المؤلفون: Luis Martínez-Heredia, Manuel Muñoz-Torres, Raquel Sanabria-de la Torre, Ángela Jiménez-Ortas, Francisco Andújar-Vera, Trinidad González-Cejudo, Victoria Contreras-Bolívar, Sheila González-Salvatierra, José María Gómez-Vida, Cristina García-Fontana, Beatriz García-Fontana

المصدر: Frontiers in Endocrinology, Vol 14 (2024)

مصطلحات موضوعية: hypophosphatasia, tissue non-specific alkaline phosphatase, autoimmune diseases, gastrointestinal disorders, metabolic disease, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: IntroductionHypophosphatasia (HPP) is an inborn metabolic error caused by mutations in the ALPL gene encoding tissue non-specific alkaline phosphatase (TNSALP) and leading to decreased alkaline phosphatase (ALP) activity. Although the main characteristic of this disease is bone involvement, it presents a great genetic and clinical variability, which makes it a systemic disease.MethodsPatients were recruited based on biochemical assessments. Diagnosis was made by measuring serum ALP and pyridoxal 5-phosphate levels and finally by Sanger sequencing of the ALPL gene from peripheral blood mononuclear cells. Characterization of the new variants was performed by transfection of the variants into HEK293T cells, where ALP activity and cellular localization were measured by flow cytometry. The dominant negative effect was analyzed by co-transfection of each variant with the wild-type gene, measuring ALP activity and analyzing cellular localization by flow cytometry.ResultsTwo previously undescribed variants were found in the ALPL gene: leucine 6 to serine missense mutation (c.17T>C, L6S) affecting the signal peptide and threonine 167 deletion (c.498_500delCAC, T167del) affecting the vicinity of the active site. These mutations lead mainly to non-pathognomonic symptoms of HPP. Structural prediction and modeling tools indicated the affected residues as critical residues with important roles in protein structure and function. In vitro results demonstrated low TNSALP activity and a dominant negative effect in both mutations. The results of the characterization of these variants suggest that the pleiotropic role of TNSALP could be involved in the systemic effects observed in these patients highlighting digestive and autoimmune disorders associated with TNSALP dysfunction.ConclusionsThe two new mutations have been classified as pathogenic. At the clinical level, this study suggests that both mutations not only lead to pathognomonic symptoms of the disease, but may also play a role at the systemic level.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fendo.2023.1320516/fullTest; https://doaj.org/toc/1664-2392Test

الوصول الحر: https://doaj.org/article/8e59b00ac1ac4e5b95d3666530d33717Test

المؤلفون: Britt Opdebeeck, Ellen Neven, Stuart Maudsley, Hanne Leysen, Deborah Walter, Hilde Geryl, Patrick C. D’Haese, Anja Verhulst

المصدر: International Journal of Molecular Sciences; Volume 24; Issue 4; Pages: 3657

مصطلحات موضوعية: arterial media calcification, tissue non-specific alkaline phosphatase, inflammation, lipid/glucose homeostasis, mitochondrial pathway

جغرافية الموضوع: agris

الوصف: Arterial media calcification refers to the pathological deposition of calcium phosphate crystals in the arterial wall. This pathology is a common and life-threatening complication in chronic kidney disease, diabetes and osteoporosis patients. Recently, we reported that the use of a TNAP inhibitor, SBI-425, attenuated arterial media calcification in a warfarin rat model. Employing a high-dimensionality unbiased proteomic approach, we also investigated the molecular signaling events associated with blocking arterial calcification through SBI-425 dosing. The remedial actions of SBI-425 were strongly associated with (i) a significant downregulation of inflammatory (acute phase response signaling) and steroid/glucose nuclear receptor signaling (LXR/RXR signaling) pathways and (ii) an upregulation of mitochondrial metabolic pathways (TCA cycle II and Fatty Acid β-oxidation I). Interestingly, we previously demonstrated that uremic toxin-induced arterial calcification contributes to the activation of the acute phase response signaling pathway. Therefore, both studies suggest a strong link between acute phase response signaling and arterial calcification across different conditions. The identification of therapeutic targets in these molecular signaling pathways may pave the way to novel therapies against the development of arterial media calcification.

