1. Academic Validation
  2. Signaling Pathway in the Osmotic Resistance Induced by Angiotensin II AT2 Receptor Activation in Human Erythrocytes

Signaling Pathway in the Osmotic Resistance Induced by Angiotensin II AT2 Receptor Activation in Human Erythrocytes

  • Rep Biochem Mol Biol. 2021 Jul;10(2):314-326. doi: 10.52547/rbmb.10.2.314.
Camila Cristina Guimarães-Nobre 1 2 Evelyn Mendonça-Reis 1 2 Luana Passinho-da-Costa 1 3 Leandro Miranda-Alves 4 2 5 Hassan Clemilson Berto-Junior 1 4 2 3
Affiliations

Affiliations

  • 1 Grupo de Pesquisa em Fisiologia Eritróide - GPFisEri, Universidade Federal do Rio de Janeiro, Campus Macaé, Brazil.
  • 2 Programa de Pós-graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Brazil.
  • 3 Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Campus Macaé, Brazil.
  • 4 Laboratório de Endocrinologia Experimental- LEEx, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
  • 5 Programa de Pós-graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
Abstract

Background: Angiotensin II regulates blood volume via AT1 (AT1R) and AT2 (AT2R) receptors. As cell integrity is an important feature of mature erythrocyte, we sought to evaluate, in vitro, whether angiotensin II modulates resistance to hemolysis and the signaling pathway involved.

Methods: Human blood samples were collected and hemolysis assay and angiotensin II signaling pathway profiling in erythrocytes were done.

Results: Hemolysis assay created a hemolysis curve in presence of Ang II in several concentrations (10-6 M, 10-8 M, 10-10 M, 10-12 M). Angiotensin II demonstrated protective effect, both in osmotic stressed and physiological situations, by reducing hemolysis in NaCl 0.4% and 0.9%. By adding receptors antagonists (losartan, AT1R antagonist and PD 123319, AT2R antagonist) and/or signaling modulators for AMPK, Akt/PI3K, p38 and PKC we showed the protective effect was enhanced with losartan and abolished with PD 123319. Also, we showed activation of p38 as well as PI3K/Akt pathways in this system.

Conclusion: Ang II protects human erythrocytes from hypo-osmotic conditions-induced hemolysis by activating AT2 receptors and triggering intracellular pathways.

Keywords

Angiotensin II; Erythrocyte; Osmotic fragility; Signaling pathway.

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