scholarly journals Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1648
Author(s):  
Daniel Liedtke ◽  
Christine Hofmann ◽  
Franz Jakob ◽  
Eva Klopocki ◽  
Stephanie Graser
Keyword(s):  
Alkaline Phosphatase ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Systemic Disease ◽  
Loss Of Function ◽  
Inorganic Pyrophosphate ◽  
Wide Range ◽  
Mineralization Processes ◽  
Tissue Nonspecific Alkaline Phosphatase

Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the ALPL gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme’s role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish.

scholarly journals TNAP as a New Player in Chronic Inflammatory Conditions and Metabolism

2021 ◽  
Vol 22 (2) ◽  
pp. 919
Author(s):  
Stephanie Graser ◽  
Daniel Liedtke ◽  
Franz Jakob
Keyword(s):  
Alkaline Phosphatase ◽  
Nervous System ◽  
Rare Disease ◽  
Molecular Processes ◽  
Inflammatory Conditions ◽  
Mineralization Processes ◽  
Tissue Nonspecific Alkaline Phosphatase ◽  
The Impact ◽  
Insight Into

This review summarizes important information on the ectoenzyme tissue-nonspecific alkaline phosphatase (TNAP) and gives a brief insight into the symptoms, diagnostics, and treatment of the rare disease Hypophosphatasia (HPP), which is resulting from mutations in the TNAP encoding ALPL gene. We emphasize the role of TNAP beyond its well-known contribution to mineralization processes. Therefore, above all, the impact of the enzyme on central molecular processes in the nervous system and on inflammation is presented here.

scholarly journals Extracellular pyrophosphate metabolism and calcification in vascular smooth muscle

2011 ◽  
Vol 301 (1) ◽  
pp. H61-H68 ◽  
Author(s):  
Ricardo Villa-Bellosta ◽  
Xiaonan Wang ◽  
José Luis Millán ◽  
George R. Dubyak ◽  
W. Charles O'Neill
Keyword(s):  
Alkaline Phosphatase ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Calcification ◽  
Endogenous Inhibitor ◽  
Inorganic Pyrophosphate ◽  
Inhibitory Role ◽  
Tissue Nonspecific Alkaline Phosphatase ◽  
Hydrolysis Of

Extracellular inorganic pyrophosphate (ePPi) is an important endogenous inhibitor of vascular calcification, but it is not known whether systemic or local vascular PPi metabolism controls calcification. To determine the role of ePPi in vascular smooth muscle, we identified the pathways responsible for ePPi production and hydrolysis in rat and mouse aortas and manipulated them to demonstrate their role in the calcification of isolated aortas in culture. Rat and mouse aortas contained mRNA for ectonucleotide pyrophosphatase/phosphodiesterases (NPP1–3), the putative PPi transporter ANK, and tissue-nonspecific alkaline phosphatase (TNAP). Synthesis of PPi from ATP in aortas was blocked by β,γ-methylene-ATP, an inhibitor of NPPs. Aortas from mice lacking NPP1 ( Enpp1−/−) did not synthesize PPi from ATP and exhibited increased calcification in culture. Although ANK-mediated transport of PPi could not be demonstrated in aortas, aortas from mutant ( ank/ank) mice calcified more in culture than did aortas from normal (ANK/ANK) mice. Hydrolysis of PPi was reduced 25% by β,γ-methylene-ATP and 50% by inhibition of TNAP. Hydrolysis of PPi was increased in cells overexpressing TNAP or NPP3 but not NPP1 and was not reduced in Enpp1−/− aortas. Overexpression of TNAP increased calcification of cultured aortas. The results show that smooth muscle NPP1 and TNAP control vascular calcification through effects on synthesis and hydrolysis of ePPi, indicating an important inhibitory role of locally produced PPi. Smooth muscle ANK also affects calcification, but this may not be mediated through transport of PPi. NPP3 is identified as an additional pyrophosphatase that could influence vascular calcification.

scholarly journals Neutrophil Extracellular Traps in Periodontitis

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1494 ◽  
Author(s):  
Antonio Magán-Fernández ◽  
Sarmad Muayad Rasheed Al-Bakri ◽  
Francisco O’Valle ◽  
Cristina Benavides-Reyes ◽  
Francisco Abadía-Molina ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Decisive Role ◽  
Neutrophil Extracellular Traps ◽  
Gingival Tissue ◽  
Multifactorial Disease ◽  
Extracellular Traps ◽  
Wide Range ◽  
Neutrophil Response ◽  
Inflammatory Component