وصف الملف: application/pdf

العلاقة: Molecular Pathology, Diagnostics, and Therapeutics; https://dx.doi.org/10.3390/ijms24043657Test

الإتاحة: https://doi.org/10.3390/ijms24043657Test

المؤلفون: Hwa Kyung Nam, Emmanouil Emmanouil, Nan E. Hatch

المصدر: Frontiers in Dental Medicine, Vol 3 (2022)

مصطلحات موضوعية: craniofacial abnormalities, hypophosphatasia, pyrophosphate (PPi), craniosynostosis, fibroblast growth factor 23 (FGF23), tissue non-specific alkaline phosphatase (TNAP), Dentistry, RK1-715

الوصف: Hypophosphatasia is a rare heritable metabolic disorder caused by deficient Tissue Non-specific Alkaline Phosphatase (TNAP) enzyme activity. A principal function of TNAP is to hydrolyze the tissue mineralization inhibitor pyrophosphate. ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1) is a primary enzymatic generator of pyrophosphate and prior results showed that elimination of ENPP1 rescued bone hypomineralization of skull, vertebral and long bones to different extents in TNAP null mice. Current TNAP enzyme replacement therapy alleviates skeletal, motor and cognitive defects but does not eliminate craniosynostosis in pediatric hypophosphatasia patients. To further understand mechanisms underlying craniosynostosis development in hypophosphatasia, here we sought to determine if craniofacial abnormalities including craniosynostosis and skull shape defects would be alleviated in TNAP null mice by genetic ablation of ENPP1. Results show that homozygous deletion of ENPP1 significantly diminishes the incidence of craniosynostosis and that skull shape abnormalities are rescued by hemi- or homozygous deletion of ENPP1 in TNAP null mice. Skull and long bone hypomineralization were also alleviated in TNAP−/−/ENPP1−/− compared to TNAP−/−/ENPP1+/+ mice, though loss of ENPP1 in combination with TNAP had different effects than loss of only TNAP on long bone trabeculae. Investigation of a relatively large cohort of mice revealed that the skeletal phenotypes of TNAP null mice were markedly variable. Because FGF23 circulating levels are known to be increased in ENPP1 null mice and because FGF23 influences bone, we measured serum intact FGF23 levels in the TNAP null mice and found that a subset of TNAP−/−/ENPP1+/+ mice exhibited markedly high serum FGF23. Serum FGF23 levels also correlated to mouse body measurements, the incidence of craniosynostosis, skull shape abnormalities and skull bone density and volume fraction. Together, our results demonstrate that balanced expression of TNAP and ENPP1 enzymes are essential for microstructure and mineralization of both skull and long bones, and for preventing craniosynostosis. The results also show that FGF23 rises in the TNAP−/− model of murine lethal hypophosphatasia. Future studies are required to determine if the rise in FGF23 is a cause, consequence, or marker of disease phenotype severity.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fdmed.2022.846962/fullTest; https://doaj.org/toc/2673-4915Test

الوصول الحر: https://doaj.org/article/13c32af1e7d047dea6b7ad358ec3eb5dTest

المؤلفون: Goettsch, C., Strzelecka-Kiliszek, A., Bessueille, L., Quillard, T., Mechtouff, L., Pikula, S., Canet-Soulas, E., Millán, J. L., Fonta, Caroline, Magne, D.

المساهمون: Universitätsklinikum RWTH Aachen - University Hospital Aachen Aachen, Germany (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Nencki Institute of Experimental Biology, Polska Akademia Nauk = Polish Academy of Sciences = Académie polonaise des sciences (PAN), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS), Sarcomes osseux et remodelage des tissus calcifiés - INSERM U1238 (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hospices Civils de Lyon (HCL), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sanford Burnham Prebys Medical Discovery Institute, Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)

المصدر: ISSN: 0008-6363 ; Cardiovascular Research ; https://inserm.hal.science/inserm-03261168Test ; Cardiovascular Research, 2022, 118 (1), pp.84-96. ⟨10.1093/cvr/cvaa299⟩.

