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Cell Proteomics analysis after AT1 receptor stimulation by ligands with diferente pharmacological profiles

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Author(s):
Sarah Capelupe Simões
Total Authors: 1
Document type: Doctoral Thesis
Press: Ribeirão Preto.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
Defense date:
Examining board members:
Claudio Miguel da Costa Neto; Rosely Oliveira Godinho; Rita de Cassia Aleixo Tostes Passaglia; Felipe Roberti Teixeira
Advisor: Claudio Miguel da Costa Neto; Lucas Tabajara Parreiras e Silva
Abstract

G-protein coupled receptors (GPCRs) are important targets in biomedical studies. Angiotensin II type 1 receptor (AT1R) mediates important pathophysiological effects in different organs and tissues, where the peptide AngII is its main effector. In this work, we investigated by proteomic analysis how stimulation of HEK293T cells expressing AT1R 24hrs by the ligands AngII, TRV027, Ang1-7 or L1623,313, which have different pharmacological profiles, modulate the total abundance of proteins, and how these alterations can modify events such as apoptosis and autophagy. After the global analysis of proteins, we performed a of cellular subfractions study by standardization of cell fractionation and mass spectrometry analysis. This study, using different approaches such as choosing ligands with different pharmacological profiles and monitoring proteins enriched in different cellular subfractions, allowed the description of cellular events and signaling pathways closely related to AT1R activation. Our study significantly enriches the knowledge about AT1R, which shall allow in the future to correlate microscopic cellular events, such as protein traffic, to more complex physiological events, and hence to contribute and drive the development of new drugs. (AU)

FAPESP's process: 16/08920-0 - Comparative analysis of the AT1 receptor signaling profile after activation by balanced and biased agonists by proteomic approach
Grantee:Sarah Capelupe Simões
Support Opportunities: Scholarships in Brazil - Doctorate