Studies of radical acetylation of proteins using proteomics tools

• Grant number: 13/07763-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2013
• Effective date (End): August 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Nilson Antonio de Assunção
• Grantee: Leticia Dias Lima Jedlicka
• Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 12/50191-4 - Synthesis, kinetic studies and applications of substrates and inhibitors for proteolytic enzymes, AP.TEM

Abstract

This project aims to use bioanalytical tools in order to study the radical acetylation ofthe proteins. The superoxide anion is produced in oxidative stress and reacts with nitric oxide generating peroxynitrite which attacks the alpha carbon of the diacetyl producing radical species. These radicals are able to acetylate proteins and nitrogenous bases in vitro. The exposure to diacetyl is associated to several illnesses, mostly lung diseases. The non controlled radical acetylation may cause changes in protein functions and genetic failure which implies in diseases and mutation. The purpose of this work is to verify the radical acetylation caused by peroxinitrite/diacetyl reaction in vivo and the influence of these changes in the proteomic expression in lung tissue. It will be carried out a study using Wistar mice treated with i) inactive ingredient, ii) peroxynitrite; iii) 13C labeled diacetyl; iv) 13C labeled diacetyl and peroxynitrite. The metabolites and proteins extracted from each group will be analyzed by capillary electrophoresis, two dimensional gel electrophoresis, liquid chromatography, western blot and mass spectrometry in order to separate and identify proteins and the position of their acetylation. From these results we hope to answer some relevant biological questions proposing a non enzymatic mechanism to protein acetylation and how it is related with the proteomic expression in oxidative stress and the exposure of the diacetyl. The answers to these questions may contribute to understand the

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LIMA JEDLICKA, LETICIA DIAS; GUTERRES, SHEILA BARRETO; BALBINO, ALEKSANDRO MARTINS; NETO, GIUSEPPE BRUNO; LANDGRAF, RICHARDT GAMA; FERNANDES, LILIAM; CARRILHO, EMANUEL; HENRIQUES BECHARA, ETELVINO JOSE; ASSUNCAO, NILSON A. Increased chemical acetylation of peptides and proteins in rats after daily ingestion of diacetyl analyzed by Nano-LC-MS/MS. PeerJ, v. 6, APR 25 2018. Web of Science Citations: 2.

LIMA JEDLICKA, LETICIA DIAS; SILVA, JUCIARA DA COSTA; BALBINO, ALEKSANDRO MARTINS; NETO, GIUSEPPE BRUNO; SOUSA FURTADO, DANIELLE ZILDEANA; TORRES DA SILVA, HERON DOMINGUEZ; CORREIA CAVALCANTI, FERNANDADE BARROS; VAN DER HEIJDEN, KARIN MARIE; AVELLANEDA PENATTI, CARLOS ALBERTO; HENRIQUES BECHARA, ETELVINO JOSE; ASSUNCAO, NILSON ANTONIO. Effects of Diacetyl Flavoring Exposure in Mice Metabolism. BIOMED RESEARCH INTERNATIONAL, 2018. Web of Science Citations: 2.

SOUSA FURTADO, DANIELLE ZILDEANA; VILELA DE MOURA LEITE, FERNANDO BRUNALE; BARRETO, CLEBER NUNES; FARIA, BERNADETE; LIMA JEDLICKA, LETICIA DIAS; SILVA, ELISANGELA DE JESUS; TORRES DA SILVA, HERON DOMINGUEZ; HENRIQUES BECHARA, ETELVINO JOSE; ASSUNCAO, NILSON ANTONIO. Profiles of amino acids and biogenic amines in the plasma of Cri-du-Chat patients. Journal of Pharmaceutical and Biomedical Analysis, v. 140, p. 137-145, JUN 5 2017. Web of Science Citations: 5.