مصطلحات موضوعية: Tissue non-specific alkaline phosphatase, Cardiovascular calcification, Therapeutic target, Inhibition, Inflammation, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Cardiovascular calcification (CVC) is associated with increased morbidity and mortality. It develops in several diseases and locations, such as in the tunica intima in atherosclerosis plaques, in the tunica media in type 2 diabetes and chronic kidney disease, and in aortic valves. In spite of the wide occurrence of CVC and its detrimental effects on cardiovascular diseases (CVD), no treatment is yet available. Most of CVC involve mechanisms similar to those occurring during endochondral and/or intramembranous ossification. Logically, since tissue-nonspecific alkaline phosphatase (TNAP) is the key-enzyme responsible for skeletal/dental mineralization, it is a promising target to limit CVC. Tools have recently been developed to inhibit its activity and preclinical studies conducted in animal models of vascular calcification already provided promising results. Nevertheless, as its name indicates, TNAP is ubiquitous and recent data indicate that it dephosphorylates different substrates in vivo to participate in other important physiological functions besides mineralization. For instance, TNAP is involved in the metabolism of pyridoxal phosphate and the production of neurotransmitters. TNAP has also been described as an anti-inflammatory enzyme able to dephosphorylate adenosine nucleotides and lipopolysaccharide. A better understanding of the full spectrum of TNAP's functions is needed to better characterize the effects of TNAP inhibition in diseases associated with CVC. In this review, after a brief description of the different types of CVC, we describe the newly uncovered additional functions of TNAP and discuss the expected consequences of its systemic inhibition in vivo.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33070177; inserm-03261168; https://inserm.hal.science/inserm-03261168Test; https://inserm.hal.science/inserm-03261168/documentTest; https://inserm.hal.science/inserm-03261168/file/cvaa299.pdfTest; PUBMED: 33070177; WOS: 000743142600017

الإتاحة: https://doi.org/10.1093/cvr/cvaa299Test
https://inserm.hal.science/inserm-03261168Test
https://inserm.hal.science/inserm-03261168/documentTest
https://inserm.hal.science/inserm-03261168/file/cvaa299.pdfTest

المؤلفون: Luis Martínez-Heredia, Manuel Muñoz-Torres, Raquel Sanabria-de la Torre, Ángela Jiménez-Ortas, Francisco Andújar-Vera, Trinidad González-Cejudo, Victoria Contreras-Bolívar, Sheila González-Salvatierra, José María Gómez-Vida, Cristina García-Fontana, Beatriz García-Fontana

مصطلحات موضوعية: Endocrinology, Reproduction, Cell Metabolism, hypophosphatasia, tissue non-specific alkaline phosphatase, autoimmune diseases, gastrointestinal disorders, metabolic disease

الوصف: Introduction Hypophosphatasia (HPP) is an inborn metabolic error caused by mutations in the ALPL gene encoding tissue non-specific alkaline phosphatase (TNSALP) and leading to decreased alkaline phosphatase (ALP) activity. Although the main characteristic of this disease is bone involvement, it presents a great genetic and clinical variability, which makes it a systemic disease. Methods Patients were recruited based on biochemical assessments. Diagnosis was made by measuring serum ALP and pyridoxal 5-phosphate levels and finally by Sanger sequencing of the ALPL gene from peripheral blood mononuclear cells. Characterization of the new variants was performed by transfection of the variants into HEK293T cells, where ALP activity and cellular localization were measured by flow cytometry. The dominant negative effect was analyzed by co-transfection of each variant with the wild-type gene, measuring ALP activity and analyzing cellular localization by flow cytometry. Results Two previously undescribed variants were found in the ALPL gene: leucine 6 to serine missense mutation (c.17T>C, L6S) affecting the signal peptide and threonine 167 deletion (c.498_500delCAC, T167del) affecting the vicinity of the active site. These mutations lead mainly to non-pathognomonic symptoms of HPP. Structural prediction and modeling tools indicated the affected residues as critical residues with important roles in protein structure and function. In vitro results demonstrated low TNSALP activity and a dominant negative effect in both mutations. The results of the characterization of these variants suggest that the pleiotropic role of TNSALP could be involved in the systemic effects observed in these patients highlighting digestive and autoimmune disorders associated with TNSALP dysfunction. Conclusions The two new mutations have been classified as pathogenic. At the clinical level, this study suggests that both mutations not only lead to pathognomonic symptoms of the disease, but may also play a role at the systemic level.

