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1.
2.
Acetaldehyde was found to form adducts with rat serum lipoproteins. The binding of [14C]acetaldehyde to lipoproteins was studied at low concentrations which are known to exist during ethanol oxidation. The amount of lipoprotein adducts was a linear function of acetaldehyde concentration up to 250 microM. Incubation of rat plasma low-density lipoproteins (LDL) with 200 microM acetaldehyde increased the disappearance rate of the 3H-label from the cholesterol ester moiety of LDL injected into normal rats. The data show that even low concentrations of acetaldehyde are capable of affecting LDL metabolism. These findings may provide an explanation for the low concentrations of serum LDL in alcoholics. 相似文献
3.
Different pathways of alcohol metabolism, the alcohol dehydrogenase pathway, the microsomal ethanol-oxidizing system and the catalase pathway are discussed. Alcohol consumption leads to accelerated ethanol metabolism by different mechanisms including an increased microsomal function. Microsomal induction leads to interactions of ethanol with drugs, hepatotoxic agents, steroids, vitamins and to an increased activation of mutagens/carcinogens. A number of ethanol-related complications may be explained by the production of its first metabolite, acetaldehyde, such as alterations of mitochondria, increased lipid peroxidation and microtubular alterations with its adverse effects on various cellular activities, including disturbances of cell division. Nutritional factors in alcoholics such as malnutrition are discussed especially with respect to its possible relation to cancer. 相似文献
4.
Electropore diameters, lifetimes, numbers, and locations in individual erythrocyte ghosts 总被引:14,自引:0,他引:14
Low light level video microscopy was used to study the diameter, lifetime, number, and location characteristics of electric field-induced pores (electropores) in erythrocyte ghosts. The diameter of electropores was probed by following the efflux of soluble fluorescent-tagged molecules out of the resealed ghost cytoplasmic compartments. After reaching a peak radius of at least 8.4 nm the electropores resealed within 200 ms to a radius of about 0.5 nm and stayed at that radius thereafter. Video sequences clearly show that pores are induced preferentially in the cathodal hemisphere. Pores induced in the hemisphere facing the positive electrode were either never greater than 0.5 nm in radius, much smaller in number if they were greater than 0.5 nm in radius, or shorter lived. Calculations indicated that an upper limit of 700 electropores were induced per membrane. 相似文献
5.
The effect of chronic alcohol feeding on lipid peroxidation in microsomes: lack of relationship to hydroxyl radical generation 总被引:1,自引:0,他引:1
S Shaw E Jayatilleke C S Lieber 《Biochemical and biophysical research communications》1984,118(1):233-238
Chronic alcohol feeding causes microsomal induction including increased generation of hydroxyl radicals. Ethanol induced liver injury may be mediated by lipid peroxidation for which hydroxyl radicals have been proposed as major mediators. Ethanol promotes lipid peroxidation when given acutely but also may serve as a hydroxyl radical scavenger. Therefore, we studied the acute and chronic effects of alcohol on microsomal lipid peroxidation and hydroxyl radical generation. Chronic alcohol feeding in rats increased microsomal generation of hydroxyl radicals but lipid peroxidation of endogenous lipid was inversely related to hydroxyl radical generation. Ethanol (50mM) had a slight inhibitory effect on hydroxyl radical production in peroxidizing microsomes, no effect on endogenous lipid peroxidation and enhanced the lysis of RBCs added as targets of peroxidation. Enhanced microsomal generation of hydroxyl radicals following chronic alcohol feeding is not an important mediator of lipid peroxidation. 相似文献
6.
Time Course of Steroid Biosynthesis and Metabolism in Haplopappus heterophyllus 总被引:4,自引:0,他引:4 下载免费PDF全文
A single dose of mevalonic acid-2-14C was administered simultaneously to 6 Haplopappus heterophyllus plants. They were harvested at intervals ranging from 3 days to 6 months. Four groups of biosynthetically related sterols were found to be radioactive in each plant, and the changes in radioactivity with time were studied. The most striking finding was a radioactive phenolic material present only in the 6-month plant, which had flowered. 相似文献
7.
Recombinant adenoviruses with large deletions generated by Cre-mediated excision exhibit different biological properties compared with first-generation vectors in vitro and in vivo. 总被引:13,自引:6,他引:7 下载免费PDF全文
In vivo gene transfer of recombinant E1-deficient adenoviruses results in early and late viral gene expression that elicits a host immune response, limiting the duration of transgene expression and the use of adenoviruses for gene therapy. The prokaryotic Cre-lox P recombination system was adapted to generate recombinant adenoviruses with extended deletions in the viral genome (referred to here as deleted viruses) in order to minimize expression of immunogenic and/or cytotoxic viral proteins. As an example, an adenovirus with a 25-kb deletion that lacked E1, E2, E3, and late gene expression with viral titers similar to those achieved with first-generation vectors and less than 0.5% contamination with E1-deficient virus was produced. Gene transfer was similar in HeLa cells, mouse hepatoma cells, and primary mouse hepatocytes in vitro and in vivo as determined by measuring reporter gene expression and DNA transfer. However, transgene expression and deleted viral DNA concentrations were not stable and declined to undetectable levels much more rapidly than those found for first-generation vectors. Intravenous administration of deleted vectors in mice resulted in no hepatocellular injury relative to that seen with first-generation vectors. The mechanism for stability of first-generation adenovirus vectors (E1a deleted) appeared to be linked in part to their ability to replicate in transduced cells in vivo and in vitro. Furthermore, the deleted vectors were stabilized in the presence of undeleted first-generation adenovirus vectors. These results have important consequences for the development of these and other nonintegrating vectors for gene therapy. 相似文献
8.
