scholarly journals The Role of Intestinal Alkaline Phosphatase in Inflammatory Disorders of Gastrointestinal Tract

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jan Bilski ◽  
Agnieszka Mazur-Bialy ◽  
Dagmara Wojcik ◽  
Janina Zahradnik-Bilska ◽  
Bartosz Brzozowski ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Gastrointestinal Tract ◽  
Intestinal Inflammation ◽  
Stressful Events ◽  
Intestinal Lumen ◽  
Barrier Dysfunction ◽  
Intestinal Alkaline Phosphatase ◽  
Protective Mechanisms ◽  
Brush Border Enzyme

Over the past few years, the role of intestinal alkaline phosphatase (IAP) as a crucial mucosal defence factor essential for maintaining gut homeostasis has been established. IAP is an important apical brush border enzyme expressed throughout the gastrointestinal tract and secreted both into the intestinal lumen and into the bloodstream. IAP exerts its effects through dephosphorylation of proinflammatory molecules including lipopolysaccharide (LPS), flagellin, and adenosine triphosphate (ATP) released from cells during stressful events. Diminished activity of IAP could increase the risk of disease through changes in the microbiome, intestinal inflammation, and intestinal permeability. Exogenous IAP exerts a protective effect against intestinal and systemic inflammation in a variety of diseases and represents a potential therapeutic agent in diseases driven by gut barrier dysfunction such as IBD. The intestinal protective mechanisms are impaired in IBD patients due to lower synthesis and activity of endogenous IAP, but the pathomechanism of this enzyme deficiency remains unclear. IAP has been safely administered to humans and the human recombinant form of IAP has been developed. This review was designed to provide an update in recent research on the involvement of IAP in intestinal inflammatory processes with focus on IBD in experimental animal models and human patients.

scholarly journals Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis

2021 ◽  
Author(s):  
Siddhartha S Ghosh ◽  
Jing Wang ◽  
Paul J Yannie ◽  
Remy C Cooper ◽  
Yashnoor K Sandhu ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Lipid Absorption ◽  
Apical Surface ◽  
Barrier Dysfunction ◽  
Intestinal Alkaline Phosphatase ◽  
Over Expression ◽  
Intestinal Barrier Dysfunction

Rationale: Intestinal Alkaline Phosphatase (IAP) is secreted by enterocytes and is present on the apical surface. It not only detoxifies bacterial endotoxin lipopolysaccharide (LPS) in the gut lumen and limits intestinal inflammation but also restricts translocation of LPS into systemic circulation. Diet-induced intestinal barrier dysfunction and subsequent development of metabolic endotoxemia seen in diabetes and heart disease is associated with reduced IAP levels. To examine the direct effects of increased IAP expression on barrier function and development of metabolic diseases, we developed intestine-specific IAP transgenic mice (IAP Tg ) over-expressing human chimeric IAP. Objective: The aim of this study was to evaluate the effects of intestine-specific IAP overexpression on Western-type diet (WD)-induced atherosclerosis in Ldlr -/- mice. Methods and Results: IAPTg mice crossed into Ldlr -/- background (Ldlr-/-IAP Tg ) and Ldlr -/- littermates were fed WD for 16 weeks. Intestinal barrier dysfunction was assessed by monitoring plasma LPS levels and histological examination of colon. Over-expression of IAP attenuated WD-induced disruption of the colonic mucous layer, reducing intestinal barrier dysfunction and plasma LPS levels. Significant reduction in body, liver and adipose tissue weight was also seen in WD-fed Ldlr -/- IAP Tg mice. Plasma and hepatic lipids were also significantly reduced in WD-fed Ldlr -/- IAP Tg mice. Consistently, intestinal lipid absorption was attenuated in Ldlr -/- IAP Tg mice with reduced expression of apical lipid transporters (CD36, FATP4 and NPC1L1) and intracellular lipid transport proteins (FABP1/2, SCP2). Attenuation of WD-induced atherosclerosis in Ldlr -/- IAP Tg mice was demonstrated by significant reduction in arch and total aortic lesions as seen by enface analyses as well as significantly reduced atherosclerotic lesions in the ascending aorta of these mice. Conclusions: IAP overexpression improves intestinal barrier function by maintaining the integrity of the mucin layer in WD fed Ldlr -/- IAPTg mice and attenuates intestinal lipid absorption. Thus, by limiting translocation of gut-derived LPS and/or reducing plasma lipids, over-expression of IAP attenuates development of WD-induced atherosclerosis.