العلاقة: https://figshare.com/articles/dataset/DataSheet_1_Systemic_effects_of_hypophosphatasia_characterization_of_two_novel_variants_in_the_ALPL_gene_docx/24933729Test

الإتاحة: https://doi.org/10.3389/fendo.2023.1320516.s001Test
https://figshare.com/articles/dataset/DataSheet_1_Systemic_effects_of_hypophosphatasia_characterization_of_two_novel_variants_in_the_ALPL_gene_docx/24933729Test

المؤلفون: WANG Liyou, LEI Yunyi, GAO Lei, CHENG Xiaocheng, JIANG Dan

المصدر: Di-san junyi daxue xuebao, Vol 42, Iss 11, Pp 1072-1077 (2020)

مصطلحات موضوعية: tissue non-specific alkaline phosphatase, myocardial infarction, procollagen type ⅰ c-peptide, procollagen ⅲ n-terminal peptide, Medicine (General), R5-920

الوصف: Objective To investigate the relationship of tissue non-specific alkaline phosphatase (TNAP) with myocardial fibrosis in patients after myocardial infarction (MI). Methods Forty-six acute MI patients admitted to our hospital from March to November 2019 were enrolled in this study and assigned as the MI group, and another 41 patients with negative findings in coronary angiograms during the same period were collected as the control group. The serum TNAP activity was detected by alkaline phosphatase kit. The serum contents of procollagen type ⅠC-peptide (PⅠCP) and procollagen Ⅲ N-terminal peptide (PⅢNP) were detected by enzyme-linked immunosorbent assay (ELISA). Myocardial tissues from 5 patients who died of MI were collected. Collagen fiber area of heart was detected by Sirius red staining and the expression of TNAP was detected by immunohistochemistry. Ten 8-week-old male C57BL/6J mice were randomly divided into sham group and MI group (n=5). In 2 weeks after MI, all mice were sacrificed, and collagen fiber area of heart was detected by Masson staining and the expression of TNAP was detected by immunohistochemistry. Results Compared with the control group, the MI group had significantly increased serum TNAP activity (8.49±3.30 King U/100 mL, P

وصف الملف: electronic resource

العلاقة: http://aammt.tmmu.edu.cn/Upload/rhtml/201912297.htmTest; https://doaj.org/toc/1000-5404Test

الوصول الحر: https://doaj.org/article/85538bb5862b45888221c4870619c5e8Test

المؤلفون: Baudry, Anne, Kellermann, Odile, Launay, Jean-Marie, Piétri, Mathéa, Schneider, B

المساهمون: Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Luc Maroteaux, Laurent Monassier

المصدر: 5-HT2B Receptors. From Molecular Biology to Clinical Applications
https://hal.science/hal-03421339Test
Luc Maroteaux
Laurent Monassier. 5-HT2B Receptors. From Molecular Biology to Clinical Applications, 35, Springer International Publishing, pp.53-70, 2021, The Receptors, 978-3-030-55919-9. ⟨10.1007/978-3-030-55920-5_3⟩

مصطلحات موضوعية: Serotonergic 2B receptor, signaling, stem cells, neuron, mineralized tissues, serotonin transporter, tissue-non specific alkaline phosphatase, miR-16, Prozac, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology

