Disease relevance of Lct

• Four days of injections of D-thyroxine (200 micrograms/100 g body weight/day) produced a similar decrease of lactase activity [1].
• The delay in expression of maximal lactase activity might help to explain the vulnerability of this enzyme to acute mucosal insult such as occurs in viral gastroenteritis [2].
• RESULTS: Compared with transection, resection resulted in mucosal hyperplasia with significant decreases in the specific and total activities of sucrase, lactase, and maltase [3].
• In infants suffering from protein-calorie malnutrition, the decreased intestinal mucosal lactase specific activity could be due either to the protein-calorie malnutrition or to the commonly associated enteritis (viral or bacterial) and intestinal parasites [4].
• 5. Lactose 6'-O-sulphate neither behaved as a substrate nor acted as an inhibitor with respect to unsubstituted lactose and p-nitrophenyl beta-D-galactopyranoside when tested with lactase of suckling rat intestine and Escherichia coli beta-D-galactosidase (EC 3.2.1.23) [5].

Psychiatry related information on Lct

• A general hypothesis is proposed in order to clear up partly the mechanism involved in the stimulation of lactase activity by food deprivation in the adult rat [6].
• In other words, the fundamental pattern of significant depression of lactase expression occurred relatively independent of dietary modification [7].

High impact information on Lct

• A gene 'pill' associated with highly efficient and stable gene expression might be a practical and cost-effective strategy for even relatively mild disorders, such as lactase deficiency [8].
• In contrast, mutations E1750D and E1750G resulted in total loss of lactase and cellobiose activities, leaving only low ONP-glc and ONP-gal hydrolase activities detectable [9].
• This study provides the first evidence that rat LPH has its major catalytic site at E1750, representing all of the lactase and the majority of the phlorizin hydrolase activity [9].
• BACKGROUND/AIMS: Developmental changes of lactase activity along the proximal-to-distal axis of the small intestine are poorly understood [10].
• After 28 days, zones of reduced lactase expression were found in the duodenum and terminal ileum [10].

Chemical compound and disease context of Lct

• Although ethanol had been withdrawn at birth, pups issued from ethanol-treated mothers showed at 5 and 10 d postpartum decreased values of body weight, jejunal and ileal weights, and intestinal DNA concentration per unit of length, as well as lower specific and total activities in lactase and maltase, compared with controls [11].
• Adrenalectomy prevented the oral effect of spermine on sucrase- and maltase-specific activity but not on lactase-specific activity [12].
• The effects of bilateral adrenalectomy and subsequent force-feeding of L-tryptophan (30 mg/100 g body weight) on the activity of disaccharidases (lactase, sucrase, and maltase) in the jejunum and ileum were investigated [13].
• Results from these studies indicate that the birth weights of newborn rats exposed to cortisone in utero were significantly reduced; sucrase activity was prematurely induced and specific activities of lactase and maltase were enhanced in the intestines of the cortisone-treated newborns as contrasted with control animals [14].
• The study revealed that the activities of brush border sucrase, lactase and leucine aminopeptidase were stimulated only at high doses, viz 70 mg/kg (180 mumol/kg) body weight and above, whereas the activity of alkaline phosphate was depressed at comparatively low dose (17.5 mg/kg; 45 mumol/kg body weight) [15].

Biological context of Lct

• Thus, lactase activity in the intestine appears to be regulated during development predominantly by transcriptional mechanisms, while alterations during lactation, and along the proximal to distal gradient, are the result of other control mechanisms [16].
• In addition, we have demonstrated that in vivo bioluminescence imaging can be utilized for assessment of intestinal expression patterns of a luciferase reporter gene driven by lactase promoter regions in transgenic mice [17].
• The pattern of the 2.0-kb promoter transgene mRNA abundance most closely mimicked that of the endogenous lactase gene with respect to spatiotemporal restriction [17].
• Thus, a distinct 5'-region of the lactase promoter directs intestine-specific expression in the small intestine of transgenic mice, and regulatory sequences have been localized to a 1.2-kb region upstream of the lactase transcription start site [17].
• The series capacities of lactase and SGLT-1 varied in concert with each other over ontogeny and as lactose load was manipulated by experimental variation in litter size [18].