scholarly journals The role of intestinal alkaline phosphatase in pediatric inflammatory bowel and celiac diseases

2012 ◽  
Vol 153 (35) ◽  
pp. 1389-1395 ◽  
Author(s):  
Kriszta Molnár ◽  
Ádám Vannay ◽  
Erna Sziksz ◽  
Nóra Fanni Bánki ◽  
Áron Cseh ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Intestinal Inflammation ◽  
Therapeutic Option ◽  
Duodenal Mucosa ◽  
Mucosal Barrier ◽  
Toll Like Receptor ◽  
Intestinal Alkaline Phosphatase ◽  
Toll Like Receptor 4 ◽  
Inflammatory Bowel

Intestinal alkaline phosphatase enzyme plays a pivotal role in the maintenance of intestinal mucosal barrier integrity with the detoxification capacity of lipopolysaccharide, the ligand of Toll-like receptor 4. The inappropriate immune responses and the damage of the mucosal barrier may contribute to the initiation of inflammatory bowel and celiac diseases. In the inflamed colonic mucosa of children with inflammatory bowel disease and in the duodenal mucosa of newly diagnosed children with celiac disease, the decreased intestinal alkaline phosphatase and increased Toll-like receptor 4 protein expression may generate enhanced lipopolysaccharide activity, which may strengthen tissue damaging processes. The enhancement of intestinal alkaline phosphatase activity in an animal model of colitis and in therapy resistant, adult patients with ulcerative colitis reduced the symptoms of intestinal inflammation. In accordance with these results, the targeted intestinal administration of the enzyme in the two examined disorders may be a supplemental therapeutic option in the future. Orv. Hetil., 2012, 153, 1389–1395.

THE ROLE OF ALKALINE PHOSPHATASE IN INTESTINAL ABSORPTION: IV. THE EFFECTS OF VARIOUS PROTEINS ON LEVELS OF THE ENZYME IN INTESTINAL MUCOSA

1955 ◽  
Vol 33 (1) ◽  
pp. 89-92 ◽  
Author(s):  
Jules Tuba ◽  
Nester Dickie
Keyword(s):  
Alkaline Phosphatase ◽  
Intestinal Absorption ◽  
Intestinal Mucosa ◽  
Adult Male ◽  
Wheat Gluten ◽  
Male Rats ◽  
Dietary Proteins ◽  
Intestinal Alkaline Phosphatase ◽  
Egg Albumin

Fasted adult male rats were used to study the effect of dietary proteins on intestinal alkaline phosphatase. Groups of animals were offered one of several proteins; lactalbumin, egg albumin, zein, gelatin, wheat gluten, casein, and vitellin. Control animals had cellulose fed to them. The rats were sacrificed six hours after they were given the different diets. Alkaline phosphatase determinations with intestinal homogenates indicated that the two phosphoproteins, casein and vitellin, elevated levels of the enzyme significantly above fasting levels. Possible interpretations of these findings are discussed.

