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.

scholarly journals Clinical Significance of Urinary Human Tissue Non-Specific Alkaline Phosphatase (hTNAP) in Pre-Eclampsia and Eclampsia

1997 ◽  
Vol 34 (4) ◽  
pp. 405-411 ◽  
Author(s):  
Mohamed Shaarawy ◽  
Samira Youssef El Mallah ◽  
Azza Abd El-Monem El-Yamani
Keyword(s):  
Alkaline Phosphatase ◽  
Pregnant Women ◽  
Human Tissue ◽  
Fetal Outcome ◽  
Tubular Damage ◽  
Third Trimester ◽  
Renal Tubular Damage ◽  
Specific Alkaline Phosphatase ◽  
Severity Of The Disease ◽  
Renal Tubular

The aim of this work was to determine the levels of urinary human tissue non-specific alkaline phosphatase (hTNAP) in pre-eclampsia and eclampsia in order to assess renal tubular damage. Urine samples were collected from 26 mild pre-eclamptic, 26 severe pre-eclamptic, 20 eclamptic patients and 20 healthy pregnant women (controls) in their late third trimester. Urinary hTNAP/creatinine (hTNAP/cr) in severe pre-eclampsia and eclampsia were significantly higher than in controls. Urinary hTNAP/cr was increased in 23%, 77% and 90% of cases of mild pre-eclampsia, severe pre-eclampsia and eclampsia, respectively, indicating that the increase correlates with the severity of the disease. Marked elevation or urinary hTNAP/cr was also associated with bad fetal outcome. These results provide additional evidence for renal tubular damage in pre-eclampsia and eclampsia.

A novel Sp1-relatedciselement involved in intestinal alkaline phosphatase gene transcription

1999 ◽  
Vol 276 (4) ◽  
pp. G800-G807 ◽  
Author(s):  
Jeong H. Kim ◽  
Shufen Meng ◽  
Amy Shei ◽  
Richard A. Hodin
Keyword(s):  
Alkaline Phosphatase ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Gene Activation ◽  
Regulatory Region ◽  
Intestinal Alkaline Phosphatase ◽  
Mobility Shift ◽  
Sv40 Promoter

We have used sodium butyrate-treated HT-29 cells as an in vitro model system to study the molecular mechanisms underlying intestinal alkaline phosphatase (IAP) gene activation. Transient transfection assays using human IAP-CAT reporter genes along with DNase I footprinting were used to localize a critical cis element (IF-III) corresponding to the sequence 5′-GACTGGGCGGGGTCAAGATGGA-3′. Deletion of the IF-III element resulted in a dramatic reduction in reporter gene activity, and IF-III was shown to function in the context of a heterologous (SV40) promoter in a cell type-specific manner, further supporting its functional role in IAP transactivation. Electrophoretic mobility shift assays revealed that IF-III binds Sp1 and Sp3, but these factors comprise only a portion of the total nuclear binding and appear to mediate only a small portion of its transcriptional activity. IF-III does not correspond to any previously characterized regulatory region from other intestine-specific genes. We have thus identified a novel, Sp1-related cis-regulatory element in the human IAP gene that appears to play a role in its transcriptional activation during differentiation in vitro.

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.

scholarly journals Activation of FoxO1/SIRT1/RANKL/OPG pathway may underlie the therapeutic effects of resveratrol on aging-dependent male osteoporosis

2020 ◽  
Author(s):  
Omnia Ameen ◽  
Rania I Yassien ◽  
Yahya M Naguib
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Molecular Mechanisms ◽  
Male Osteoporosis ◽  
Rat Femur ◽  
Albino Rats ◽  
Therapeutic Effects ◽  
Specific Alkaline Phosphatase ◽  
Bone Specific Alkaline Phosphatase ◽  
Age Dependent

