Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction

Burnstock, Geoffrey

doi:10.1046/j.1469-7580.1999.19430335.x

Cited by 326 publications

(252 citation statements)

References 80 publications

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“…Here, we show that both AA and ETYA induce cell proliferation in BTECs in accordance with a role for the fatty acid both in normal and tumor-derived endothelial cells. Interestingly, B-TEC proliferation is also significantly enhanced by ATP application; even if ATP has been shown to be mainly implicated in the control of short-term events associated with the control of vascular tone (41), different studies suggest a role for ATP in long-term vascular events (such as cell proliferation in different endothelial cell types; refs. 42,43).…”

Section: Discussionmentioning

confidence: 99%

Arachidonic Acid–Induced Ca2+ Entry Is Involved in Early Steps of Tumor Angiogenesis

Fiorio

Grange

Antoniotti

et al. 2008

Molecular Cancer Research

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Growth factor -induced intracellular calcium signals in endothelial cells regulate cytosolic and nuclear events involved in the angiogenic process. Among the intracellular messengers released after proangiogenic stimulation, arachidonic acid (AA) plays a key role and its effects are strictly related to calcium homeostasis and cell proliferation. Here, we studied AA-induced intracellular calcium signals in endothelial cells derived from human breast carcinomas (B-TEC). AA promotes B-TEC proliferation and organization of vessel-like structures in vitro. The effect is directly mediated by the fatty acid without a significant contribution of its metabolites. AA induces Ca 2+ i signals in the entire capillary-like structure during the early phases of tubulogenesis in vitro. No such responses are detectable in B-TECs organized in more structured tubules. In B-TECs growing in monolayer, AA induces two different signals: a Ca 2+ i increase due to Ca 2+ entry and an inhibition of store-dependent Ca 2+ entry induced by thapsigargin or ATP. An inhibitor of Ca 2+ entry and angiogenesis, carboxyamidotriazole, significantly and specifically decreases AA-induced B-TEC tubulogenesis, as well as AA-induced Ca 2+ signals in B-TECs. We conclude that (a) AA-activated Ca 2+ entry is associated with the progression through the early phases of angiogenesis, mainly involving proliferation and tubulogenesis, and it is down-regulated during the reorganization of tumor-derived endothelial cells in capillary-like structures; and (b) inhibition of AA-induced Ca 2+ entry may contribute to the antiangiogenic action of carboxyamidotriazole. (Mol Cancer Res 2008;6(4):535 -45)

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Section: Discussionmentioning

confidence: 99%

Arachidonic Acid–Induced Ca2+ Entry Is Involved in Early Steps of Tumor Angiogenesis

Fiorio

Grange

Antoniotti

et al. 2008

Molecular Cancer Research

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“…It has been shown that P2 activation leads to increases in concentration of intracellular calcium and PGE2 release (Naemsch et al, 2001). ATP, which activates this pathway, is typically released by bone, endothelial and epithelial cells and fibroblasts under stress conditions, acting as a DAMP/alarmin (Bodin & Burnstock, 1998;Burnstock, 1999;Furuya, Sokabe & Furuya, 2005;Grygorczyk & Hanrahan, 1997;John & Barakat, 2001;Katsuragi & Migita, 2004;Katz, Boland & Santillan, 2006;Kerkweg & de Groot, 2005;Milner et al, 1992;Milner et al, 1990b;Ohata et al, 1997;Patel et al, 2005;Romanello et al, 2001;Sauer, Hescheler & Wartenberg, 2000;Yamamoto et al, 2003).…”

