Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of ethanol on functional activity of isolated perfused rat liver was studied (rate of O2 utilization, absorption of bromosulpholeine from perfusate, bile formation); total activity and activity in supernatant of nine marker enzymes were also determined (malate dehydrogenase, beta-glucuronidase, arylsulphatases A and B, beta-galactosidase, beta-glucosidase, acetylesterase, glucoso-6-phosphatase, alanine aminotransferase and aspartate aminotransferase). Activity of the enzymes was simultaneously studied in perfusate. Ethanol (0.5%) caused distinct impairement in functional activity of isolated liver; rate of bile formation and absorption of bromosulpholeine from perfusate were primarily altered. Degree of impairements in functional activity of liver tissue correlated with the concentration of ethanol in perfusate. In analysis of correlation between the total activity of the enzymes in liver tissue and their activity in supernatants and perfusate it was shown that the concentration (1%) of ethanol used did not produce damaye effect on plasma membranes and membranes of subcellular structures of hepatocytes, but, within certain limits, it displayed a stabilizing effect.
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PMID:[Effect of ethanol on stability of cell membranes in experiments using isolated liver]. 121 Jan 8

Heat-shock induction of heat-shock protein genes is due to a specific promoter element (the heat-shock element, HSE). This study used lacZ under HSE control (HSE-lacZ) to characterize HSE activity in Saccharomyces cerevisiae cells of different physiological states and differing genetic backgrounds. In batch fermentations HSE-lacZ induction by heat shock was maximal in exponential growth, and showed marked decline with the approach to stationary phase. Expression in the absence of heat shock was unaffected by growth phase, indicating that the growth-dependent expression of many yeast heat-shock genes uses promoter elements in addition to the HSE. Heat-induced expression was strongly influenced by the temperature at which cultures were grown. While basal, uninduced expression was constant during growth at different temperatures to 30 degrees C, induction by transfer to 39 degrees C was reduced by increases in growth temperature as low as 18-24 degrees C. Maximal HSE-lacZ induction (30- to 50-fold) was in cultures grown at low temperatures (18-24 degrees C), then heat shocked at 39 degrees C. Ethanol was a poor inducer. Mutations having little effect on HSE-lacZ expression included a respiratory petite; ubi4 (which inactivates the poly-ubiquitin gene); also ubc4 and ubc5 (which each inactivate one of the ubiquitin ligases involved in degradation of aberrant protein). pep4-3 increased both basal and induced beta-galactosidase about two-fold, probably because of slower turnover of this enzyme in pep4-3 strains.
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PMID:The determinants of heat-shock element-directed lacZ expression in Saccharomyces cerevisiae. 176 85

Many stresses, including elevated temperature and exposure to toxins or heavy metals, activate a stereotyped response of cultured cells known as the heat-shock response. The products of several highly conserved heat-shock genes (heat-shock proteins) protect the cells against subsequent stresses. The intracellular signal for the response is unknown, but may include the presence of damaged and abnormal proteins in the cell. Ethanol at high concentration (1.3 mol/L) has been shown to activate the heat-shock response in hamster ovary fibroblasts, suggesting that this response might be an important consequence of exposure of cells to ethanol and might mediate some of its cellular toxicity. To determine if lower concentrations of ethanol or its metabolites could activate a heat-shock response, we transfected COS-1 cells with a reporter gene (the Drosophila 70 kd heat-shock protein promoter fused to the beta-galactosidase gene), then exposed them to various compounds. Exposure to heat induced at least a threefold to fourfold increase in beta-galactosidase activity, whereas 1.3 mol/L ethanol induced a sixfold increase. Lower concentrations of ethanol (100 to 500 mmol/L) or acetaldehyde (100 to 500 mumol/L) did not induce a measurable heat-shock response. Similarly, high concentrations of metabolites generated during ethanol oxidation (10 mmol/L lactate or acetate) did not induce the response. We conclude that the heat-shock response cannot be detected with this assay system in COS-1 cells after short exposure to physiologically achievable concentrations of ethanol or its metabolites. However, it is possible that it is induced at a low level or in tissues directly exposed to alcoholic beverages (e.g., oropharynx, esophagus, and stomach).
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PMID:The heat-shock response in cultured cells exposed to ethanol and its metabolites. 250 9