Abstract Background Age-dependent male osteoporosis remains a poorly studied medical problem despite its significance. It is estimated that at least 1 of 5 men will suffer from osteoporotic consequences. Given that multiple mechanisms are involved in the process of senescence, much attention has been given to compounds with polymodal actions. To challenge such a health problem, we tested here the therapeutic potential of resveratrol in male osteoporosis. We also studied the possible molecular mechanisms that may underlie resveratrol effects. Methods Thirty male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control (3–4 months old weighing 150- 200 g receiving vehicle), aged (18–20 months old, weighing 350–400 g and receiving vehicle), and resveratrol treated aged (18–20 months old, weighing 350–400 g and receiving resveratrol 20 mg/kg/day for 6 weeks) groups. Assessment of serum calcium, phosphate, bone specific alkaline phosphatase, inflammatory cytokines, oxidative stress markers, and rat femur gene expression of FoxO1, SIRT1, RANKL and OPG proteins was carried out. Histopathological assessment of different levels of rat femur was also performed. Results Age-dependent osteoporosis resulted in significant increase in serum levels of phosphate, bone specific alkaline phosphatase, hsCRP, IL-1, IL-6, TNF-α, MDA, NO, and RANKL gene expression. However, there was significant decrease in serum level of GSH, and gene expression of FoxO1, SIRT1 and OPG. Osteoporotic changes were seen in femur epiphysis, metaphysis and diaphysis. Resveratrol restored significantly age-dependent osteoporotic changes. Conclusion We concluded that resveratrol can play an important role in the prevention of male osteoporosis. Resveratrol can counter the molecular changes in male osteoporosis via anti-inflammatory, anti-oxidant and gene modifying effects.

scholarly journals IIAEK Targets Intestinal Alkaline Phosphatase (IAP) to Improve Cholesterol Metabolism with a Specific Activation of IAP and Down-Regulation of ABCA1

2020 ◽  
Author(s):  
Asahi Takeuchi ◽  
Kentaro Hisamatsu ◽  
Natsuki Okumura ◽  
Yuki Sugimitsu ◽  
Emiko Yanase ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Molecular Probe ◽  
Small Intestinal Mucosa ◽  
Mrna Levels ◽  
Intestinal Alkaline Phosphatase ◽  
Down Regulation ◽  
Protein Levels ◽  
Abca1 Mrna

IIAEK (Ile-Ile-Ala-Glu-Lys, lactostatin) is a novel pentapeptide from bovine milk &beta;-lactoglobulin which lowers cholesterol levels. However, the molecular mechanisms underlying the suppression of intestinal cholesterol absorption by IIAEK are unknown. Therefore, we evaluated the effects of IIAEK on intestinal cholesterol metabolism in Caco-2 cells in a human intestinal model. We found that IIAEK significantly reduced the expression of intestinal cholesterol metabolism-associated genes, particularly that of the ATP-binding cassette transporter A1 (ABCA1) protein. Subsequently, we chemically synthesized a novel molecular probe, IIXEK, which can visualize a complex of target proteins interacting with photoaffinity-labeled IIAEK by fluorescent substances. Photoaffinity labeling and MS analysis with IIXEK for the rat small intestinal mucosa and intestinal lipid raft fractions of Caco-2 cells, we identified intestinal alkaline phosphatase (IAP) as a specific molecule interacting with IIAEK and discovered IIAEK common binding amino acid sequence, GFYLFVEGGR. Transfection of IAP siRNA counteracted the decrease in ABCA1 mRNA levels in Caco-2 cells. IIAEK significantly increased IAP mRNA and protein levels, and significantly decreased ABCA1 mRNA and protein levels in Caco-2 cells. In conclusion, we found that IIAEK targets IAP to improve cholesterol metabolism via a novel signaling pathway with a specific activation of IAP and down-regulation of intestinal ABCA1.

scholarly journals IIAEK Targets Intestinal Alkaline Phosphatase (IAP) to Improve Cholesterol Metabolism with a Specific Activation of IAP and Downregulation of ABCA1

