Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota

Malo, Madhu S.; Alam, Sayeda Nasrin; Mostafa, Golam; Zeller, Skye; Johnson, Paul V.; Mohammad, Nouri Nour; Chen, K T; Moss, Angela K.; Ramasamy, Sundaram; Faruqui, Arif A; Hodin, S; Malo, P S; Ebrahimi, Farzad; Biswas, Brishti; Narisawa, Sonoko; Millán, José Luis; Warren, H. Shaw; Kaplan, Jeffrey B.; Kitts, Christopher L.; Hohmann, Elizabeth L.; Hodin, Richard A.

doi:10.1136/gut.2010.211706

Cited by 178 publications

(201 citation statements)

References 36 publications

(52 reference statements)

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“…Recent evidence suggests that IAP expressed on apical surfaces of microvillus membranes of enterocytes detoxifies LPS in the intestine, thereby preventing inflammation, sustaining barrier function, and maintaining homeostasis within intestinal flora [501][502][503][504]. This hypothesis is supported by the analysis of IAP knockout mice [505,506]. In addition, LPS-dephosphorylating activity of gut-derived IAP has been suggested to be part of the endogenous hepatocyte defense system against LPS [507].…”

Section: Substrates and Catalytic Propertiesmentioning

confidence: 96%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

876

922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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Section: Substrates and Catalytic Propertiesmentioning

confidence: 96%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

876

922

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“…A legismertebb bélgyulladásos állatmodellben a dextrán szódium szulfát (DSS) indukálja a colitist. Ez a kémiai colitis makroszkóposan és mikroszkóposan megfeleltethető a humán vastagbél-gyulladásnak [34]. Az iAP-KO-egerekben a bélgyulla-dás szövettanilag súlyosabb volt, és iAP-tabletta adása csökkentette a colitis tüneteit mindkét vizsgált csoportban [35].…”

Section: ] (2 áBra)unclassified

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

et al. 2012

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Az intestinalis alkalikus foszfatáz enzim alapvető fontosságú a bélnyálkahártya épségének fenntartásában, mivel detoxifi kálni képes a lipopoliszacharidot, amely a Toll-like receptor-4 ligandja. A helytelen immunválasz, valamint a mucosalis barrier sérülése hozzájárulhat a gyulladásos bélbetegség és a coeliakia kialakulásához. Gyulladásos bél-betegségben szenvedő gyermekek gyulladt vastagbél-és újonnan diagnosztizált coeliakiás gyermekek duodenumnyálkahártyájában a csökkent intestinalis alkalikus foszfatáz és a Toll-like receptor-4 fehérjeexpresszió emelkedése következményesen fokozott lipopoliszacharid-aktivitással járhat, amely a szövetkárosító folyamatokat erősítheti. Az intestinalis alkalikus foszfatáz aktivitásának elősegítése colitises állatmodellben és terápiarezisztens colitis ulcerosás felnőtt betegekben csökkentette a bélgyulladás tüneteit. Ennek megfelelően a két vizsgált kórképben az enzim célzott intestinalis bejuttatása kiegészítő terápiás konzekvenciával is járhat a jövőben. Orv. Hetil., 2012Hetil., , 153, 1389Hetil., -1395

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“…Its location suggests an involvement in the uptake of nutrients, but its role has not yet been defined. A relationship with the process of fat absorption (4) and preservation of the normal homeostasis of the gut microbiota has been described previously (5) . IAP expression parallels that of other intestinal proteins involved in Ca absorption under vitamin D stimulation: Ca channel TRPV6, calbindin CD 9k , calcium sodium exchanger NCX 1 and Ca pump PMCAb1 (3,6,7) .…”

mentioning

confidence: 99%

Luminal calcium concentration controls intestinal calcium absorption by modification of intestinal alkaline phosphatase activity

2011

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Intestinal alkaline phosphatase (IAP) is a brush-border phosphomonoesterase. Its location suggests an involvement in the uptake of nutrients, but its role has not yet been defined. IAP expression parallels that of other proteins involved in Ca absorption under vitamin D stimulation. Experiments carried out in vitro with purified IAP have demonstrated an interaction between Ca and IAP. The gut is prepared to face different levels of Ca intake over time, but high Ca intake in a situation of a low-Ca diet over time would cause excessive entry of Ca into the enterocytes. The presence of a mechanism to block Ca entry and to avoid possible adverse effects is thus predictable. Thus, in the present study, Sprague -Dawley rats were fed with different amounts of Ca in the diet (0·2, 1 and 2 g%), and the percentage of Ca absorption (%Ca) in the presence and absence of L-phenylalanine (Phe) was calculated. The presence of Phe caused a significant increase in %Ca (52·3 (SEM 6·5) % in the presence of Phe v. 31·1 (SEM 8·9) % in the absence of Phe, regardless of the amount of Ca intake; paired t test, P¼ 0·02). When data were analysed with respect to Ca intake, a significant difference was found only in the group with low Ca intake (paired t test, P¼0·03). Additionally, IAP activity increased significantly (ANOVA, P,0·05) as Ca concentrations increased in the duodenal lumen. The present study provides in vivo evidence that luminal Ca concentration increases the activity of IAP and simultaneously decreases %Ca, acting as a minute-to-minute regulatory mechanism of Ca entry.

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Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota

Abstract: IAP is involved in the maintenance of normal gut microbial homeostasis and may have therapeutic potential against dysbiosis and pathogenic infections.

Cited by 178 publications

References 36 publications

Cellular function and molecular structure of ecto-nucleotidases

Cellular function and molecular structure of ecto-nucleotidases

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

Luminal calcium concentration controls intestinal calcium absorption by modification of intestinal alkaline phosphatase activity

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