AGH is a new hemoglobin alpha-chain fragment with antinociceptive activity.

Author(s)

Natália Mazini Ribeiro

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2013-05-13

Examining board members

Emer Suavinho Ferro; Vitor Marcelo Silveira Bueno Brandão de Oliveira; Rosana de Lima Pagano; Fernanda Calheta Vieira Portaro; Andréa da Silva Torrão

• Advisor: Emer Suavinho Ferro; Vanessa Rioli

Abstract

Limited proteolysis of certain proteins leads to the release of endogenous opioid peptides. Several reports have shown that hemoglobin-derived peptides such as hemorphins and hemopressins have an antinociceptive effect by modulating GPCR activity. In the present study, a substrate capture assay (SCA) was combined with isotopic labeling and LC-MS/MS to identify and characterize a new bioactive hemoglobin fragment that binds to EP24.15. AGH, a new peptide identified in this work, inhibits peripheral hyperalgesic responses through <font face=\"Symbol\">m opioid receptors (MOR). The persistence of AGH peptide in perfused nervous tissue suggests its physiological relevance. Although AGH is derived from hemoglobin and it is a peptide with opioid activity, it lacks the key sequence of hemorphins (YPWT), indicating that it is part of a new class of peptides derived from hemoglobin. Additionally, the AGH modulates interactions between 14-3-3<font face=\"Symbol\">e and EP24.15 proteins in vitro and may be related to the unconventional EP24.15 secretion. (AU)

• FAPESP's process: 10/01453-0 - IDENTIFICATION OF NEW ENDOGENOUS PEPTIDES WITH POTENTIAL THERAPEUTIC FUNCTIONS BY USING CATALYTICALLY INACTIVE FORMS OF ENZYMES EP 24.15 AND EP 25.16
• Grantee: Natalia Mazini Ribeiro
• Support Opportunities: Scholarships in Brazil - Doctorate