Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has previously been reported that retinaldehyde can be converted to retinoic acid by cytosolic aldehyde dehydrogenase (AHD-2) in liver extracts [Biochem. Pharmacol. 42: 1279-1285 (1991)]. To determine which enzyme(s) carried out this reaction in murine embryonic stem cells, two aldehyde dehydrogenases were cloned; the AHD-2 gene was cloned from a liver cDNA library, and a closely related gene, AHD-M1, was cloned from an embryonic F9 cell cDNA library by conserved oligonucleotide sequence screening. AHD-M1 contained an open reading frame of 1554 base pairs, which encoded 517 amino acids. The AHD-M1 gene encoded a protein with a putative amino acid sequence that was 94% and 97% identical to the mitochondrial aldehyde dehydrogenases of human and rat, respectively, and thus we have cloned the murine cDNA for this enzyme for the first time. The AHD-M1 cDNA was only 64% identical to AHD-2. Northern analysis showed that AHD-M1 mRNA was constitutively expressed in F9 and P19 embryonic teratocarcinoma stem cells and in AB1 embryonic stem cells. There was a 3-5-fold retinoic acid-associated increase in the amount of this mRNA during the differentiation of F9 cells into parietal endoderm. In contrast, we could not detect the expression of AHD-2 mRNA in AB1, P19, or F9 cells, even though the F9 cells could convert retinaldehyde to retinoic acid. When the AHD-M1 and AHD-2 cDNAs were inserted into the expression vector pSG5 and transfected into cultured COS cells, 3-5-fold and 100-fold increases, respectively, in the conversion of [3H]retinaldehyde to [3H]retinoic acid could be detected by high performance liquid chromatographic assay. We conclude that both enzymes are capable of converting retinaldehyde to retinoic acid in intact COS cells. AHD-2 is more active than AHD-M1 in this conversion, but AHD-2 is not the enzyme responsible for this conversion in F9 embryonic stem cells.
Mol Pharmacol 1994 Jul
PMID:Enzymatic conversion of retinaldehyde to retinoic acid by cloned murine cytosolic and mitochondrial aldehyde dehydrogenases. 805 62

Gangliosides are known to be suitable targets for immune attack against cancer but they are poorly immunogenic. Active immunization with ganglioside/BCG or liposome vaccines results in moderate titer IgM antibody responses of short duration. Covalent attachment of poorly immunogenic antigens to immunogenic proteins is a potent method for inducing an IgG antibody response. GD3, a dominant ganglioside on malignant melanoma, was modified by ozone cleavage of the double bond in the ceramide backbone, an aldehyde group introduced and used for coupling via reductive amination to epsilon-amino-lysyl groups of proteins. Utilizing this method, GD3 conjugates were constructed with: 1. Synthetic multiple antigenic peptide (MAP) constructs expressing 4 repeats of a malaria T-cell epitope; 2. Outer membrane proteins (OMP) of Neisseria meningitidis; 3. Cationized bovine serum albumin; 4. Keyhole limpet hemocyanin (KLH); and 5. Polylysine. In addition, conjugates containing only the GD3 oligosaccharide were synthesized. All constructs were tested for antigenicity using anti-GD3 antibody R24, and for immunogenicity in mice. Serum antibody levels were analyzed by ELISA and immune thin-layer chromatography. Results in the mouse show a significant improvement in the IgM antibody response and a consistent IgG response against GD3 using GD3-KLH conjugates. Other carrier proteins and the use of GD3 oligosaccharide were significantly less effective. If improved immunogenicity and clinical benefit with conjugate vaccines can be demonstrated in patients with melanoma, this approach may be applicable to patients with other tumors of neuroectodermal origin, including gliomas, glioblastomas, astrocytomas, and neuroblastomas.
Mol Chem Neuropathol
PMID:Ganglioside conjugate vaccines. Immunotherapy against tumors of neuroectodermal origin. 808 40

Acrolein, a highly cytotoxic aldehyde, is a metabolic by-product of the antineoplastic agent cyclophosphamide and is responsible for the development of hemorrhagic cystitis, a serious side effect of cyclophosphamide therapy. Aldose reductase (EC 1.1.1.21), a member of the aldo-keto reductase superfamily, catalyzes the NADPH-dependent reduction of acrolein to allyl alcohol (Km = 80 microM, kcat = 87 min-1). Aldose reductase is expressed at different levels in individuals. This suggests that individual differences in the reductive metabolism of acrolein may be a determinant of acrolein toxicity. In addition to being a substrate, acrolein also produces a time-dependent 7-20-fold increase in the activity of aldose reductase toward a variety of substrates. This involves initial binding of acrolein to a second site (Ks = 58 microM). Acrolein activation of aldose reductase results not only in higher kcat values for all substrates but also in higher Km values and decreased catalytic efficiencies. Acrolein activation of aldose reductase reduces its affinity for aldose reductase inhibitors.
Mol Pharmacol 1994 Apr
PMID:Aldose reductase-catalyzed reduction of acrolein: implications in cyclophosphamide toxicity. 818 57