الوصف: International audience ; The serotonergic 2B receptor (5-HT 2B R), expressed in the central nervous system and at the periphery, contributes to the regulation of several physiological processes such as cardio-vascular, pulmonary, bone and neuronal functions. Due to its multifaceted roles, signaling pathways and cell targets controlled by the 5-HT 2B R are still the subject of intensive research. Here, we review how exploiting the dynamics of differentiation of the 1C11 neuronal stem cell line allows to identify several 5-HT 2B R-coupled signaling pathways and targets, among which the serotonin transporter, involved in the homeostasis of serotonergic neurons and their adaptive response to selective serotonin-reuptake inhibitors (SSRIs) like fluoxetine (Prozac ®). In addition mesoblastic stem cell lines permit to show that along the osteogenic differentiation, the 5-HT 2B R controls the activity of the tissue-non-specific alkaline phosphatase, a major enzyme for bone formation. Finally the 5-HT 2B R expressed by pulpal stem cells takes part to natural tooth repair upon 5-HT release by injury-activated platelets.

العلاقة: hal-03421339; https://hal.science/hal-03421339Test; https://hal.science/hal-03421339/documentTest; https://hal.science/hal-03421339/file/Baudry%20et%20al_Springer_The%20receptors_2021.pdfTest

الإتاحة: https://doi.org/10.1007/978-3-030-55920-5_3Test
https://hal.science/hal-03421339Test
https://hal.science/hal-03421339/documentTest
https://hal.science/hal-03421339/file/Baudry%20et%20al_Springer_The%20receptors_2021.pdfTest

المؤلفون: Fengdan Yu, Junyi Wang, Xiaojing Xu

المصدر: BMC Pediatrics, Vol 19, Iss 1, Pp 1-5 (2019)

مصطلحات موضوعية: Hypophosphatasia, Tissue non-specific alkaline phosphatase, Gene mutation, Pediatrics, RJ1-570

الوصف: Abstract Background Hypophosphatasia (HPP) is a rare hereditary disorder characterized by defective bone and tooth mineralization and deficiency of tissue non-specific alkaline phosphatase (TNAP) activity. The clinical presentation of HPP is highly variable, and the prognosis for the infantile form is poor. Case presentation This study reports a male infant diagnosed with lethal perinatal HPP. His gene analysis showed two heterozygous missense variants c.406C > T (p.R136C) and c.461C > T (p.A154V). The two mutations originated separately from his parents, consistent with autosomal recessive perinatal HPP, and the c.461C > T (p.A154V) was the novel mutation. Three-level structure model provide an explanation of the two mutated alleles correlating with the lethal phenotype of our patient. Results of SIFT, PolyPhen_2, and REVEL showed two mutations were pathogenic. Conclusions We demonstrated a case of perinatal lethal HPP caused by two heterozygous mutations, and one of which was novel. This finding will prove relevant for genetic counseling and perinatal gene testing for affected families.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12887-019-1478-7Test; https://doaj.org/toc/1471-2431Test

الوصول الحر: https://doaj.org/article/523d1de4d51c4dc4a7c9a2283573f33cTest

المؤلفون: Gámez Belmonte, María de los Reyes, Tena Garitaonaindia, Mireia, Hernández Chirlaque, Cristina, Córdova, Samir, Ceacero-Heras, Diego, Sánchez De Medina López-Huertas, Fermín, Martínez Augustín, María Olga

مصطلحات موضوعية: Methionine and choline diet, Metabolic syndrome, Biliary acids, Tissue non-specific alkaline phosphatase

