chemicals. However, the magnitude of the response was clearly smaller for ALDH than for AHH. Southern blot analysis showed that a homologous gene (class 3 ALDH) was present in the rat and mouse genome. The gene was also expressed in Hepa-1 and there was a good correlation between the increase of class 3 ALDH-specific mRNA and B/NADP ALDH enzyme activity after exposure of the Hepa-1 cells to TCDD. It is concluded that class 3 ALDH is inducible by certain chemicals in the mouse hepatoma cell line, although the respective enzyme is not inducible in mouse liver in vivo.
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PMID:Induction of class 3 aldehyde dehydrogenase in the mouse hepatoma cell line Hepa-1 by various chemicals. 150 55

We have examined enzyme activities and mRNA levels corresponding to aldehyde dehydrogenase-3 genes encoding cytosolic (ALDH3c) and microsomal (ALDH3m) forms. In contrast to negligible activities in the intact mouse liver, both ALDH3c and ALDH3m enzyme activities are inducible by benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mouse hepatoma Hepa-1c1c7 cell cultures. Constitutive mRNA levels of ALDH3c are virtually absent, whereas those of ALDH3m are substantial; using Hepa-1 mutant lines, we show that both ALDH3c and ALDH3m are TCDD-inducible by an Ah receptor-dependent mechanism. Basal mRNA levels of ALDH3c, but not those of ALDH3m, are strikingly elevated in untreated mutant cells lacking a functional CYP1A1 enzyme; low ALDH3c basal mRNA levels can be restored by introduction of a functional murine CYP1A1 or human CYP1A2 enzyme into these mutant cells. These data suggest that the TCDD induction process is distinct from the CYP1A1/CYP1A2 metabolism-dependent repression of constitutive gene expression; we suggest that this latter property classifies the Aldh-3c gene, but not the Aldh-3m gene, as a member of the murine [Ah] battery.
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PMID:Negative regulation of the murine cytosolic aldehyde dehydrogenase-3 (Aldh-3c) gene by functional CYP1A1 and CYP1A2 proteins. 152 Mar 28

The NAD- and NADP-dependent aldehyde dehydrogenase (ALDH) activities were evaluated in two rat hepatoma cell lines, namely the well-differentiated MH1C1 line and the less differentiated HTC line. Each activity was determined in parallel in isolated rat hepatocytes, for comparison. The aliphatic aldehyde acetaldehyde (ACA) and the aromatic aldehyde benzaldehyde (BA) were used as substrates. With the first substrate the ALDH activities found in the crude cytoplasmic extracts were lower in hepatoma cells than in normal hepatocytes, especially when measured with NADP as coenzyme (ACA/NADP). Otherwise, with benzaldehyde as substrate the NAD-dependent enzyme activity (BA/NAD) was increased about 9-fold in HTC cells over hepatocytes and decreased in MH1C1 cells, while the NADP-dependent (BA/NADP) activity was increased 38- and 2.5-fold in HTC and MH1C1 cell lines, respectively. Studies on the subcellular distribution of these enzyme activities showed that the activity measured with acetaldehyde and NAD (ACA/NAD) was almost equally distributed between the cytosol and the subcellular particles in the three cell populations, but the ACA/NADP activity was shifted towards the cytosolic compartment in hepatomas, especially in HTC cells. The BA/NAD and BA/NADP ALDH activities found in the organelles of hepatoma cells were markedly reduced in comparison with hepatocytes, in favour of the cytosol. The most striking difference between the normal and the transformed cells was the 94-fold increase over hepatocytes of the BA/NADP activity, found in the cytosolic fractions of HTC cells. MH1C1 cells showed a less pronounced (7.5-fold) enhancement of this tumour-associated specific activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative subcellular distribution of benzaldehyde and acetaldehyde dehydrogenase activities in two hepatoma cell lines and in normal hepatocytes. 166 Dec 6

An aldehyde dehydrogenase isozyme, ALDH3, which is strongly expressed in the stomach, may play a role in the oxidation of toxic aldehydes. Using reverse genetic approach, we cloned and characterized the cDNA and the gene for the ALDH3. The full length cDNA is 1624 base pairs (bp) in length and contains an open reading frame encoding 453 amino acid residues. The deduced amino acid sequence shows a high degree of resemblance to that of rat hepatocarcinoma ALDH. The human ALDH3 gene spans about 8 kb in length and consists of 10 exons. The putative TATA and CCAAT boxes are located in the consensus upstream distance from the transcription initiation site. Southern blot analysis of total genomic DNA argues against the proposed two-gene model for the ALDH3 isozymes (Yin, S.-J., Cheng, T.-C., Chang, C.-P., Chen, Y.-J., Chao, Y.-C., Tang, H.-S., Chang, T.-M., and Wu, C.-W. (1988) Biochem. Genet. 26, 343-360). Northern blot hybridization and analysis of PCR amplification products of cellular RNA demonstrated the existence of a high level of ALDH3 mRNA in human stomach and hepatoma cells, but a very low level in the normal liver. Expression of ALDH3 cDNA in Escherichia coli yielded a protein of 55 kDa, which exhibited kinetic properties similar to that found in ALDH3 isozyme purified from human stomach and liver, and was hybridizable with rabbit anti-human-hepatoma ALDH serum.
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PMID:Human stomach aldehyde dehydrogenase cDNA and genomic cloning, primary structure, and expression in Escherichia coli. 173 58

We have isolated and characterized cDNA clones encoding rat liver cytosol 10-formyltetrahydrofolate dehydrogenase (EC 1.5.1.6). An open reading frame of 2706 base pairs encodes for 902 amino acids of Mr 99,015. The deduced amino acid sequence contains exact matches to the NH2-terminal sequence (28 residues) and the sequences of five peptides derived from cyanogen bromide cleavage of the purified protein. The amino acid sequence of 10-formyltetrahydrofolate dehydrogenase has three putative domains. The NH2-terminal sequence (residues 1-203) is 24-30% identical to phosphoribosylglycinamide formyltransferase (EC 2.1.2.2) from Bacillus subtilis (30%), Escherichia coli (24%), Drosophila melanogaster (24%), and human hepatoma HepG2 (27%). Residues 204-416 show no extensive homology to any known protein sequence. Sequence 417-900 is 46% (mean) identical to the sequences of a series of aldehyde dehydrogenase (NADP+) (EC 1.2.1.3). Intact 10-formyltetrahydrofolate dehydrogenase exhibits NADP-dependent aldehyde dehydrogenase activity. The sequence identity to phosphoribosylglycinamide formyltransferase is discussed, and a binding region for 10-formyltetrahydrofolate is proposed.
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PMID:Isolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase. 184 31


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