The major nonpolar iodolipid formed in horse thyroid cells has recently been identified as 2-iodohexadecanal (2-IHDA). We have investigated in vitro the effect of 2-IHDA on the NADPH-oxidase, NADPH-cytochrome c reductase, and thyroid peroxidase (TPO) activities of a porcine thyroid plasma membrane preparation. 2-IHDA inhibited NADPH-oxidase activity, with half-inhibition at 3-5 microM, but it had no effect on NADPH-cytochrome c reductase. It inhibited the TPO-catalyzed iodination of protein, but not iodide oxidation. Hexadecanal also inhibited NADPH-oxidase. Inhibition by the non-iodinated lipid aldehydes depended on the length of their aliphatic chain: dodecanal and tridecanal gave maximal inhibition. Free iodide, 2-iodohexadecanol and palmitic acid all had no inhibitory effect. Washing treated membranes showed that the inhibition of NADPH-oxidase by hexadecanal was fully reversible, whereas that of 2-IHDA and other iodinated or brominated alkanals was irreversible. Thus the interaction between some residues of the thyroid NADPH-oxidase and the lipid aldehyde groups was favored or stabilized by the iodine atom. Modification of primary amine and thiol groups of NADPH-oxidase inhibited its activity. These groups could also be the target of lipid aldehydes. We suggest that 2-IHDA, because it inhibits TPO and more profoundly the H2O2-generating system in thyroid plasma membrane, modulates iodide metabolism in the thyrocyte and may mediate the Wolff-Chaikoff effect.
Mol Cell Endocrinol 1994 Feb
PMID:Inhibition of thyroid NADPH-oxidase by 2-iodohexadecanal in a cell-free system. 818 56

When inhaled, ozone reacts at the airway luminal surface with unsaturated fatty acids contained in the extracellular fluid and plasma membrane to form an aldehyde and hydroxyhydroperoxide. The resulting hydroxyhydroperoxide degrades in aqueous systems to yield a second aldehyde and hydrogen peroxide (H2O2). Previously, we demonstrated that ozone can augment eicosanoid metabolism in bovine airway epithelial cells. To examine structure-activity relationships of ozone-fatty acid degradation products on eicosanoid metabolism in human airway epithelial cells, 3-, 6-, and 9-carbon saturated aldehydes and hydroxyhydroperoxides were synthesized and purified. Eicosanoid metabolism was evaluated by determination of total 3H-activity release from confluent cells previously incubated with [3H]arachidonic acid and by identification of specific metabolites with high performance liquid chromatography and radioimmunoassay. The major metabolites detected were prostaglandin E2, prostaglandin F2 alpha, and 15-hydroxyeicosatetraenoic acid. The 9-carbon aldehyde, nonanal, in contrast to 3- or 6-carbon aldehydes, stimulated release at concentrations > or = 100 microM, suggesting that the stimulatory effect increases with increasing chain length. When tested under identical conditions, the 3-, 6-, and 9-carbon hydroxyhydroperoxides were more potent than the corresponding aldehydes. Again, a greater effect was noted when the chain length was increased. One possible explanation for the increased potency of the hydroxyhydroperoxides over the aldehydes could be due to degradation of the hydroxyhydroperoxide into H2O2 and aldehyde. We consider this an unlikely explanation because responses varied with chain length (although each hydroxyhydroperoxide would produce an equivalent amount of H2O2) and because exposure to H2O2 alone or H2O2 plus hexanal produced a response dissimilar to 1-hydroxy-1-hexanehydroperoxide.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Dec
PMID:Ozonolysis products of membrane fatty acids activate eicosanoid metabolism in human airway epithelial cells. 825 91

4-Hydroxynonenal (HNE), a major lipid peroxidation product, displays several biological actions. Among them, the differentiation of human HL-60 cells and the stimulation of neutrophil oriented migration occur at concentrations which can be actually found in normal tissues and in body fluids. In spite of its chemotactic activity, HNE fails to increase neutrophil oxidative metabolism. The action of the aldehyde on cell migration appears to be mediated by a phosphoinositide specific phospholipase C. The acceleration of phosphatidylinositol turnover induced by 10 pM 4-hydroxyoctenal, another lipid peroxidation product, is prevented by the pretreatment of neutrophils with pertussis toxin. The mechanism of action of these 4-hydroxyalkenals appears to follow pathways common to other chemoattractants, but some differences can be found too. In particular HNE seems unable to stimulate phospholipase D activity. The action of 4-hydroxyalkenals and other lipid peroxidation products on transmembrane signalling systems and on phospholipid metabolism might regulate several cell functions, such as motility, proliferation and differentiation.
Mol Aspects Med 1993
PMID:Action of lipid peroxidation products on phosphoinositide specific phospholipase C. 826 43