الوصف: Funding: This research was funded by the Ministry of Economy and Competitivity of Spain, partly with Fondo Europeo de Desarrollo Regional FEDER funds [BFU2014-57736-P, AGL2014-58883-R, SAF2017-88457-R, AGL2017-85270-R] and by Junta de Andalucía [CTS235, CTS164]. MTG, RGB and CHC were supported by fellowships from the Ministry of Education. CIBERehd is funded by Instituto de Salud Carlos III. Institutional Review Board Statement: The study was conducted according to the guidelines of the Guide for the Care and Use of Laboratory Animals, and approved by the Animal Welfare Committee of the University of Granada (registry number: CEEA 01/03/2017–029). Informed Consent Statement: Not applicable for studies not involving humans. Acknowledgments: We gratefully acknowledge the assistance of Mercedes González and the rest of the group. ; The liver expresses tissue-nonspecific alkaline phosphatase (TNAP), which may participate in the defense against bacterial components, in cell regulation as part of the purinome or in bile secretion, among other roles. We aimed to study the role of TNAP in the development of hepatosteatosis. TNAP+/− haplodeficient and wild type (WT) mice were fed a control diet (containing 10% fat w/w) or the same diet deficient in methionine and choline (MCD diet). The MCD diet induced substantial weight loss together with hepatic steatosis and increased alanine aminotransferase (ALT) plasma levels, but no differences in IL-6, TNF, insulin or resistin. There were no substantial differences between TNAP+/− and WT mice fed the MCD diet. In turn, TNAP+/− mice receiving the control diet presented hepatic steatosis with alterations in metabolic parameters very similar to those induced by the MCD diet. Nevertheless, no weight loss, increased ALT plasma levels or hypoglycemia were observed. These mice also presented increased levels of liver TNF and systemic resistin and glucagon compared to WT mice. The phenotype of TNAP+/− mice fed a standard diet was normal. In conclusion, TNAP haplodeficiency induces ...

العلاقة: Gámez-Belmonte, R.; Tena-Garitaonaindia, M.; Hernández- Chirlaque, C.; Córdova, S.; Ceacero- Heras, D.; de Medina, F.S.; Martínez- Augustin, O. Deficiency in Tissue Non- Specific Alkaline Phosphatase Leads to Steatohepatitis in Mice Fed a High Fat Diet Similar to That Produced by a Methionine and Choline Deficient Diet. Int. J. Mol. Sci. 2021, 22, 51. [https://dx.doi.org/10.3390/ijms22010051Test]; http://hdl.handle.net/10481/66715Test

الإتاحة: https://doi.org/10.3390/ijms22010051Test
http://hdl.handle.net/10481/66715Test

المؤلفون: Reyes Gámez-Belmonte, Mireia Tena-Garitaonaindia, Cristina Hernández-Chirlaque, Samir Córdova, Diego Ceacero-Heras, Fermín Sánchez de Medina, Olga Martínez-Augustin

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 51, p 51 (2020)

مصطلحات موضوعية: methionine and choline diet, metabolic syndrome, biliary acids, tissue non-specific alkaline phosphatase, steatohepatitis, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: The liver expresses tissue-nonspecific alkaline phosphatase (TNAP), which may participate in the defense against bacterial components, in cell regulation as part of the purinome or in bile secretion, among other roles. We aimed to study the role of TNAP in the development of hepatosteatosis. TNAP +/− haplodeficient and wild type (WT) mice were fed a control diet (containing 10% fat w/w ) or the same diet deficient in methionine and choline (MCD diet). The MCD diet induced substantial weight loss together with hepatic steatosis and increased alanine aminotransferase (ALT) plasma levels, but no differences in IL-6, TNF, insulin or resistin. There were no substantial differences between TNAP +/− and WT mice fed the MCD diet. In turn, TNAP +/− mice receiving the control diet presented hepatic steatosis with alterations in metabolic parameters very similar to those induced by the MCD diet. Nevertheless, no weight loss, increased ALT plasma levels or hypoglycemia were observed. These mice also presented increased levels of liver TNF and systemic resistin and glucagon compared to WT mice. The phenotype of TNAP +/− mice fed a standard diet was normal. In conclusion, TNAP haplodeficiency induces steatosis comparable to that produced by a MCD diet when fed a control diet.

العلاقة: https://www.mdpi.com/1422-0067/22/1/51Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test; https://doaj.org/article/367873a338d74f3e894362e22376bf39Test

الإتاحة: https://doi.org/10.3390/ijms22010051Test
https://doaj.org/article/367873a338d74f3e894362e22376bf39Test