scholarly journals Targeting the Intestinal Barrier to Prevent Gut-Derived Inflammation and Disease: A Role for Intestinal Alkaline Phosphatase

2021 ◽  
pp. 1-11
Author(s):  
Florian Kühn ◽  
Ruifeng Duan ◽  
Matthias Ilmer ◽  
Ulrich Wirth ◽  
Fatemeh Adiliaghdam ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Intestinal Barrier ◽  
Multiple Organ ◽  
Intestinal Alkaline Phosphatase ◽  
Alkaline Phosphatases ◽  
Gut Barrier Function ◽  
Proximal Small Intestine ◽  
Therapeutic Value ◽  
Organ Systems ◽  
Brush Border Enzyme

<b><i>Background:</i></b> Intestinal alkaline phosphatase (IAP) as a tissue-specific isozyme of alkaline phosphatases is predominantly produced by enterocytes in the proximal small intestine. In recent years, an increasing number of pathologies have been identified to be associated with an IAP deficiency, making it very worthwhile to review the various roles, biological functions, and potential therapeutic aspects of IAP. <b><i>Summary:</i></b> IAP primarily originates and acts in the intestinal tract but affects other organs through specific biological axes related to its fundamental roles such as promoting gut barrier function, dephosphorylation/detoxification of lipopolysaccharides (LPS), and regulation of gut microbiota. <b><i>Key Messages:</i></b> Numerous studies reporting on the different roles and the potential therapeutic value of IAP across species have been published during the last decade. While IAP deficiency is linked to varying degrees of physiological dysfunctions across multiple organ systems, the supplementation of IAP has been proven to be beneficial in several translational and clinical studies. The increasing evidence of the salutary functions of IAP underlines the significance of the naturally occurring brush border enzyme.

An Immunoprecipitation Assay for High Molecular Weight Alkaline Phosphatase in Human Serum

1989 ◽  
Vol 26 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Gerald A Maguire ◽  
Halima Adnan
Keyword(s):  
Molecular Weight ◽  
Alkaline Phosphatase ◽  
Liver Disease ◽  
High Molecular Weight ◽  
Solid Phase ◽  
Bone Alkaline Phosphatase ◽  
Intestinal Alkaline Phosphatase ◽  
Alkaline Phosphatases ◽  
Molecular Weight Form ◽  
Hepatic Malignancies

The serum of patients with obstructive liver disease may contain a high molecular weight form of alkaline phosphatase (high Mr alkaline phosphatase). The presence of this form of alkaline phosphatase is associated with hepatic malignancies. We have investigated the use of anti-alkaline phosphatase monoclonal antibodies which do not bind high Mr alkaline phosphatase in assays for high Mr alkaline phosphatase. Direct immunoprecipitation of liver and bone alkaline phosphatase with solid phase anti-liver alkaline phosphatase antibody (which also reacts with bone alkaline phosphatase) and measurement of the residual supernatant alkaline phosphatase activity led to a precise assay. Intestinal alkaline phosphatase interfered in this assay which, consequently, was of little use in the differential diagnosis of liver disease. Indirect precipitation of liver, bone, placental and intestinal alkaline phosphatase by soluble anti-liver alkaline phosphatase (which reacts with liver and bone alkaline phosphatases), soluble anti-intestinal alkaline phosphatase (which reacts with placental and intestinal alkaline phosphatases) and solid phase anti-mouse IgG led to an assay which, although less precise, showed more promise of being useful clinically.

scholarly journals Recombinant Human Tissue Non-Specific Alkaline Phosphatase Successfully Counteracts Lipopolysaccharide Induced Sepsis in Mice

2015 ◽  
pp. 731-738 ◽  
Author(s):  
B. BENDER ◽  
M. BARANYI ◽  
A. KEREKES ◽  
L. BODROGI ◽  
R. BRANDS ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Intravenous Injection ◽  
Human Tissue ◽  
Molecular Mechanisms ◽  
Multiple Organ ◽  
Control Group ◽  
Intestinal Alkaline Phosphatase ◽  
Specific Alkaline Phosphatase ◽  
Transgenic Rabbits ◽  
Rabbit Milk

