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)

Abetalipoproteinemia is an inherited disorder of lipoprotein metabolism. Affected individuals produce virtually no circulating apolipoprotein B-containing lipoproteins (chylomicrons, very low density lipoprotein, low density lipoprotein and lipoprotein (a)). Malabsorption of the antioxidant vitamin E occurs, leading to spinocerebellar and retinal degeneration. Biochemical and genetic studies show that abetalipoproteinemia is not a defect of lipid biosynthesis or of the apolipoprotein B gene. Instead a microsomal triglyceride transfer protein, which exists as a complex with protein disulphide isomerase in the endoplasmic reticulum, has been implicated. We have cloned and sequenced the human cDNA encoding microsomal triglyceride transfer protein. The predicted amino acid sequence shows extensive homology to vitellogenin, the precursor of the lipovitellin complex, which has been shown by X-ray crystallography to contain a large lipid storage cavity. Microsomal triglyceride transfer protein is expressed in ovary, testis and kidney, in addition to liver and small intestine. A homozygous mutation that disrupts splicing has been identified in affected siblings with classical abetalipoproteinemia. These results elucidate a key process in the packaging of apolipoprotein B with lipid, and should increase our understanding of the processes regulating the production of atherogenic lipoproteins.
Hum Mol Genet 1993 Dec
PMID:Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein. 811 81

Laser Doppler Electrophoresis was used to detect changes in the surface charge of low density lipoprotein populations exposed to oxidative stress. Before oxidative stress, low density lipoprotein suspensions exhibited homogenous populations of net negative charge but after exposure to hydroxyl and superoxide radicals, peroxyl radicals, or by Cu2+ generated oxidants they exhibited Laser Doppler Electrophoresis changes. The major population of low density lipoprotein became more negatively charged, in agreement with agarose gel electrophoresis. However, Laser Doppler Electrophoresis detected greater heterogeneity of low density lipoprotein, compared to agarose gel electrophoresis. Partially oxidized low density lipoprotein exhibited a less negatively charged subpopulation of particles compared to control samples. This has not been reported previously. Hence, Laser Doppler Electrophoresis is a sensitive method for detecting the appearance of subpopulations of differing surface charge density in oxidatively modified low density lipoprotein. beta-carotene protected low density lipoprotein against oxidative modification even when endogenous vitamin E levels are low. Vitamin E-deficient low density lipoprotein pretreated with beta-carotene exhibited a more narrow negative population when oxidized with peroxyl radicals, compared to control. Native low density lipoprotein pretreated with a mixture of all-trans- and cis-beta-carotene was also protected.
Biochem Mol Biol Int 1993 Aug
PMID:Electrophoretic mobility changes of oxidized human low density lipoprotein measured by laser Doppler electrophoresis. 822 Feb 56

We have previously demonstrated fucosyltransferase (FT) activity on mouse germ cell surfaces at different stages of spermatogenesis. To complement these findings, here we report FT activity on the Sertoli cell (SC) surface. SC isolated and cultured from 20-day-old rat testes displayed FT activity with a Vmax of 12.5 pmoles/mg protein/min and a Km of 22 microM, while purified Sertoli cell plasma membranes (SCPM) showed FT activity with a Vmax of 10 pmoles/mg protein/min and a Km of 18.2 microM for GDP-[14C]-L-fucose. Fucosyltransferase activities were 16.7 and 2.6 pmoles/mg protein/min in SC and SCPM, respectively; approximately 16% of FT activity is, therefore, on the cell surface. To test whether the expression of FT activity in SC was regulated by hormones and growth factors, SC were cultured in serum-free medium supplemented with insulin, transferrin, sodium selenite, and epidermal growth factor (medium 4F) or in 4F plus follicle-stimulating hormone, testosterone, hydrocortisone, and vitamin E (medium 8F). We found that FT activity in SC is not modulated by these hormones or growth factors (4F or 8F). For comparison with FT, galactosyltransferase (GalTase) activities in SC and SCPM were also determined. SC displayed GalTase activity with a Vmax of 50 pmoles/mg protein/min and a Km of 38.5 microM, while SCPM showed GalTase activity with a Vmax of 25 pmoles/mg protein/min and a Km of 20.8 microM for UDP-[3H]-galactose. Galactosyl-transferase activities were 29.2 and 9.6 pmoles/mg protein/min in SC and SCPM, respectively. Therefore, approximately 33% of the total cell GalTase activity was detected on the surface membranes of rat Sertoli cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1993 Oct
PMID:Surface-associated glycosyltransferase activities in rat Sertoli cells in vitro. 825 68