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2859
Author(s):  
Asahi Takeuchi ◽  
Kentaro Hisamatsu ◽  
Natsuki Okumura ◽  
Yuki Sugimitsu ◽  
Emiko Yanase ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Bovine Milk ◽  
Cholesterol Absorption ◽  
Molecular Probe ◽  
Small Intestinal Mucosa ◽  
Intestinal Alkaline Phosphatase ◽  
Intestinal Cholesterol Absorption ◽  
Protein Levels

IIAEK (Ile-Ile-Ala-Glu-Lys, lactostatin) is a novel cholesterol-lowering pentapeptide derived from bovine milk β-lactoglobulin. However, the molecular mechanisms underlying the IIAEK-mediated suppression of intestinal cholesterol absorption are unknown. Therefore, we evaluated the effects of IIAEK on intestinal cholesterol metabolism in a human intestinal model using Caco-2 cells. We found that IIAEK significantly reduced the expression of intestinal cholesterol metabolism-associated genes, particularly that of the ATP-binding cassette transporter A1 (ABCA1). Subsequently, we chemically synthesized a novel molecular probe, IIXEK, which can visualize a complex of target proteins interacting with photoaffinity-labeled IIAEK by fluorescent substances. Through photoaffinity labeling and MS analysis with IIXEK for the rat small intestinal mucosa and intestinal lipid raft fractions of Caco-2 cells, we identified intestinal alkaline phosphatase (IAP) as a specific molecule interacting with IIAEK and discovered the common IIAEK-binding amino acid sequence, GFYLFVEGGR. IIAEK significantly increased IAP mRNA and protein levels while decreasing ABCA1 mRNA and protein levels in Caco-2 cells. In conclusion, we found that IIAEK targets IAP to improve cholesterol metabolism via a novel signaling pathway involving the specific activation of IAP and downregulation of intestinal ABCA1.

scholarly journals Characterization of human tissue-specific alkaline phosphatase.

1982 ◽  
Vol 30 (4) ◽  
pp. 1387-1392 ◽  
Author(s):  
KAZUYUKI HIRANO ◽  
YUICHI IIIZUMI ◽  
MAMORU SUGIURA ◽  
JUN MIYAZAKI ◽  
KAZUMASA MIKI ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Human Tissue ◽  
Tissue Specific ◽  
Specific Alkaline Phosphatase

scholarly journals Dose-related effects of extracorporeal shock waves on orthodontic tooth movement in rabbits

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Onur Demir ◽  
Nursel Arici
Keyword(s):  
Alkaline Phosphatase ◽  
Shock Waves ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Control Group ◽  
Specific Alkaline Phosphatase ◽  
Bone Specific Alkaline Phosphatase ◽  
Extracorporeal Shock Waves ◽  
Significant Difference ◽  
Maxillary Incisors

AbstractThe purpose of this animal study is to investigate the quantitative effects of extracorporeal shock waves applied at two different impulses and with two different applicators on orthodontic tooth movement. Thirty-five New Zealand rabbits were randomly divided into five groups (n = 7): the four experimental extracorporeal shock wave groups—focused/500 impulses, focused/1000 impulses, unfocused/500 impulses, and unfocused/1000 impulses—and the control group. Orthodontic tooth movement was achieved by application of reciprocal force between two maxillary incisors. In the experimental groups, animals received 500 or 1000 impulses of extracorporeal shock waves at 0.19 mJ/mm2 with focused or unfocused applicators depending on the group to which they belonged. These experiments were conducted on days 0, 7, and 14. Orthodontic tooth movement was measured with 0.01 mm accuracy at one-week intervals. On days 7 and 21, the bone-specific alkaline phosphatase levels were measured from blood samples. After 21 days, the animals were sacrificed and the area between the two maxillary incisors was stereologically examined. Orthodontic tooth movement in the focused/500 impulses and focused/1000 impulses groups was significantly increased compared to the control group. A significant difference in bone-specific alkaline phosphatase levels between the unfocused/500 impulses and control groups was found at 21st day. Stereological analysis showed that there were significant increases of the formation of new bone, connective tissue, and vessels in the experimental groups. The application of extracorporeal shock waves, especially with a focused applicator, could accelerate orthodontic tooth movement.

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