Anatomical context of Lct

• Analysis of the regional distribution of lactase mRNA along the small intestine at 14 days revealed that mRNA was high in the proximal three regions, but was dramatically lower in the distal regions [16].
• Membrane vesicles from developing (day 14-21) and adult Sprague-Dawley rats were enriched to a similar degree in brush border membrane marker enzyme activities (sucrase or lactase) compared with homogenate [19].
• Demonstration of a difference in expression of maximal lactase and sucrase activity along the villus in the adult rat jejunum [2].
• At weaning, the amount of lactase messenger RNA dropped specifically in the distal ileum [20].
• The intestine in continuity showed precocious appearance of active sucrase and accumulation along with maltase to greater than control levels, accompanied by a normal coincident decline in lactase activity and enterocyte life-span [21].

Associations of Lct with chemical compounds

• Absorption of quercetin-3-glucoside and quercetin-4'-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter [22].
• Ontogeny of intestinal safety factors: lactase capacities and lactose loads [18].
• Thyroxine-evoked decrease of jejunal lactase activity in adult rats [1].
• Lactase synthesis and processing was studied in 0- and 15-day-old rats after IP administration of [35S]methionine, and changes in precociously cortisone-induced sucrase-isomaltase were used as an internal control [23].
• Mucosal weight, protein, deoxyribonucleic acid, maltase, sucrase, lactase, alkaline phosphatase, leucine aminopeptidase, and fatty acids were all determined 3 and 12 days after methotrexate [24].

Physical interactions of Lct

• This applies particularly to the sucrase-isomaltase complex and the lactase-beta-glucosidase complex [25].

Regulatory relationships of Lct

• An increase in alkaline phosphatase and lactase activity was observed after 3-4 days in these colonies which could be enhanced to yield 90%-100% positive cells by the addition of dexamethasone to the medium while no sucrase-isomaltase activity was elicited [26].
• METHODS: To determine whether a physiological dose of insulin-like growth factor-1 would influence sucrase and lactase activity levels, 10-day-old suckling rat pups were treated with an oral gavage of insulin-like growth factor-1 [27].

Other interactions of Lct

• To test the above hypotheses we employed phlorizin (as an inhibitor of SGLT1) and N-(n-butyl)-deoxygalactonojirimycin (as an inhibitor of the lactase domain of LPH) in a rat everted-jejunal sac model [22].
• TNF-alpha had no effect on sucrase and maltase specific activity, but a slight augmentation of lactase specific activity was detected in the jejunum [28].
• IL-6 elicited sucrase and increased maltase specific activity in the whole small intestine, but lactase specific activity was not affected [28].
• Intraperitoneal (i.p.) injection of IL-1 beta increased the specific activity of sucrase in whole small intestine, whereas the specific activities of maltase and lactase were significantly enhanced only in the jejunum [28].
• The effect of prolactin on thymidine incorporation and tissue alkaline phosphatase, maltase and lactase activity was studied on jejunal explants from fetal, newborn and 2 week-old rats [29].

Analytical, diagnostic and therapeutic context of Lct

• Isograft lactase activities in both experimental transplant models were significantly higher than host intestinal lactase up to 28 days of age, suggesting that luminal factors are important in modulating lactase activity during the first 4 wk of postnatal life [30].
• Expression of lactase messenger (m) RNA and protein in rat small intestine during fetal and postnatal development was analyzed using in situ hybridization and immunohistochemistry [31].
• Mucosal lactase and sucrase-isomaltase were separately immunoprecipitated and analyzed by autoradiography after electrophoresis [23].
• Verification of the lactase site of rat lactase-phlorizin hydrolase by site-directed mutagenesis [9].
• To assess correlations between cellular differentiation and enzymatic maturation in the developing rat colon, tissue from fetal, suckling, weanling, and adult rats was analyzed by electron microscopy and assayed for lactase, alkaline phosphatase, and sodium-potassium-stimulated adenosine triphosphatase activities [32].

References