Neutrophils are key cells of the immune system and have a decisive role in fighting foreign pathogens in infectious diseases. Neutrophil extracellular traps (NETs) consist of a mesh of DNA enclosing antimicrobial peptides and histones that are released into extracellular space following neutrophil response to a wide range of stimuli, such as pathogens, host-derived mediators and drugs. Neutrophils can remain functional after NET formation and are important for periodontal homeostasis. Periodontitis is an inflammatory multifactorial disease caused by a dysbiosis state between the gingival microbiome and the immune response of the host. The pathogenesis of periodontitis includes an immune-inflammatory component in which impaired NET formation and/or elimination can be involved, contributing to an exacerbated inflammatory reaction and to the destruction of gingival tissue. In this review, we summarize the current knowledge about the role of NETs in the pathogenesis of periodontitis.

scholarly journals Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update

2020 ◽  
Vol 9 (4) ◽  
pp. 1096
Author(s):  
Jessica Gambardella ◽  
Angela Lombardi ◽  
Marco Bruno Morelli ◽  
John Ferrara ◽  
Gaetano Santulli
Keyword(s):  
Human Disease ◽  
Calcium Release ◽  
Current Knowledge ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Loss Of Function ◽  
Genome Wide ◽  
Inositol 1,4,5 Trisphosphate ◽  
Human Disorders

Inositol 1,4,5-trisphosphate receptors (ITPRs) are intracellular calcium release channels located on the endoplasmic reticulum of virtually every cell. Herein, we are reporting an updated systematic summary of the current knowledge on the functional role of ITPRs in human disorders. Specifically, we are describing the involvement of its loss-of-function and gain-of-function mutations in the pathogenesis of neurological, immunological, cardiovascular, and neoplastic human disease. Recent results from genome-wide association studies are also discussed.

scholarly journals Evolving Role of Microparticles in the Pathophysiology of Endothelial Dysfunction

2013 ◽  
Vol 59 (8) ◽  
pp. 1166-1174 ◽  
Author(s):  
Fina Lovren ◽  
Subodh Verma
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Vascular Endothelial Cells ◽  
Current Knowledge ◽  
Early Event ◽  
Prognostic Information ◽  
Vascular Events ◽  
Wide Range

BACKGROUND Endothelial dysfunction is an early event in the development and progression of a wide range of cardiovascular diseases. Various human studies have identified that measures of endothelial dysfunction may offer prognostic information with respect to vascular events. Microparticles (MPs) are a heterogeneous population of small membrane fragments shed from various cell types. The endothelium is one of the primary targets of circulating MPs, and MPs isolated from blood have been considered biomarkers of vascular injury and inflammation. CONTENT This review summarizes current knowledge of the potential functional role of circulating MPs in promoting endothelial dysfunction. Cells exposed to different stimuli such as shear stress, physiological agonists, proapoptotic stimulation, or damage release MPs, which contribute to endothelial dysfunction and the development of cardiovascular diseases. Numerous studies indicate that MPs may trigger endothelial dysfunction by disrupting production of nitric oxide release from vascular endothelial cells and subsequently modifying vascular tone. Circulating MPs affect both proinflammatory and proatherosclerotic processes in endothelial cells. In addition, MPs can promote coagulation and inflammation or alter angiogenesis and apoptosis in endothelial cells. SUMMARY MPs play an important role in promoting endothelial dysfunction and may prove to be true biomarkers of disease state and progression.

scholarly journals Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽  
2020 ◽  
Author(s):  
Kaitlyn A Dorsett ◽  
Michael P Marciel ◽  
Jihye Hwang ◽  
Katherine E Ankenbauer ◽  
Nikita Bhalerao ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Sialic Acids ◽  
Invasion Resistance ◽  
Cell Behaviors ◽  
Molecular Events ◽  
Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

scholarly journals Role of active patient involvement in undergraduate medical education: a systematic review

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e037217
Author(s):  
Stijntje Willemijn Dijk ◽  
Edwin Johan Duijzer ◽  
Matthias Wienold
Keyword(s):  
Systematic Review ◽  
Medical Education ◽  
Undergraduate Medical Education ◽  
Patient Involvement ◽  
Current Knowledge ◽  
Daily Practice ◽  
Pubmed Database ◽  
Wide Range ◽  
Active Patient