In order to determine whether ethanol consumption alters the targeting of hepatic lysosomal enzymes to their organelles, we examined the sedimentation properties of lysosomal hydrolases in ethanol-fed rats and their pair-fed controls. Rats were fed a liquid diet containing either ethanol (36% of calories) or isocaloric maltose dextrin for one to five wk. Liver extracts were fractionated by Percoll density gradient centrifugation and fractions obtained were analyzed for the distribution of lysosomal marker enzymes. Heavy lysosomes were further purified from these gradients and the activity of specific hydrolases was determined. Compared with those from controls, isolated lysosomes from ethanol-fed rats showed a 20-50% reduction in the activity of lysosomal acid phosphatase and beta-galactosidase. Decreased intralysosomal hydrolase activity in ethanol-fed rats was associated with a significant redistribution of these enzymes as well as those of cathepsins B and L to lighter fractions of Percoll density gradients. This indicated an ethanol-elicited shift of these enzymes to lower density cellular compartments. In order to determine whether ethanol administration affects the synthesis and proteolytic maturation of hepatic procathepsin L, we conducted immunoblot analyses to quantify the steady-state levels of precursor and mature forms of cathepsin L in hepatic post-nuclear fractions. Ethanol administration caused a significant elevation in the steady-state level of the 39 kDa cathepsin L precursor relative to its 30 kDa intermediate and 25 kDa mature product. These results were confirmed by pulse-chase experiments using isolated hepatocytes exposed to [35S]methionine. Hepatocytes from both control and ethanol-fed rats incorporated equal levels of radioactivity into procathepsin L. However, during the chase period, the ratios of the 39 kDa procathepsin L to its 30 kDa intermediate and 25 kDa mature product in cells from ethanol-fed rats were 1.5-3-fold higher than those in controls. These results demonstrate that ethanol consumption caused a marked impairment in the processing of procathepsin L to mature enzyme, without affecting its synthesis. Taken together, our findings suggest that chronic ethanol consumption caused a deficiency in intralysosomal enzyme content by altering the trafficking and processing of these hydrolases into lysosomes.
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PMID:Ethanol consumption alters trafficking of lysosomal enzymes and affects the processing of procathepsin L in rat liver. 878 24

The effect of prenatal ethanol exposure on the intestinal maturation of rat fetuses was investigated to understand the nutritional alterations found in the offspring of alcoholic mothers. Female Wistar rats were maintained on solid diet and 25% ethanol solution as drinking fluid during pregnancy, and non-alcoholic isocaloric pregnant mothers were used as controls. At birth, intestines from unsuckled pups were removed for study. The weight and length of the intestine decreased significantly when ethanol was present in utero. Ultrastructural evaluation of the epithelium revealed loss of contact between neighboring enterocytes and abnormal dilation of the cisternae of the Golgi apparatus in ethanol-exposed pups. Further, increased lysosome-like vesiculation and enhanced lysosomal beta-galactosidase activity was observed in these neonates. The total number of absorptive enterocytes in the epithelium was reduced by 30% in ethanol-exposed neonates as compared to controls, due to altered cell growth and death during fetal life. Ethanol in utero stimulated epithelial cell migration which compensated cell loss, as demonstrated by 5'-Bromodeoxyuridine labeling. These findings could have important implications for the assimilation of nutrients and failure to thrive in infants with fetal alcohol syndrome.
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PMID:Ethanol in utero induces epithelial cell damage and altered kinetics in the developing rat intestine. 903 46

Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus cultures were treated with ethanol and tested for viability and beta-galactosidase activity. Exposure of the biomass of test cultures to 30%-55% ethanol (vol/vol) caused a 100% loss of viability and up to 15-fold increase in measurable beta-galactosidase activity in both streptococci and lactobacilli. Ethanol-treated cell suspensions could be stored for up to 6 months without loss of enzyme activity. The nonviable permeabilized biomass of the more active S. thermophilus was used to achieve up to 80% hydrolysis of lactose in aqueous solutions and non-fat milk.
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PMID:Permeabilization of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus with ethanol. 950 85

The physiological role of mitochondrial aldehyde dehydrogenase (ALD5) was investigated by analysis of the ald5 mutant (AKD321) in Saccharomyces cerevisiae. K(+)-activated ALDH activity of the ald5 mutant was about 80% of the wild-type in the mitochondrial fraction, while the respiratory activity of the ald5 mutant was greatly reduced. Cytochrome content was also reduced in the ald5 mutant. Enzymatic analysis revealed that the alcohol dehydrogenase activity of the ald5 mutant was higher than that of the wild-type, while glycerol 3-phosphate dehydrogenase activity was the same in the two strains. Ethanol as a carbon source or addition of 1 M NaCl with glucose as the carbon source in the growth medium increased beta-galactosidase activity from an ALD5-lacZ fusion. Overexpression of another mitochondrial ALDH gene (ALD7) had no effect on increasing respiratory function of the ald5 mutant, but showed improved growth on ethanol. These observations show that mitochondrial ALD5 plays a role in regulation or biosynthesis of electron transport chain components.
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PMID:Involvement of mitochondrial aldehyde dehydrogenase ALD5 in maintenance of the mitochondrial electron transport chain in Saccharomyces cerevisiae. 1058 50