Sepsis is a life threatening condition that arises when the body's response to an infection injures its own tissues and organs. Sepsis can lead to shock, multiple organ failure and death especially if not recognized early and treated promptly. Molecular mechanisms underlying the systemic inflammatory response syndrome associated with sepsis are still not completely defined and most therapies developed to target the acute inflammatory component of the disease are insufficient. In this study we investigated a possibility of combating sepsis in a mouse model by intravenous treatment with recombinant human tissue non-specific alkaline phosphatase (rhTNAP) derived from transgenic rabbit milk. We induced sepsis in mice by intraperitoneal injection of LPS and three hours later treated experimental group of mice by intravenous injection with rhTNAP derived from transgenic rabbits. Such treatment was proved to be physiologically effective in this model, as administration of recombinant rhTNAP successfully combated the decrease in body temperature and resulted in increased survival of mice (80 % vs. 30 % in a control group). In a control experiment, also the administration of bovine intestinal alkaline phosphatase by intravenous injection proved to be effective in increasing survival of mice treated with LPS. Altogether, present work demonstrates the redeeming effect of the recombinant tissue non-specific AP derived from milk of genetically modified rabbits in combating sepsis induced by LPS.

A fetal intestinal-type alkaline phosphatase in hepatocellular carcinoma tissue.

1977 ◽  
Vol 23 (9) ◽  
pp. 1615-1623 ◽  
Author(s):  
K Higashino ◽  
R Otani ◽  
S Kudo ◽  
Y Yamamura
Keyword(s):  
Alkaline Phosphatase ◽  
Electrophoretic Mobility ◽  
Normal Liver ◽  
Heat Stability ◽  
Intestinal Type ◽  
Intestinal Alkaline Phosphatase ◽  
Alkaline Phosphatases ◽  
Adult Type ◽  
Alkaline Phosphatase Isoenzyme ◽  
Hepatocellular Carcinoma Tissue

Abstract We examined 19 hepatoma tissues for alkaline phosphatase isoenzyme and found that six have both the Kasahara isoenzyme and an alkaline phosphatase with a unique electrophoretic mobility, in addition to the liver-type enzyme. From two of six carcinoma tissues, the abnormal enzyme was partly purified and subjected to a detailed analysis, which clarified that the abnormal enzyme resembled a fetal intestinal alkaline phosphatase in most of its enzymic and immunologic properties and also in properties that reflect enzyme structure. This fetal intestinal-type alkaline phosphatase was not found in 24 specimens of normal liver from adults. The relevance of fetal intestinal-type alkaline phosphatase to Kasahara isoenzyme and adult intestinal alkaline phosphatase is discussed. The fetal and adult intestinal alkaline phosphatases differ in electrophoretic mobility, heat stability, and reactivity with concanavalin A. The adult-type enzyme has two components; only the electrophoretically slower, neuraminidase-resistant one is described here.

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.

scholarly journals Characterization of human foetal intestinal alkaline phosphatase. Comparison with the isoenzymes from the adult intestine and human tumour cell lines

1983 ◽  
Vol 211 (3) ◽  
pp. 553-558 ◽  
Author(s):  
C M Behrens ◽  
C A Enns ◽  
H H Sussman
Keyword(s):  
Alkaline Phosphatase ◽  
Cell Line ◽  
Tumour Cell ◽  
Tumour Cell Line ◽  
Subunit Structure ◽  
Human Tumour ◽  
Intestinal Alkaline Phosphatase ◽  
Alkaline Phosphatases ◽  
Inhibition Studies

The molecular structure of human foetal intestinal alkaline phosphatase was defined by high-resolution two-dimensional polyacrylamide-gel electrophoresis and amino acid inhibition studies. Comparison was made with the adult form of intestinal alkaline phosphatase, as well as with alkaline phosphatases isolated from cultured foetal amnion cells (FL) and a human tumour cell line (KB). Two non-identical subunits were isolated from the foetal intestinal isoenzyme, one having same molecular weight and isoelectric point as placental alkaline phosphatase, and the other corresponding to a glycosylated subunit of the adult intestinal enzyme. The FL-cell and KB-cell alkaline phosphatases were also found to contain two subunits similar to those of the foetal intestinal isoenzyme. Characterization of neuraminidase digests of the non-placental subunit showed it to be indistinguishable from the subunits of the adult intestinal isoenzyme. This implies that no new phosphatase structural gene is involved in the transition from the expression of foetal to adult intestinal alkaline phosphatase, but that the molecular changes involve suppression of the placental subunit and loss of neuraminic acid from the non-placental subunit. Enzyme-inhibition studies demonstrated an intermediate response to the inhibitors tested for the foetal intestinal, FL-cell and KB-cell isoenzymes when compared with the placental, adult intestinal and liver forms. This result is consistent with the mixed-subunit structure observed for the former set of isoenzymes. In summary, this study has defined the molecular subunit structure of the foetal intestinal form of alkaline phosphatase and has demonstrated its expression in a human tumour cell line.