Pattern of rat intestinal brush-border enzyme gene expression changes with epithelial growth state

1995 ◽  
Vol 269 (2) ◽  
pp. C385-C391 ◽  
Author(s):  
R. A. Hodin ◽  
S. M. Chamberlain ◽  
S. Meng
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Brush Border ◽  
Longitudinal Axis ◽  
Mrna Levels ◽  
Intestinal Alkaline Phosphatase ◽  
Enzyme Gene ◽  
Growth State ◽  
Brush Border Enzyme ◽  
Epithelial Growth

Enterocyte growth and differentiation occur simultaneously within the epithelium, but little is known regarding any relationship between these two processes. Four rat models of small intestinal epithelial hypo- and hyperplasia (neonatal ontogeny, fasting/refeeding, hypo-/hyperthyroidism, and bombesin treatment) were used to study the regulation of enterocyte gene expression in relation to epithelial growth state. Mucosal scrapings, as well as crypt and villus cell populations, were subjected to Northern blot analyses using radiolabeled cDNA probes corresponding to lactase, intestinal alkaline phosphatase, villin, ornithine decarboxylase (ODC), and the actin control. In all four models, the hypoplastic (atrophic) condition is characterized by high levels of lactase and low levels of the 3.0-kb intestinal alkaline phosphatase mRNA, whereas under hyperplastic conditions this pattern is reversed. The changes in intestinal alkaline phosphatase and lactase are qualitatively similar along the longitudinal axis of the intestine and are proportional to the degree of hyperplasia, as verified by ODC mRNA levels. Furthermore, the crypt-villus axis of differentiation is maintained regardless of epithelial growth state. In conclusion, the pattern of brush-border enzyme gene expression changes as a function of epithelial growth state, indicating a previously unrecognized degree of plasticity to the state of enterocyte differentiation.

THE ROLE OF ALKALINE PHOSPHATASE IN INTESTINAL ABSORPTION I. THE KINETICS OF PHOSPHATASE ACTION ON VARIOUS SUBSTRATES

1953 ◽  
Vol 31 (1) ◽  
pp. 1-7
Author(s):  
Neil B. Madsen ◽  
Jules Tuba
Keyword(s):  
Alkaline Phosphatase ◽  
Average Energy ◽  
Inorganic Phosphorus ◽  
Intestinal Alkaline Phosphatase ◽  
Egg Lecithin ◽  
Michaelis Constants ◽  
Inhibition Studies ◽  
Kinetics Of ◽  
Hydrolysis Of

The kinetics of intestinal alkaline phosphatase action on sodium β-glycerophosphate, glucose 6-phosphate, and egg lecithin have been studied and compared. The Michaelis constants indicate that the enzyme shows considerably less affinity for lecithin than for the other two substrates, and the approximate ratio of activity with lecithin, glucose 6-phosphate, and sodium β-glycerophosphate is 11 : 78.5 : 100. The energies of activation for the hydrolysis of the three substrates do not differ appreciably and the average energy of activation is 14,500 calories per gram-mole. The similarity of the energies of activation together with results from inhibition studies indicate that in all probability the same enzyme is responsible for the release of inorganic phosphorus from each of the three substrates.

The Protective Role of Intestinal Alkaline Phosphatase in Necrotizing Enterocolitis

2010 ◽  
Vol 158 (2) ◽  
pp. 201
Author(s):  
J.S. Whitehouse ◽  
K.M. Riggle ◽  
D.P. Purpi ◽  
A.N. Mayer ◽  
K.A. Pritchard ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Necrotizing Enterocolitis ◽  
Protective Role ◽  
Intestinal Alkaline Phosphatase

W1548 Role of Lysophosphatidylcholine in Intestinal Alkaline Phosphatase Release and Restoration

2009 ◽  
Vol 136 (5) ◽  
pp. A-689
Author(s):  
Takanari Nakano ◽  
Ikuo Inoue ◽  
David H. Alpers ◽  
Rina Shinozaki ◽  
Jonathan D. Kaunitz ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Intestinal Alkaline Phosphatase

Role of intestinal alkaline phosphatase in calcium absorption

Bone ◽  
2016 ◽  
Vol 89 ◽  
pp. 68
Author(s):  
L.R. Brun ◽  
D. Lescano ◽  
S. Roma ◽  
J.L. Millán ◽  
A. Rigalli
Keyword(s):  
Alkaline Phosphatase ◽  
Calcium Absorption ◽  
Intestinal Alkaline Phosphatase
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