The effects of acute ethanol intoxication on the glycoprotein metabolism of rat liver Golgi apparatus have been investigated. A marked reduction of the galactosyltransferase and sialyltransferase activities was observed in Golgi membranes 6 h after ethanol administration (6g/Kg body wt) together with the retention of glycoproteins in the hepatocyte. Methylpyrazole, an inhibitor of alcohol dehydrogenase, administrated "in vivo" (10 mg/Kg body wt) prevented the ethanol-induced inhibition of both the transferase activities. Acetaldehyde formed "in vitro" unstable and stable adducts with Golgi membrane proteins and with purified galactosyltransferase. These results suggest that the impairment of glycoprotein metabolism at the level of liver Golgi apparatus may be mediated, at least in part, through the acetaldehyde formation during ethanol oxidation.
Biochem Mol Biol Int 1993 Apr
PMID:Acetaldehyde-induced impairment of protein glycosylation in liver Golgi apparatus. 833 19

Human and Bovine kidney aldose and aldehyde reductases from cortex, medulla and papilla have been purified by DE-52 column chromatography or chromatofocusing and have been biochemically characterized. In both human and bovine kidney, cortex contains only aldehyde reductase and papilla aldose reductase. Medulla however, contains aldose as well as aldehyde reductase.
Biochem Mol Biol Int 1993 May
PMID:The distribution of aldose and aldehyde reductases in different regions of human and bovine kidney. 835 34

Murine corneal aldehyde dehydrogenase has been purified to homogeneity and characterized with a range of aldehyde substrates at pH 7.4. The enzyme was a dimer with a subunit molecular weight of 59 KDa. and appears to prefer aldehyde products of lipid peroxidation as substrates. The enzyme constituted approximately 5% of the total soluble protein of mouse cornea. A dual role has been proposed for corneal aldehyde dehydrogenase in providing the eye with protection against UV-B light: by oxidizing aldehydes generated through light-induced lipid peroxidation; and by the direct absorption of UV-B light by the enzyme.
Biochem Mol Biol Int 1993 Jul
PMID:Purification and properties of murine corneal aldehyde dehydrogenase. 840 11

We tested six additional chemicals (acetaldehyde, benomyl, diethylstilboestrol, diethylstilboestrol dipropionate, griseofulvin, and mercaptoethanol) for in vitro systems of the coordinated programme to study aneuploidy induction sponsored by the Commission of the European Communities in two in vitro test systems. Using Saccharomyces cerevisiae D61.M (mitotic chromosomal malsegregation assay), benomyl showed a dose-dependent increase in the frequency of chromosomal malsegregation with a lowest effective dose tested (LEDT) of 30 micrograms/ml (0.1 mM). Diethylstilboestrol (DES) showed solvent-dependent effects. DES dissolved in ethanol induced an increase in chromosomal malsegregation as well as in the frequency of total resistant colonies (mutations and recombinations) with a LEDT around 13 micrograms/ml (0.048 mM). Using dimethylsulfoxide as the solvent, no increases were observed with DES up to 333 micrograms/ml (1.24 mM). Acetaldehyde induced an increase in chromosomal malsegregation with the cold treatment protocol (LEDT: 1.25 microliters/ml (21 mM) and 0.75 microliters/ml (13 mM), respectively) but no increase with the overnight protocol (highest dose tested (HDT): 1.75 microliters/ml; 30 mM). Concerning the frequency of total cycloheximide-resistant colonies (mutations and recombinations) increases were obtained with both protocols. The other three compounds were negative when tested up to toxic doses (survival below 10%), up to the maximum solubility in the solvent used or up to heavy precipitation in the incubation mix. The HDT were 333 micrograms/ml (0.88 mM) for diethylstilboestrol dipropionate, 1,600 micrograms/ml (4.5 mM) for griseofulvin and 0.5 microliters/ml (7 mM) for mercaptoethanol. Concerning effects on porcine brain tubulin assembly in vitro, diethylstilboestrol and griseofulvin inhibited the assembly process. The IC30% (30% inhibition concentration) values were 12.5 microM and 100 microM for DES and griseofulvin, respectively. Mercaptoethanol showed no effects up to 50 mM.
Environ Mol Mutagen 1993
PMID:Analysis of the six additional chemicals for in vitro assays of the European Economic Communities' EEC aneuploidy programme using Saccharomyces cerevisiae D61.M and the in vitro porcine brain tubulin assembly assay. 844 45


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