Nuclear factor kappa B (NF-kappa B) is believed to play an important role in the activation of human immunodeficiency virus (HIV) which causes acquired immunodeficiency syndrome (AIDS). Recent findings suggesting an involvement of reactive oxygen species in signal transduction pathways leading to NF-kappa B activation have encouraged the possible clinical use of antioxidants in blocking HIV activation. We have examined the effects of vitamin E and alpha-lipoate derivatives on NF-kappa B activation, and have observed that each of these antioxidants behave differently. Here we propose mechanisms of antioxidant actions in influencing cell signalling for NF-kappa B activation.
Mol Aspects Med 1993
PMID:Vitamin E and alpha-lipoate: role in antioxidant recycling and activation of the NF-kappa B transcription factor. 826 37

Vitamin E had an enhancing effect on active oxygen generation in concanavalin A (Con A)-stimulated alveolar macrophages (AMs) of rats. An inhibitor against protein kinase C (PKC) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) suppressed a large part of this vitamin E-related effect, but a calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) did not inhibit the increase of active oxygen formation by vitamin E treatment. These results suggest that the activation of PKC presumably relates to the enhancing effect of vitamin E on active oxygen formation in Con A-stimulated AMs.
Biochem Mol Biol Int 1993 Oct
PMID:A mechanism of vitamin E-enhanced active oxygen formation in concanavalin A-stimulated alveolar macrophage. 827 16

Vitamin E derivatives have been shown to inhibit tumor necrosis factor-induced NF-kappa B activation in human Jurkat T cells. The present report demonstrates that alpha-tocopheryl succinate directly blocks DNA binding activity of activated NF-kappa B, as well as the NF-kappa B activation induced by okadaic acid, an inhibitor of protein phosphatases 1 and 2A. In contrast, alpha-tocopherol, alpha-tocopheryl acetate and 2,2,5,7,8-pentamethyl-6-hydroxychromane have no effects. These observations suggest that the mechanism of alpha-tocopheryl succinate action against NF-kappa B is different from those of other vitamin E derivatives.
Biochem Mol Biol Int 1993 Nov
PMID:Inhibition of NF-kappa B DNA binding activity by alpha-tocopheryl succinate. 829 98

The effects of the natural antioxidants-anthocyans and vitamin E (in a solubilized pharmaceutical form) on carbon tetrachloride-induced liver injury in rats are studied. The changes in the activity of serum transaminases (ALAT and ASAT), the content of the reduced glutathione and cytochrome P-450 as well as the intensity of the processes of lipid peroxidation are assessed. The anthocyans exert a protective effect comparable to that of vitamin E on liver cells. The favorable effects of the combination of the antioxidants on the content of the reduced glutathione and on the processes of lipid peroxidation are more intensely expressed. The morphological changes occurring in hepatocytes correlate with the results of the biochemical studies. It is evident that both substances have a marked hepatoprotective activity.
Cell Mol Biol (Noisy-le-grand) 1993 Jun
PMID:Biochemical and morphological studies on the effects of anthocyans and vitamin E on carbon tetrachloride induced liver injury. 832 83