Recombinant adeno-associated virus (rAAV) transduction is limited in vivo, yet can be enhanced by hydroxyurea, ultraviolet-irradiation, or adenovirus coinfection, possibly via mechanisms involving stress in the host cell. Because chronic ethanol induces oxidative stress, it was hypothesized that chronic ethanol would increase rAAV transduction in vivo. To test this hypothesis, rAAV encoding beta-galactosidase was given to Wistar rats that later received either ethanol diet or high-fat control diet via an enteral-feeding protocol for 3 weeks. Expression and activity of beta-galactosidase in the liver were increased nearly 5-fold by ethanol. The increase in transgene expression was inhibited by antioxidant diphenylene iodonium (DPI), which is consistent with the hypothesis that ethanol causes an increase in rAAV transduction via oxidative stress. Ethanol increased DNA synthesis only slightly; however, it increased the nuclear transcription factor kappaB (NFkappaB) 4-fold, a phenomenon also sensitive to DPI. Moreover, a 6-fold increase in rAAV transgene expression was observed in an acute ischemia-reperfusion model of oxidative stress. Transgene expression was transiently increased 24 hours after ischemia-reperfusion 3 days and 3 weeks after rAAV infection. Further, adenoviral expression of superoxide dismutase or IkappaBalpha superrepressor inhibited rAAV transgene expression caused by ischemia-reperfusion. Therefore, it is concluded that ethanol increases rAAV transgene expression via mechanisms dependent on oxidative stress, and NFkappaB likely through enhancement of cytomegaloviral (CMV) promoter elements. Alcoholic liver disease is an attractive target for gene therapy because consumption of ethanol could theoretically increase expression of therapeutic genes (e.g., superoxide dismutase). Moreover, this study has important implications for rAAV gene therapy and potential enhancement and regulation of transgene expression in liver.
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PMID:Chronic ethanol increases adeno-associated viral transgene expression in rat liver via oxidant and NFkappaB-dependent mechanisms. 1105 56

Chronic alcohol administration increases gut-derived endotoxin in the portal blood, which activates Kupffer cells through nuclear factor kappaB (NF-kappaB) to produce toxic mediators such as proinflammatory cytokines, leading to liver injury. Therefore, a long-term intragastric ethanol feeding protocol was used here to test the hypothesis that NF-kappaB inhibition would prevent early alcohol-induced liver injury. Adenoviral vectors encoding either the transgene for IkappaB superrepressor (AdIkappaB-SR) or the bacterial beta-galactosidase reporter gene (AdlacZ) were administered intravenously to Wistar rats. Animals were fed a high-fat liquid diet with either ethanol or isocaloric maltose-dextrin (control) for 3 weeks. There was no significant difference in mean urine alcohol concentrations between the groups fed ethanol. IkappaB-SR expression was increased for up to 2 weeks after injection, but was undetectable at 3 weeks. NF-kappaB activation was increased by ethanol and associated with up-regulation of tumor necrosis factor alpha (TNF-alpha). These increases were blunted significantly up to 2 weeks by AdIkappaB-SR. Dietary alcohol significantly increased liver to body weight ratios and serum alanine transaminase (ALT) levels in AdlacZ-treated animals, effects that were blunted significantly in AdIkappaB-SR-treated rats. Ethanol caused severe steatosis, inflammation, and focal necrosis in AdlacZ-treated animals. These pathologic changes were significantly decreased by AdIkappaB-SR. The protective effects of IkappaB-SR were significant 2 weeks after injection, but were lost at 3 weeks when IkappaB-SR was no longer expressed. Ethanol increased 4-hydroxynonenal as a maker of oxidative stress in both AdlacZ and AdIkappaB groups. These data support the hypothesis that NF-kappaB inhibition prevents early alcohol-induced liver injury even in the presence of oxidative stress.
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PMID:Delivery of IkappaB superrepressor gene with adenovirus reduces early alcohol-induced liver injury in rats. 1173 4

Ethanol is known to cause both tolerance and sensitization to endotoxin (lipopolysaccharide). It is also known that ethanol modulates the expression and activity of several intracellular signaling molecules and transcription factors in monocytes and Kupffer cells, the resident hepatic macrophages. Expression of CD14, the endotoxin receptor, is up-regulated following chronic exposure to endotoxin and ethanol. Ethanol-induced oxidative stress is important in the regulation of transcription factor activation and cytokine production by Kupffer cells. Thus, it was hypothesized that acute ethanol increases CD14 expression through a mechanism dependent upon oxidant production. This hypothesis was tested by overexpression of superoxide dismutase via recombinant adenovirus. Mice were infected with adenovirus (3 x 10(9) plaque-forming units, intravenously) containing either Cu,Zn superoxide dismutase (Ad.SOD1) or beta-galactosidase (Ad.lacZ), which caused significant expression of Cu,Zn-SOD in hepatocytes and Kupffer cells. Three days post-infection, mice were given saline or ethanol (5 g/kg, intragastrically). A significant increase in CD14 mRNA was observed 3 h after ethanol, and this increase was almost completely blocked in mice overexpressing Cu,Zn-SOD. Additionally, overexpression of SOD also blunted ethanol-induced activation of redox-sensitive transcription factors NFkappaB and AP-1 and production of cytokines. However, only inhibition of AP-1 with dominant-negative TAK1 but not NFkappaB by dominant-negative IkappaBalpha significantly blunted ethanol-induced increases in CD14, suggesting that AP-1 is important for CD14 transcriptional regulation. It is also shown here that NADPH oxidase is important in the increase in CD14 due to ethanol. Moreover, these data suggest that acute ethanol causes sensitization to endotoxin through mechanisms dependent upon oxidative stress.
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PMID:Up-regulation of CD14 in liver caused by acute ethanol involves oxidant-dependent AP-1 pathway. 1248 56


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