USP
Universidade de São Paulo

Etelvino José Henriques Bechara

Professor Sênior - Departamento de Bioquímica
ESTRESSE OXIDATIVO EM DESORDENS METABÓLICAS
3091-3869 
 ebechara@iq.usp.br

Resumo

Estudamos metabólitos geradores de radicais livres (alfa-aminocetonas, alfa-oxoaldeidos, peroxinitrito) e de outros intermediários reativos (peróxidos orgânicos, espécies tripletes, oxigênio singlete) acumulados em desordens inatas (diabetes, porfiria aguda intermitente, cetoacidoses) e adquiridas (plumbismo). Nosso propósito é elucidar mecanismos de reação destes compostos, acoplados a danos oxidativos a biomoléculas (proteínas e DNA), organelas (mitocondrias), culturas celulares e tecidos (fígado, cérebro). Hoje focalizamos a atividade prooxidante e alquilante de aminoacetona, ácido 5-aminolevulínico, 1,4-diamino-2-butanona, derivados de glioxal,  aldeídos alfa-beta insaturados, beta-dicetonas e hidrazidas. Utilizamos principalmente técnicas de cinética rápida, quimioluminescência, ressonância paramagnética de spin, eletroforese capilar e espectroscopia de massas.

 

Summary

We study the mechanisms of aerobic oxidation of various metabolites of medical interest (alpha-aminoketones, alpha-oxoaldehydes, peroxynitrite), via free radical, organic peroxide intermediates, and electronically excited species (triplet carbonyls and singlet oxygen), and their noxious action on biomolecules (proteins and DNA), cell structures (mitochondria), cell cultures, and tissues (liver, brain). We are particularly interested in metabolic disorders triggered by 5-aminolevulinic acid (hepatic porphyria, lead poisoning), succinylacetone (tyrosinosis), aminoacetone (diabetes) known to be accumulated in blood and other tissues of tisues, as well as 1,4-diamino-2-butanone, a wide spectrum microbicide. Treatment of diacetyl and methylglyoxal with peroxynitrite were shown to yield acetyl radicals capable of acetylating amino acids and peptides, whereas glyoxal produced excited oxygen. Stopped flow kinetics, chemiluminescence, EPR, capillary electrophoresis, and mass spectroscopy have been routinely used in our laboratory for collecting experimental data.

 

Produção acadêmica

Curriculo (Sistema Lattes - CNPq)

Curriculo (Sistema Researcher-ID)

 

1. Olympio KPK, Oliveira PV, Naozuka J, Cardoso MRA, Marques AF, Günther WMR, Bechara EJH (2010) Surface enamel lead levels and antisocial behavior in Brazilian adolescents. Neurotoxicol. Teratol. 32, 273-279.

2. Massari J, Tokikawa R, Zanolli L, Tavares MFM, Assunção NA, Bechara EJH (2010) Acetyl radical production by the methylglyoxal/peroxynitrite system: A possible route for lysine acetylation. Chem. Res. Toxicol. 23, 1762-1770.

3. Soares CO, Alves MJM, Bechara EJH (2011) 1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation. Free Radic. Biol. Med. 50, 1760-1770.

4. Ganini D, Christoff M, Ehrenshaf M, Kadiiska MPB, Mason RP, Bechara EJH (2011) Myoglobin-H2O2 catalyzes the oxidation of β-ketoacids to α-dicarbonyls: Mechanism and implications in ketosis. Free Radic. Biol. Med. 51, 733-743.

5. Massari J, Tokikawa R, Medinas DB, Angeli JP, Di Mascio P, Assunção NA, Bechara EJH (2011). Generation of Singlet Molecular Oxygen by the Glyoxal-Peroxynitrite System. J. Am. Chem. Soc. 133, 20761-20768.

6. Soares CO, Colli W, Bechara EJH, Alves MJM (2012). 1,4-Diamino-2-butanone, a putrescine analogue, promotes redox imbalance in Trypanosoma cruzi and mammalian cells. Arch. Biochem. Biophys. 528 103–110.