ObjectivesTo identify the scope of active patient involvement in medical education, addressing the current knowledge gaps relating to rationale and motivation for involvement, recruitment and preparation, roles, learning outcomes and key procedural contributors.MethodsThe authors performed a systematic search of the PubMed database of publications between 2003 and 2018. Original studies in which patients take on active roles in the development, delivery or evaluation of undergraduate medical education and written in English were eligible for inclusion. Included studies’ references were searched for additional articles. Quality of papers was assessed using the Mixed Methods Appraisal Tool.Results49 articles were included in the review. Drivers for patient involvement included policy requirements and patients’ own motivations to contribute to society and learning. Patients were engaged in a variety of educational settings in and outside of the hospital. The vast majority of studies describe patients taking on the role of a patient teacher and formative assessor. More recent studies suggest that patients are increasingly involved in course and curriculum development, student selection and summative assessment. The new body of empirical evidence shows the wide range of learning objectives was pursued through patient participation, including competencies as professional, communicator, collaborator, leader and health advocate, but not scholar. Measures to support sustainable patient involvement included longitudinal institutional incorporation, patient recruitment and/or training, resource support and clear commitment by faculty. The importance and advantages of patient involvement were highlighted by students, faculty and patients themselves; however, organisations must continue to consider, monitor and take steps to mitigate any potential harms to patients and students.DiscussionThis systematic review provides new knowledge and practical insights to physicians and faculty on how to incorporate active patient involvement in their institutions and daily practice, and provides suggested action points to patient organisations wishing to engage in medical education.

Stomatal conductance scales with petiole xylem traits in Populus genotypes

2016 ◽  
Vol 43 (6) ◽  
pp. 553 ◽  
Author(s):  
Caroline A. Brocious ◽  
Uwe G. Hacke
Keyword(s):  
Stomatal Conductance ◽  
Current Knowledge ◽  
Hybrid Poplar ◽  
Leaf Size ◽  
Exchange Capacity ◽  
Vein Density ◽  
Wide Range ◽  
Major Vein ◽  
Size And Morphology

Progress has been made in linking water transport in leaves with anatomical traits. However, most of our current knowledge about these links is based on studies that sampled phylogenetically distant species and covered a wide range of leaf size and morphology. Here we studied covariation of leaf anatomical traits and hydraulic capacity in five closely related hybrid poplar genotypes. Variation in stomatal conductance and leaf hydraulic conductance was not linked to vein density or other anatomical lamina properties. A strong correlation was found between stomatal conductance and the transport capacity of the petiole, estimated from the diameter and number of xylem vessels. An inverse relationship existed between leaf size and major vein density. The role of bundle sheath extensions is discussed. Our data suggests that petiole xylem is an important predictor of gas exchange capacity in poplar leaves.

scholarly journals Structural Evidence for a Functional Role of Human Tissue Nonspecific Alkaline Phosphatase in Bone Mineralization

2001 ◽  
Vol 276 (33) ◽  
pp. 31171-31178 ◽  
Author(s):  
Etienne Mornet ◽  
Enrico Stura ◽  
Anne-Sophie Lia-Baldini ◽  
Torgny Stigbrand ◽  
André Ménez ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Human Tissue ◽  
Functional Role ◽  
Bone Mineralization ◽  
Tissue Nonspecific Alkaline Phosphatase

The role of the zinc transporter SLC30A2/ZnT2 in transient neonatal zinc deficiency

Metallomics ◽  
2017 ◽  
Vol 9 (10) ◽  
pp. 1352-1366 ◽  
Author(s):  
Yarden Golan ◽  
Taiho Kambe ◽  
Yehuda G. Assaraf
Keyword(s):  
Zinc Deficiency ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Zinc Transporter ◽  
Loss Of Function ◽  
Breastfed Infants ◽  
Nursing Mothers ◽  
Novel Approaches

Transient neonatal zinc deficiency (TNZD) results from loss of function mutations in theSLC30A2/ZnT2gene. Nursing mothers harboring this defective zinc transporter produce zinc-deficient milk. Consequently, their exclusively breastfed infants develop severe zinc deficiency. The present review summarizes our current knowledge onSLC30A2/ZnT2gene mutations and highlights the molecular mechanisms underlying this zinc deficiency. We further propose novel approaches for the early diagnosis and prevention of TNZD.

Sign in / Sign up

Export Citation Format

Share Document