Section: P2x7 Receptor: a Possible Mediator Of Orthodontic Mechanotramentioning

confidence: 99%

Orthodontic mechanotransduction and the role of the P2X7 receptor

Viecilli

Katona

Chen

et al. 2009

American Journal of Orthodontics and Dentofacial Orthopedics

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DEDICATIONTo my parents, who have supported my education. iv ACKNOWLEDGMENTSOne of the most important things I have learned during my PhD is the necessity of the existence of a working network of people that can help you achieve your goals. The more effectively this network functions, the higher the chance you will achieve the goals quickly.I would first like to thank my parents, who have unconditionally supported my decision to abandon a profitable private practice in Orthodontics, and return to humble student conditions while aiming for a full time academic career.I also thank my girlfriend Laura Kruter who has (almost always) been ok with my, some might say, not very sane ideas. Sometimes they do turn out fine, though (like this "PhD" one).I can hardly think of anyone else that could have complemented my work and ideas during this Program as well as Dr. Thomas Katona. While I was passionately conditioned to an idea, he was always rational and careful. While I was sometimes furious with a shortcoming, he was always temperate and humorous. When I ran into his office with some news about a project, he would always listen and almost never seem too busy to see me. While I was working and something went wrong, he would listen and wonder with me about the "whys" and "hows", instead of telling me what to do or express disappointment. He was even subject to some of my home culinary experiments. I was extremely fortunate to find someone that thought about science the same way I did, and that actually helped me with my project instead of just telling me what to do. I felt like we worked as a team, and that helped to increase my motivation during my studies. The third part of this project tested the role of the P2X7 receptor in the dentoalveolar morphology of C57B/6 mice. P2X7R KO (knockout) mice were compared to C57B/6 WT to identify differences in a maxillary molar and bone. Tooth dimensions viii were measured and 3D bone morphometry was conducted. No statistically significant differences were found between the two mouse types. P2X7R does not have a major effect on alveolar bone or tooth morphology.The final part examines the role of the P2X7 receptor in a controlled biomechanical model. Orthodontic mechanotransduction was compared in wild-type (WT) and P2X7R knock-out (KO) mice. Using Finite Element Analysis, mouse mechanics were scaled to produce typical human stress levels. Relationships between the biological responses and the calculated stresses were statistically tested and compared.There were direct relationships between certain stress magnitudes and root resorption and bone formation. Hyalinization and root and bone resorption were different in WT and KO. Orthodontic responses are related to the principal stress patterns in the PDL and the P2X7 receptor plays a significant role in their mechanotransduction.

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“…Shear stress and hypoxia are important stimuli of both ATP and UTP release from endothelial cells [78]. The P2X 4 receptor is the highest expressed P2 receptor in endothelium [79,80].…”

Section: Direction and Mechanism Of The Endothelial Flow Responsementioning

confidence: 99%

The touching story of purinergic signaling in epithelial and endothelial cells

Öhman

Erlinge

2012

Purinergic Signalling

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Endothelial and epithelial cells have something in commonthey are both the barrier and bridge between different environments. Forming a one-cell layer lining of blood vessels, airways, and urinary tract, they are in constant contact with a wide variety of cells, putting high demands on the communication skills of these cells. The purinergic signaling system offers a dynamic and versatile way for local and rapid intercellular communication and involves three processes: nucleotide release, enzymatic degradation, and activation of purinergic receptors. With an impressive number of molecular members of the system (15 P2 receptor subtypes and in total 16 nucleotide-degrading enzymes), cells have managed to put purines and pyrimidines as well as their derivatives to use in an array of different areas, including regulation of flow, secretion, and vascular tone. Indeed, the purinergic signaling system is an ancient way of intercellular communication that most likely could be found in the first most primitive life form [1]. The scope of this review is to give an overview of exciting features of purinergic signaling and examples of gaps to fill in understanding its role in the cells lining the body-the endothelium and the epithelium. Purinergic signaling-an overviewExtracellular nucleotides exert their paracrine signaling by binding to P2 receptors present at the cell surface. The P2 receptor family is divided into two groups: P2X receptors, which are ligand-activated ion channels, and P2Y receptors, which are G protein-coupled receptors (reviewed in [2]). Each receptor is characterized by its affinity pattern for different nucleotides and different cell types display varying receptor profiles. While P2X receptors respond only to ATP, P2Y receptors can be activated by other nucleotides such as ADP, UTP, and UDP. Extracellular nucleotide concentrations are precisely regulated by ecto-enzymes, which cleave nucleotide tri-/diphosphates. The result of signaling by the extracellular nucleotides ATP/ADP, UTP/UDP and the nucleoside adenosine is both acute, for example the rapid platelet aggregation induced by ADP, and chronic, via changes in gene expression induced by P2 receptor stimulation. Ligand availability for P2 receptors is regulated by a group of enzymes termed ectonucleotidases. NTPDase1 (apyrase; CD39) cleaves ATP to AMP, NTPDase2 (CD39L1) cleaves ATP to ADP, and 5′-ectonucleotidase (CD73) generates adenosine from AMP. Adenosine is the end product of purinergic signaling, acting on adenosine receptors (A1, A2a, A2b, and A3; also termed P1 receptors) or recycling by the cell after reuptake through the equilibrating nucleoside transporters ENT1 and 2. UTP is believed to be released simultaneously with ATP via the same mechanism but at a lower concentration (UTP/ATP, 1:10-100). UTP is degraded in the same way as ATP, but the biological function of uridine is poorly understood and no uridine receptor has been identified. Figure 1 shows an outline of nucleotide metabolism. Purinergic toneAll investigators that have tried t...

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Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction

Cited by 326 publications

References 80 publications

Arachidonic Acid–Induced Ca2+ Entry Is Involved in Early Steps of Tumor Angiogenesis

Arachidonic Acid–Induced Ca2+ Entry Is Involved in Early Steps of Tumor Angiogenesis

Orthodontic mechanotransduction and the role of the P2X7 receptor

The touching story of purinergic signaling in epithelial and endothelial cells

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