Hyperphosphatemia, Phosphoprotein Phosphatases, and Microparticle Release in Vascular Endothelial Cells

Journal of the American Society of Nephrology : JASN
Nima AbbasianAlan Bevington

Abstract

Hyperphosphatemia in patients with advanced CKD is thought to be an important contributor to cardiovascular risk, in part because of endothelial cell (EC) dysfunction induced by inorganic phosphate (Pi). Such patients also have an elevated circulating concentration of procoagulant endothelial microparticles (MPs), leading to a prothrombotic state, which may contribute to acute occlusive events. We hypothesized that hyperphosphatemia leads to MP formation from ECs through an elevation of intracellular Pi concentration, which directly inhibits phosphoprotein phosphatases, triggering a global increase in phosphorylation and cytoskeletal changes. In cultured human ECs (EAhy926), incubation with elevated extracellular Pi (2.5 mM) led to a rise in intracellular Pi concentration within 90 minutes. This was mediated by PiT1/slc20a1 Pi transporters and led to global accumulation of tyrosine- and serine/threonine-phosphorylated proteins, a marked increase in cellular Tropomyosin-3, plasma membrane blebbing, and release of 0.1- to 1-μm-diameter MPs. The effect of Pi was independent of oxidative stress or apoptosis. Similarly, global inhibition of phosphoprotein phosphatases with orthovanadate or fluoride yielded a global protein phosphory...Continue Reading

References

Sep 1, 1970·The Biochemical Journal·H F WoodsH A Krebs
Jan 1, 1984·Molecular and Cellular Biochemistry·G Szajerka, J Kwiatkowska
Jan 1, 1995·The Journal of Clinical Investigation·D P RathP M Robitaille
Dec 20, 1996·The Journal of Biological Chemistry·L Hoffman, M Rechsteiner
Jan 10, 1997·The Journal of Biological Chemistry·G HuyerC Ramachandran
Jun 23, 1998·Experimental Lung Research·M A BuzalafH Aoyama
Dec 16, 1998·Dementia and Geriatric Cognitive Disorders·R C Petersen
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Nov 25, 2004·International Journal of Cardiology·Leon Bernal-MizrachiYeon S Ahn
Oct 24, 2006·The Journal of Biological Chemistry·Yijun JinPatricia J Gallagher
Mar 6, 2007·Thrombosis and Haemostasis·Elena I SinauridzeFazoil I Ataullakhanov
Apr 4, 2008·American Journal of Physiology. Renal Physiology·G S Di MarcoH Pavenstädt
Feb 27, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Ismail DursunMetin Gurgoze
May 2, 2009·Journal of the American Society of Nephrology : JASN·Emi ShutoEiji Takeda
May 15, 2010·Thrombosis Research·Nigel S KeyJen-Yea Chang
Oct 21, 2010·Clinical Science·M Shawkat Razzaque
Oct 4, 2011·Atherosclerosis·Timothy J Ellam, Timothy J A Chico
Aug 24, 2012·Kidney International·Giovana Seno Di MarcoMarcus Brand
Aug 13, 2013·PloS One·James O BurtonNigel J Brunskill

❮ Previous
Next ❯

Citations

Feb 26, 2016·Clinical Journal of the American Society of Nephrology : CJASN·Cynthia S Ritter, Eduardo Slatopolsky
Dec 19, 2015·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Antonio Bellasi
Jun 1, 2018·Hospital Practice·Wisit CheungpasitpornStephen B Erickson
Aug 16, 2018·American Journal of Physiology. Renal Physiology·Nima AbbasianAlan Bevington
Nov 28, 2018·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jeanne BouabdallahYoussef Bennis
Apr 9, 2020·Toxins·Thomas EbertPeter Stenvinkel
Jun 25, 2020·Toxins·Regiane Stafim da CunhaAndréa Emilia Marques Stinghen
Sep 29, 2020·Frontiers in Endocrinology·Sarah BuchananPaul G Shiels
Sep 8, 2020·Platelets·Nima Abbasian, Matthew T Harper
Feb 6, 2017·PloS One·Tingting LiZiyad Al-Aly
Mar 14, 2017·BioMed Research International·Yi-Chou HouKuo-Cheng Lu
May 1, 2020·Frontiers in Cell and Developmental Biology·Hara T GeorgatzakouMarianna H Antonelou
Aug 31, 2017·Clinical Kidney Journal·Claudia YusteManuel Praga
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Andres CarmonaPedro Aljama
May 10, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Marc Vila CuencaMarc G Vervloet
May 16, 2019·Toxins·Giane FavrettoAndréa Emilia Marques Stinghen
Jul 29, 2020·Journal of Clinical Medicine·Stefanos RoumeliotisCarmine Zoccali
Oct 10, 2018·Nephrology·Yi-Chou HouKuo-Cheng Lu
Nov 4, 2020·Journal of Clinical Medicine·Nima AbbasianNigel J Brunskill
Jun 4, 2021·Frontiers in Cell and Developmental Biology·Li ZhangKristina I Boström
Jun 1, 2021·Frontiers in Physiology·Carlos Alexandre FalconiMarcela Sorelli Carneiro-Ramos

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

Diabetes & Metabolism
A S LeroyerChantal M Boulanger
Journal of Internal Medicine
A S LeroyerChantal M Boulanger
American Journal of Physiology. Renal Physiology
G S Di MarcoH Pavenstädt
Toxicological Sciences : an Official Journal of the Society of Toxicology
Se-Hwan KimJin-Ho Chung
© 2022 Meta ULC. All rights reserved