Startseite Lebenswissenschaften Role of protein tyrosine phosphatase 1B (PTP1B) in the increased sensitivity of endothelial cells to a promigratory effect of erythropoietin in an inflammatory environment
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Role of protein tyrosine phosphatase 1B (PTP1B) in the increased sensitivity of endothelial cells to a promigratory effect of erythropoietin in an inflammatory environment

  • María Eugenia Chamorro ORCID logo EMAIL logo , Romina Maltaneri , Agustina Schiappacasse , Alcira Nesse und Daniela Vittori
Veröffentlicht/Copyright: 16. Juli 2020
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 401 Heft 10

Abstract

The proliferation and migration of endothelial cells are vascular events of inflammation, a process which can also potentiate the effects of promigratory factors. With the aim of investigating possible modifications in the activity of erythropoietin (Epo) in an inflammatory environment, we found that Epo at a non-promigratory concentration was capable of stimulating EA.hy926 endothelial cell migration when TNF-α was present. VCAM-1 and ICAM-1 expression, as well as adhesion of monocytic THP-1 cells to endothelial layers were also increased. Structurally modified Epo (carbamylation or N-homocysteinylation) did not exhibit these effects. The sensitizing effect of TNF-α on Epo activity was mediated by the Epo receptor. Inhibition assays targeting the PI3K/mTOR/NF-κB pathway, shared by Epo and TNF-α, show a cross-talk between both cytokines. As observed in assays using antioxidants, cell migration elicited by TNF-α + Epo depended on TNF-α-generated reactive oxygen species (ROS). ROS-mediated inactivation of protein tyrosine phosphatase 1B (PTP1B), involved in Epo signaling termination, could explain the synergistic effect of these cytokines. Our results suggest that ROS generated by inflammation inactivate PTP1B, causing the Epo signal to last longer. This mechanism, along with the cross-talk between both cytokines, could explain the sensitizing action of TNF-α on the migratory effect of Epo.

Keywords: cytokine receptors; endothelial cells; erythropoietin; protein tyrosine phosphatase 1B; reactive oxygen species; tumor necrosis factor α
Corresponding author: María Eugenia Chamorro, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto del Departamento de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Ciudad Autónoma deBuenos Aires, C1428EHA, Argentina, E-mail:
María Eugenia Chamorro and Romina Maltaneri: These authors contributed equally to this work.

Funding source: Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT), Argentina

Funding source: Universidad de Buenos Aires, Argentina

Funding source: Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina

Acknowledgments

This work was supported by grants from the Universidad de Buenos Aires (UBACYT), the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and the Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT). The authors are grateful to Zelltek S.A. (Argentina) for supplying human recombinant erythropoietin. Dr. Alcira Nesse, Dr. Daniela Vittori and Dr. María Eugenia Chamorro are research scientists at the CONICET, and Dr. Romina Maltaneri and Lic. Agustina Schiappacasse have received fellowships from the CONICET (Argentina).

  1. Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This research was funded by the Universidad de Buenos Aires (UBACYT), the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and the Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT).

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Conflict of interest statement: The authors declare that they have no existing conflicts of interest regarding this article.

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Received: 2020-02-14
Accepted: 2020-05-04
Published Online: 2020-07-16
Published in Print: 2020-09-25

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hsz-2020-0136
Schlagwörter für diesen Artikel
cytokine receptors; endothelial cells; erythropoietin; protein tyrosine phosphatase 1B; reactive oxygen species; tumor necrosis factor α

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Small dense low-density lipoprotein-lowering agents
  4. The piRNA pathway in planarian flatworms: new model, new insights
  5. Research Articles
  6. Anti-amyloidogenic effect of artemin on α-synuclein
  7. Galectin-3 is modulated in pancreatic cancer cells under hypoxia and nutrient deprivation
  8. Role of protein tyrosine phosphatase 1B (PTP1B) in the increased sensitivity of endothelial cells to a promigratory effect of erythropoietin in an inflammatory environment
  9. Effects of extracellular Hsp70, lipopolysaccharide and lipoteichoic acid on human monocyte-derived macrophages and differentiated THP-1 cells
  10. High-mobility group box 3 (HMGB3) silencing inhibits non-small cell lung cancer development through regulating Wnt/β-catenin pathway
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