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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the current theories of cardiovascular disease is that it may begin with oxygen radical-induced damages. Extensive studies have been made in different laboratories to elucidate the mechanism of oxidative damages in the presence of added iron salts. However, those in vitro studies are unlikely to be relevant to the in vivo situation, where in the normal physiological condition most of the iron remains bound with proteins. In the present study we have demonstrated that an in vitro system containing desferrioxamine, a strong iron chelator, superoxide generated by the action of xanthine oxidase on acetaldehyde initiates lipid peroxidation and protein changes in the guinea pig cardiac microsomes. We have further demonstrated that superoxide-initiated lipid peroxidation and protein changes are completely prevented by ascorbic acid. SOD also prevents but catalase, alpha-tocopherol, glutathione, uric acid, thiourea, mannitol and histidine are without effect. When NADPH is used instead of generated superoxide, the lipid peroxidation and protein changes are exclusively inhibited by ascorbic acid. SOD, catalase and other antioxidants are ineffective. The results obtained with guinea pigs may be extrapolated to humans, because like guinea pigs humans are also incapable of synthesizing ascorbic acid.
Mol Cell Biochem 1993 Sep 08
PMID:Protective effect of ascorbic acid against lipid peroxidation and oxidative damage in cardiac microsomes. 810 91

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

The subcellular localization of the aldehyde dehydrogenase activity from the ALDH (EC 1.2.1.3) enzyme has been studied in nutritionally manipulated Drosophila melanogaster adults from a wild (LRC) and an ADH-null (bAdhn4) strain. ALDH activities from ALDH or ADH (EC 1.1.1.1) enzymes were selectively inhibited by prefeeding respectively the flies sucrose solutions supplemented with either cyanamide or acetone respectively. ALDH, ADH (as a cytosolic marker) and succinate dehydrogenase (EC 1.3.9.1) (as a mitochondrial marker) activities were assayed in both the mitochondrial and cytosolic fractions isolated from flies subjected to each treatment. Total ALDH activity in the cytosolic fraction was found to be between five (ADH strain) and ten (ADH strain) times higher than that in the mitochondrial fraction. Prefeeding cyanamide resulted in a 64% (ADH strain) and a 90% (ADH strain) reduction of the cytosolic ALDH activity, whereas prefeeding acetone resulted in a 38% (ADH strain) reduction of this activity. Prefeeding both cyanamide and acetone resulted in a total inhibition of ALDH activity, which was also observed after an extended cyanamide treatment. In conclusion, our results support that, contrary to what occurs in larvae, in adults the ALDH activity from ALDH enzyme is mainly localized in the cytosolic fraction: about 85% in ADH+ and 90% in ADH- strains. Although larvae and adults use different ALDH activities to detoxify acetaldehyde (from ADH and ALDH enzymes, respectively) both of them are cytosolic. Reasons for these different uses are discussed in relation to the subcellular localization of ALDH activity.
Insect Biochem Mol Biol 1993 Jul
PMID:Aldehyde dehydrogenase (ALDH) activity in Drosophila melanogaster adults: evidence for cytosolic localization. 835 17

Ethanol is known to acutely inhibit glucose-stimulated glycogen deposition in skeletal muscles in the rat. This effect is selective for oxidative as opposed to non-oxidative muscles. This paper explores the biochemical basis for this selective impairment in muscle glycogen metabolism. 4-Methylpyrazole, a potent inhibitor of alcohol dehydrogenase, potentiated the ethanol-mediated impairment in glycogen deposition in oxidative muscles and was associated with abnormalities in glycogen deposition in non-oxidative muscles. By contrast, disulfiram, a potent inhibitor of aldehyde dehydrogenase had no effect on the ethanol-mediated impairment in glycogen deposition in both oxidative and non-oxidative muscles. The implication is that it is the ethanol molecule itself, and not one of its metabolites (acetaldehyde, acetate, excess NADH), that mediates the defect in glycogen metabolism.
Biochem Mol Biol Int 1993 May
PMID:The mechanism(s) of the alcohol-induced impairment in glycogen synthesis in oxidative skeletal muscles. 835 29

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


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