Crystal structure of rat intestinal alkaline phosphatase – Role of crown domain in mammalian alkaline phosphatases

2013 ◽  
Vol 184 (2) ◽  
pp. 182-192 ◽  
Author(s):  
Kaushik Ghosh ◽  
Debarati Mazumder Tagore ◽  
Rushith Anumula ◽  
Basanth Lakshmaiah ◽  
P.P.B.S. Kumar ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Alkaline Phosphatase ◽  
Intestinal Alkaline Phosphatase ◽  
Alkaline Phosphatases

Differentiation-dependent activation of the human intestinal alkaline phosphatase promoter by HNF-4 in intestinal cells

2005 ◽  
Vol 289 (2) ◽  
pp. G220-G226 ◽  
Author(s):  
Line Olsen ◽  
Simon Bressendorff ◽  
Jesper T. Troelsen ◽  
Jorgen Olsen
Keyword(s):  
Alkaline Phosphatase ◽  
Binding Site ◽  
Promoter Sequence ◽  
Computer Assisted ◽  
Intestinal Epithelial ◽  
Intestinal Alkaline Phosphatase ◽  
Cis Element ◽  
Nuclear Extracts ◽  
Brush Border Enzyme ◽  
Translational Start

The intestinal alkaline phosphatase gene ( ALPI) encodes a digestive brush-border enzyme, which is highly upregulated during small intestinal epithelial cell differentiation. To identify new putative promoter motifs responsible for the regulation of ALPI expression during differentiation of the enterocytes, we have conducted a computer-assisted cis-element search of the proximal human ALPI promoter sequence. A putative recognition site for the transcription factor hepatocyte nuclear factor (HNF)-4 was predicted at the positions from −94 to −82 in relation to the translational start site. The ability of HNF-4α to stimulate the expression from the ALPI promoter was investigated in the nonintestinal Hela cell line. Cotransfection with an HNF-4α expression vector demonstrated a direct activation of the ALPI promoter through this −94 to −82 element. EMSA showed that HNF-4α from nuclear extracts of differentiated intestinal epithelial cells (Caco-2) bound with high affinity to the predicted HNF-4 binding site. A 521 bp promoter fragment containing the HNF-4 binding site demonstrated a differentiation-dependent increase in promoter activity in Caco-2 cells. The presence of the HNF-4 binding site was necessary for this increase to occur.

scholarly journals The influence of metal ions on the orthophosphatase and inorganic pyrophosphatase activities of human alkaline phosphatase

1969 ◽  
Vol 112 (5) ◽  
pp. 699-701 ◽  
Author(s):  
D W Moss
Keyword(s):  
Alkaline Phosphatase ◽  
Metal Ions ◽  
Competitive Inhibitor ◽  
Inorganic Pyrophosphatase ◽  
Intestinal Alkaline Phosphatase ◽  
Alkaline Phosphatases ◽  
Low Concentrations ◽  
Pyrophosphatase Activity ◽  
Hydrolysis Of ◽  
Pyrophosphate Hydrolysis

1. The differential effects of adding Zn2+ and Mg2+ on the orthophosphatase and inorganic pyrophosphatase activities of human intestinal alkaline phosphatase were studied. 2. In the presence of excess of Zn2+, inorganic pyrophosphatase activity is inhibited. At higher concentrations of pyrophosphate, hydrolysis of this substrate takes place, but is inhibited competitively by the Zn2+–pyrophosphate complex. This complex also acts as a competitive inhibitor of orthophosphate hydrolysis. 3. Excess of Mg2+ also inhibits pyrophosphatase action by removal of substrate; at low concentrations, this ion activates pyrophosphatase, as is the case with orthophosphatase. 4. It is concluded that, when interactions between metal ions and pyrophosphate are taken into account, the effects of these ions are consistent with the view that alkaline phosphatases possess both orthophosphatase and inorganic pyrophosphatase activities.

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