Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have demonstrated that the specific activities of several proximal small intestinal mucosal enzymes fall in the aging rat. This reduction was due to a delay in the full expression of activity of these enzymes during epithelial cell transit from the crypt onto the intestinal villus. We now show in the ad libitum fed Fischer 344 rat that jejunal sucrase, maltase, and alkaline phosphatase specific activities do not fall gradually throughout the life span, but are reduced during senescence. Caloric restriction to 60% of ad libitum intake (DR) abolishes or delays this fall in enzyme activity. Jejunal mucosal immunoprecipitable sucrase-isomaltase (S-I) content also falls with age, but sucrase specific activity per molecule of S-I is less in the older ad libitum fed (approximately 45) than in the DR rats (approximately 60). Jejunal lactase activity falls gradually throughout the life span of ad libitum and DR rats, but lactase activity consistently was higher in DR animals. These observations indicate that DR alters the age-related changes in the activity of several enzymes in the rapidly replicating gut mucosa.
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PMID:Food restriction retards age-related biochemical changes in rat small intestine. 190 40

The present work investigates the ability of galactose to affect enterocyte differentiation during normal development in vivo. Energy intake has also been varied to take account of the fact that galactose is poorly metabolized in mice. Brush-border lactase, alpha-glucosidase, dipeptidylpeptidase-IV, aminopeptidase N, alkaline phosphatase and microvillus length were measured as markers of enterocyte differentiation in mice fed diets containing galactose (G diet), corn oil (E diet) or galactose + corn oil (G + E diet). Maintaining mice on a G instead of E diet reduced brush-border lactase activity and enterocyte migration rates; alpha-glucosidase, dipeptidylpeptidase-IV, aminopeptidase N and microvillus length expression increased and alkaline phosphatase activity remained unchanged. Feeding the G + E diet restored enterocyte migration rates, lactase, aminopeptidase N and dipeptidylpeptidase-IV activities to values found in mice fed the E diet. Galactose stimulation of alpha-glucosidase and microvillus length expression was, however, fully maintained in mice fed the G + E diet. Present results show that enterocyte differentiation is affected independently by varying dietary galactose and energy levels; that galactose effects always increase and energy effects usually decrease expression of enterocyte components and that energy stimulation of lactase activity is exceptional.
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PMID:Galactose effects on enterocyte differentiation in the mouse jejunum. 190 92

1. Change in digestive enzyme activities determined biochemically in brush-border membrane vesicles and cytochemically in isolated villi of lamb proximal intestine has been related to diet, intestinal structure and rumen development during the first 10 weeks of postnatal life. 2. Lactase activity halved, dipeptidylpeptidase IV activity doubled and aminopeptidase N and alkaline phosphatase activities remained constant during this period of development. Maintaining lambs on a milk replacer diet for 5 weeks after birth had no effect on this pattern of postnatal change in digestive enzyme activities. 3. Structural changes accompanying these selective effects on enzyme expression included a halving of villus height and a doubling of villus width. Villus surface area remained unaffected by these changes in height and width of villi. Crypt depth doubled during the first 10 weeks of postnatal life. Maintaining lambs on a milk replacer diet for 5 weeks did not affect this pattern of change in intestinal structure. 4. It appears from these results that postnatal decrease in lactase and increase in dipeptidylpeptidase IV activities are not regulated by factors such as diet, rumen development, or changes in intestinal structure. Attention is drawn to differences encountered between these results and a postnatal modification of glucose transport which clearly is dependent on diet.
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PMID:Postnatal development of lamb intestinal digestive enzymes is not regulated by diet. 190 59

The present study intended to evaluate the influences of Metagonimus yokogawai on the activities of brush border membrane bound enzymes of the small intestine. Mice were infected with 500 metacercariae respectively, and the worm recovery, morphological changes and enzyme activities were observed chronologically. A part of them were followed after the treatment. Recovered worms decreased in number continuously after the infection, and they were less than 10% after 2 weeks and almost zero after 28 weeks. Villous atrophy and stromal inflammation were found at two locations of the proximal jejunum from 2 weeks to 4 weeks after the infection. The enzymes, alkaline phosphatase, leucine aminopeptidase and disaccharidases (sucrase, lactase, maltase, and trehalase), showed lowered activities in the duodenum and proximal jejunum of the infected mice but they increased in the distal jejunum for the first two weeks. From three weeks after the infection, the activities were gradually recovered. In one week treated mice, they recovered the activities at 2 weeks from the treatment, but there found no differences of the activities between the 3 week treated group and infected controls. The present data reveal that M. yokogawai infection induces degenerative changes of the host's intestinal mucosa not only morphologically but functionally during the initial phase of infection. The lowered enzyme activities in acute metagonimiasis should be associated with malabsorption and diarrhea.
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PMID:Activities of brush border membrane bound enzymes of the small intestine in Metagonimus yokogawai infection in mice. 191 29