The characterization of a mammalian DNA structure-specific endonuclease. 总被引:24,自引:3,他引:21 下载免费PDF全文
The repair of some types of DNA double-strand breaks is thought to proceed through DNA flap structure intermediates. A DNA flap is a bifurcated structure composed of double-stranded DNA and a displaced single-strand. To identify DNA flap cleaving activities in mammalian nuclear extracts, we created an assay utilizing a synthetic DNA flap substrate. This assay has allowed the first purification of a mammalian DNA structure-specific nuclease. The enzyme described here, flap endonuclease-1 (FEN-1), cleaves DNA flap strands that terminate with a 5' single-stranded end. As expected for an enzyme which functions in double-strand break repair flap resolution, FEN-1 cleavage is flap strand-specific and independent of flap strand length. Furthermore, efficient flap cleavage requires the presence of the entire flap structure. Substrates missing one strand are not cleaved by FEN-1. Other branch structures, including Holliday junctions, are also not cleaved by FEN-1. In addition to endonuclease activity, FEN-1 has a 5'-3' exonuclease activity which is specific for double-stranded DNA. The endo- and exonuclease activities of FEN-1 are discussed in the context of DNA replication, recombination and repair. 相似文献
9.
Mammalian collagenase increases in early alcoholic liver disease and decreases with cirrhosis 总被引:11,自引:0,他引:11
K Maruyama L Feinman Z Fainsilber M Nakano I Okazaki C S Lieber 《Life sciences》1982,30(16):1379-1384
To determine if alterations in collagen degradation may contribute to the pathogenesis of fibrosis and cirrhosis, we studied the hepatic collagenase activity of 20 baboons given alcohol containing diets or control diets under carefully controlled experimental conditions. We also studied 28 patients whose livers were biopsied for diagnostic purposes. Hepatic collagenase activity was significantly increased in baboons with fatty liver compared to levels in normal, control fed animals [(1.98 +/- 0.19 vs 1.20 +/- 0.08 units (microgram collagen digested/hour/mg liver protein) +/- S.E.M., p less than 0.001)]. The increase in hepatic collagenase activity persisted at the stage of fibrosis when compared to the activity in control baboons (2.16 +/- 0.07 vs 1.20 +/- 0.08 units +/- S.E.M., p less than 0.001). A single cirrhotic baboon available for study had an hepatic collagenase activity of 1.58 units. Patients with hepatic fibrosis had significantly higher hepatic collagenase activity than those with fatty livers [(9.12 +/- 0.94 (n =14) vs 4.52 +/- 0.54 (n = 7) units +/- S.E.M., p less than 0.001)]. However, in the group with cirrhosis, hepatic collagenase was lower [(3.92 +/- 0.61 (n = 7) units +/- S.E.M., p less than 0.001)] than in the group with fibrosis. Our findings suggest that the development of cirrhosis is coincident with, or favored by a failure of hepatic collagen degradative enzymes to keep pace with hepatic collagen synthesis. 相似文献
10.
In rat liver microsomes, all-trans-[11,12-3H]retinoic acid was found to be metabolized to polar products in the presence of NADPH. One of the metabolites was coeluted with 4-hydroxyretinoic acid on reverse-phase high-pressure liquid chromatography (HPLC). This reaction required oxygen and was inhibited by carbon monoxide as well as aminopyrine, aniline, and ethanol, suggesting the involvement of cytochrome P-450. Isolated rat hepatocytes also metabolized all-trans[3H]retinoic acid to polar compounds, with an elution pattern on HPLC similar to that in microsomal preparations. Microsomal activity was compared in rats pair-fed with diets containing either ethanol or isocaloric carbohydrate for 4–6 weeks. Ethanol-fed rats showed enhanced microsomal retinoic acid metabolism (50%, P < 0.01) accompanied by increased microsomal cytochrome P-450 content (34%, P < 0.005). On the other hand, microsomal β-glucuronidation of retinoic acid in the presence of uridine diphosphoglucuronic acid (UDPGA) was not affected by chronic ethanol feeding. The increased hepatic microsomal cytochrome P-450-dependent metabolism of retinoic acid after chronic ethanol consumption may contribute to the accelerated catabolism of retinoic acid in vivo. 相似文献