The present study was undertaken to test the hypothesis that activation of cell membrane associated protein kinase C (PKC) plays a role in stimulating cell membrane associated phospholipase A2 (PLA2) activity, and subsequent liberation of arachidonic acid (AA) under exposure of rabbit pulmonary arterial smooth muscle cells to the oxidant hydrogen peroxide (H2O2). Exposure of the smooth muscle cells to H2O2 dose-dependently stimulates [14C] AA release, and enhances the cell membrane associated PLA2 activity. Pretreatment of the cells with protein kinase C (PKC) inhibitors H7 and sphingosine prevent the cell membrane associated PLA2 activity, and AA release caused by H2O2. Treatment of the smooth muscle cells with H2O2 stimulates the cell membrane associated PKC activity. Pretreatment of the cells with an antioxidant vitamin E prevents H2O2 caused stimulation of the cell membrane associated PKC activity. The cell membrane associated PLA2 and PKC activities correlate linearly. These results suggest that H2O2 caused stimulation of the smooth muscle cell membrane associated PLA2 activity, and subsequent liberation of AA can occur through an increase in the activity of the cell membrane associated PKC.
Mol Cell Biochem 1993 May 12
PMID:Role of protein kinase C in oxidant--mediated activation of phospholipase A2 in rabbit pulmonary arterial smooth muscle cells. 835 Aug 69

The ESR spin-trapping technique has been used to investigate free radical generation in copper-challenged rats deficient in vitamin E and/or selenium. Radical adduct excreted in the bile was detected only from copper-challenged rats deficient in both vitamin E and selenium. The phenyl-N-t-butylnitrone radical adduct has hyperfine coupling constants of aN = 15.36 G and a beta H = 2.50 G and arises from the trapping of a radical formed from an endogenous molecular species. The induction of this radical species in vivo may be important in the increased toxicity of copper in rats deficient in both vitamin E and selenium. These findings support the proposal that dietary selenium and vitamin E can protect against lipid peroxidation and copper toxicity. The results obtained suggest that the presence of only one of these nutrients in the diet is enough to prevent the formation of this radical adduct at ESR-detectable levels, and they provide the most direct ESR evidence yet obtained for the involvement of in vivo lipid peroxidation in the toxicity of copper.
Mol Pharmacol 1993 Jul
PMID:Electron spin resonance evidence for free radical generation in copper-treated vitamin E- and selenium-deficient rats: in vivo spin-trapping investigation. 839 22

Lipid peroxidation, presumably the result of free radical-mediated injury, has been shown to occur during myocardial ischemia and reperfusion. Since vitamin E is a very effective, naturally occurring, chain-breaking antioxidant, it was investigated whether a vitamin E-supplemented diet increased myocardial tolerance towards ischemia and reperfusion in pigs. In addition to a standard diet which contained 30 mg vitamin E/kg (approximately daily vitamin E intake 30 mg), ten pigs were fed with 10 g vitamin E (all-rac-alpha-tocopherol acetate, Merck AG, Darmstadt, Germany) daily for at least 4 weeks. Ten control pigs remained on the standard diet. In an open chest preparation, the left anterior descending coronary artery was distally ligated for 45 min followed by 3 d of reperfusion. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was evaluated by sonomicrometry. Vitamin E concentrations in plasma and myocardium were measured by high-performance liquid chromatography. Global hemodynamic characteristics did not differ between the two groups. Oral pretreatment with vitamin E raised the plasma concentration of this vitamin from 1.1 +/- 0.3 to 5.0 +/- 1.0 mg/l and the myocardial content from 4.2 +/- 0.7 to 18.6 +/- 2.7 ng/mg fresh weight. Vitamin E treatment did not reduce infarct size, which amounted to 71.3 +/- 5% in the control group and to 71.7 +/- 8.2% in the treated animals. Furthermore, recovery of regional systolic shortening of the reperfused segment did not significantly differ in the two groups after 3 d of reperfusion; it measured 2 +/- 4% in the controls and 6 +/- 6% (p = 0.16) in the treated animals. Therefore, chronic, oral treatment with vitamin E which raised myocardial and plasma concentrations of this vitamin 4- to 5-fold did not increase myocardial tolerance towards ischemia and reperfusion in this animal model.
J Mol Cell Cardiol 1993 Jan
PMID:Failure of chronic, high-dose, oral vitamin E treatment to protect the ischemic, reperfused porcine heart. 844 Nov 76


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