Oral administration of embelin (75 mg/kg per day, daily for 15 and 30 days) to male rats caused significant elevation in the uptake of D-glucose, L-alanine, L-leucine and calcium in small intestinal segments. Embelin also produced significant increases in intestinal brush border membrane-associated enzymes (sucrase, lactase, maltase, alkaline phosphatase and leucine aminopeptidase) in both intestinal homogenates and partially purified brush border membrane preparations. Significant increases were also noted for microsomal glucose-6-phosphatase and cytosolic lactate dehydrogenase. Increase in brush border membrane-associated total lipids, phospholipids, cholesterol, triacylglycerol, unesterified fatty acids and ganglioside sialic acid were seen but not in the cholesterol/phospholipid molar ratio. All these changes returned to control or near control levels following withdrawal of the drug.
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PMID:Effects of embelin, a male antifertility agent, on absorptive and digestive functions of rat intestine. 192 15

Caco-2 cells, which express spontaneous enterocytic differentiation at confluency, is one of the most relevant in vitro models for the study of differentiation and regulation of intestinal functions. However, these cells are normally cultured in the presence of 15-20% serum which renders extremely complex the identification of the factors involved in the regulation of both proliferation and differentiation. This study has been devoted to the establishment of chemically defined culture conditions which can sustain growth and differentiation of Caco-2 cells. The replacement of serum by ITS (insulin, transferrin, and selenium) allowed for normal structural and functional differentiation of cells as revealed by the establishment of cell polarity and the expression of brush-border membrane enzyme markers (sucrase, maltase, lactase, alkaline phosphatase, gamma-glutamyltransferase, aminopeptidase N, and dipeptidyl-dipeptidase IV), although the levels of sucrase activity were lower in ITS-supplemented medium. Coating petridishes with either type IV collagen or basement membrane proteins (Matrigel) did not improve the differentiation of cells, brush-border membrane enzyme activities being, in fact, lower when the cells were grown on these substrata. When triiodothyronine (T3, 5 x 10(-8) M) was added to the ITS-supplemented medium, disaccharidase and alkaline phosphatase activities were significantly increased while gamma-glutamyltransferase activity was diminished by T3 and stimulated by epidermal growth factor (1.6 x 10(-6) M). On the other hand, hydrocortisone (HC, 10(-6) M) did not modify disaccharidase and peptidase activities. These data clearly show that Caco-2 cells can be maintained in serum-free medium and that this system allows the study of the factors involved in the regulation of the differentiation of enterocyte in vitro.
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PMID:Caco-2 cells cultured in serum-free medium as a model for the study of enterocytic differentiation in vitro. 193 45

Several clonal sublines of HCT-116 human colon adenocarcinoma cells were isolated and characterized on the basis of their growth characteristics, intrinsic enterocyte-like differentiation (as assessed by alkaline phosphatase and lactase activities), and responses to butyrate, an inducer of colon tumor cell maturation. The HCT-116 sublines were found to be heterogeneous and several phenotypically distinct clones were identified. Further characterization of these clones indicated that the effects of butyrate on cell growth, alkaline phosphatase activity, and lactase activity were distinct and separable. The growth of all of the clones were inhibited by butyrate (IC50 values varied from 0.44 to 1.5 mM), but the effects of this agent on alkaline phosphatase and lactase activities varied widely. In several sublines butyrate had no effect on either enzyme while in others one or both activities were induced. Additionally, the binding of 125I-epidermal growth factor (EGF) to cell surface receptors was found to be proportional to the expression of lactase activity in the cell. The D3 clone and other sublines with intrinsic lactase activities greater than 100 nmol/mg/min expressed a class of high-affinity EGF receptors (e.g., D3 cells had 3.48 X 10(4) EGF receptors/cell with a kd of 0.61 nM). Other clones with less lactase activity had undetectable levels of 125I-EGF binding. In clones which exhibited greater than twofold increases in lactase activity in response to butyrate, the expression of a large number of low-affinity EGF receptors was also induced. In one such clone, the P1 subline, lactase activity was increased from 70 nmol/mg/min to 230 nmol/mg/min after 96 h in 2 mM butyrate, and the expression of EGF receptors was increased from undetectable levels to 1.18 X 10(5) EGF receptors/cell (kd of 3.2 nM). Northern blot analysis indicated that the increased 125I-EGF binding after butyrate treatment may have been due, in part, to a greater than twofold accumulation of EGF receptor mRNA. In addition, the expression of the messages for transforming growth factor alpha (TGF-alpha) and transforming growth factor beta (TGF-beta) was examined in butyrate-treated cells. While TGF-alpha mRNA levels were found to correlate with EGF receptor message levels in the HCT-116 clones, TGF-beta mRNA expression was not found to correlate with the butyrate-induced growth inhibition or with increases in EGF receptor expression, alkaline phosphatase activity, or lactase activity in these cells.
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PMID:Increased cell surface EGF receptor expression during the butyrate-induced differentiation of human HCT-116 colon tumor cell clones. 197 61

