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

Evelyn Mendonça-Reis,Luana Passinho-Da-Costa,Leandro Miranda-Alves,Camila Cristina Guimarães-Nobre,Clemilson Berto-Junior

doi:10.52547/rbmb.10.2.314

Evelyn Mendonça-Reis, Luana Passinho-Da-Costa + Show 3 more

Open Access

https://doi.org/10.52547/rbmb.10.2.314

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Abstract

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. Human blood samples were collected and hemolysis assay and angiotensin II signaling pathway profiling in erythrocytes were done. 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. Ang II protects human erythrocytes from hypo-osmotic conditions-induced hemolysis by activating AT2 receptors and triggering intracellular pathways.

Highlights

Angiotensin II (Ang II) is an octapeptide belonging to renin-angiotensin-aldosterone system (RAS) and is responsible for ubiquitous actions in several tissues
Stimulated AT1R is described as an activator of diverse signaling pathways among several cell types: Gao and co- workers showed activation of ERK 1/2 and p38 MAPK pathways when AT1R is activated in rat heart [5]; in MCF-7 breast cancer cells, AT1R activates PI3-kinase/Akt pathway prompting survival [6]; Ang II stimulates AMPActivated Protein Kinase (AMPK), inducing inflammation in atrial myocytes [7]
Peng et al (2019) found erythrocyte AMPK as a missing link that promotes oxygen delivery by hemoglobin in a helpful way to prevent and counteract kidney diseases promoted by hypoxia, bringing an interesting new target for treating the disease; this AMPK activation occurred through erythrocyte adenosine surface receptor ADORA2B [21]

Summary

Introduction

Angiotensin II (Ang II) is an octapeptide belonging to renin-angiotensin-aldosterone system (RAS) and is responsible for ubiquitous actions in several tissues. Effects observed with Ang II occur by its binding in one of the two well-recognized receptors named AT1R and AT2R with well-known signaling pathways [1]. Methods: Human blood samples were collected and hemolysis assay and angiotensin II signaling pathway profiling in erythrocytes were done. 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. Conclusions: Ang II protects human erythrocytes from hypo-osmotic conditions-induced hemolysis by activating AT2 receptors and triggering intracellular pathways

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