In order to develop an experimental model of symptomatic cryptosporidiosis in an immunosuppressed mammal, we investigated the pathophysiology of infection with Cryptosporidium and the humoral and cellular host responses in rnu/rnu (athymic) rats and their heterozygous (rnu/+) littermates by challenging suckling rats with greater than or equal to 2.5 x 10(6) Cryptosporidium oocytes oro-gastrically. Normal and immunodeficient animals were followed for onset and duration of infection (fecal oocysts), physiologic consequences (diarrhea, impaired weight gain, brush-border enzyme activities), and immunologic response (both B- and T-lymphocyte-mediated). Homozygosity for the rnu gene was associated with protracted cryptosporidial infections; shedding for up to 52 days occurred, and delay in weight gain was noted in rnu/rnu-infected compared with rnu/rnu-uninfected rats (p less than 0.05). In contrast, cryptosporidial challenge of rnu/+ rats resulted in self-resolving infections, occasionally with transient diarrhea lasting four days or less occurring 10-15 days after oro-gastric challenge. The latter animals mounted a cell-mediated immune response to Cryptosporidium: three months after challenge, five of five rnu/+ rats demonstrated positive skin test responses to a subcutaneous 3.5 micrograms dose of cryptosporidial antigen. Further, sera from 6 rnu/+ rats taken two to three months after oro-gastric oocyst challenge exhibited specific anticryptosporidial immunoglobulin binding (A405 = 0.96), compared to that of seven uninfected rnu/+ controls (A405 = 0.09, P less than 0.02). Macromolecules of 150, 105, and 88 kD in the Cryptosporidium antigen preparation were bound by serum immunoglobulin from previously infected, recovered rnu/+ rats. Two brush-border enzymes (lactase and alkaline phosphatase) were markedly reduced in the ileum 8-10 days after oro-gastric challenge in rats with diarrhea and oocyst shedding. We find the rnu/rnu (athymic, nude) rat provides a useful model for study of prolonged cryptosporidial infection with impaired weight loss, brush-border enzyme alteration and intermittent diarrhea. These studies further suggest that a T-lymphocyte population is involved in recovery from Cryptosporidium infection and that this recovery is associated with both cellular and humoral immune responses to specific cryptosporidial antigenic macromolecules. This model should open further avenues for the study of the pathogenesis and protective immunity in cryptosporidial infection.
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PMID:Intestinal cryptosporidiosis: pathophysiologic alterations and specific cellular and humoral immune responses in rnu/+ and rnu/rnu (athymic) rats. 199 41

The in vitro effects of human duodenal secretions and various combinations of its components on activity and release of enzymes from the human brush border were examined. Sucrase retained activity for 90 min in duodenal secretions, and maltase was almost as stable; lactase lost activity rapidly and alkaline phosphatase was of intermediate stability. Inactivation of lactase could only be partly (50%) attributed to luminal proteases, bile salts and phospholipids played no role. Rate of release of an enzyme from the brush border bore no relationship to its rate of inactivation. When individual proteases were studied, elastase was the most potent for releasing disaccharidases from the brush border; trypsin was ineffective alone but augmented the effect of elastase. Sucrase and maltase were activated by proteolytic release, but activation was abolished by simultaneous exposure of brush borders to bile salts. Lactase was released and rapidly inactivated by proteinases, while alkaline phosphatase appeared to be inactivated without significant release. These results show that there are significant interactions between luminal factors which have been inapparent when studying them in isolation. Loss of functionally useful enzyme does not follow release of sucrase or maltase from the brush border into the lumen but does follow release of lactase. Study of the susceptibility of lactase to inactivation by luminal factors in the various forms of lactose intolerance is warranted.
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PMID:Influence of duodenal secretions and its components on release and activities of human brush-border enzymes. 210 71

Administration of Embelin, an experimental antifertility agent, to male rats (20 mg/kg body wt/day, daily for 15 and 30 days), caused an elevation in the uptake of D-glucose, L-alanine, L-leucine, and calcium in the small intestinal segments. An increase was also noted in the intestinal brush border membrane (BBM)-associated enzymes, sucrase, lactase, maltase, alkaline phosphatase, and leucine aminopeptidase in both the intestinal homogenates and partially purified BBM preparations, particularly after 30-day administration of the drug. Embelin treatment also caused a significant increase in the microsomal glucose-6-phosphatase and the cytosolic enzyme, lactate dehydrogenase. In the Embelin-treated animals BBM-associated total lipids, phospholipids, cholesterol, triacylglycerol, unesterified fatty acids, ganglioside-sialic acids as well as the cholesterol/phospholipids molar ratio showed a considerable increase. All these changes in the Embelin-treated animals were restored back to the normal or near normal biochemical makeup when the drug therapy was withdrawn and the animals were allowed to recover for another 15 and 30 days, respectively.
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PMID:Changes in glucose/amino acid/calcium uptake and brush-border membrane-associated enzymes in rat small intestine after the administration of embelin (plant benzoquinone), an antifertility agent. 211 47


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