Abstract
Oxygen and nitric oxide are known to act normally as metabolic partners in biological events and any imbalance in this cooperative relationship results in oxidative and nitrosative damage to biomolecules and organelles, threatening the cell's life. Our research proposal focuses on the pro-oxidative and acylation properties of amino acid metabolites, particularly a-aminocarbonyls and B-ketoacids that accumulate in the tissues of individuals carrying metabolic errors. We aim to study: (i) 5-aminolevulinic acid (ALA), a heme precursor elevated in intermittent acute porphyria and lead poisoning; (ii) aminoacetone (AA), a threonine and glycine catabolite accumulated in diabetes, threoninemia, and cri-du-chat; (iv) succinylacetone, a B-diketone produced at high levels from tyrosine in tyrosinosis, where it leads indirectly to ALA overload; and (iv) 2- methylacetoacetate (MAA), an isoleucine catabolite abundant in isoleucinemia carriers. These metabolites undergo aerobic oxidation yielding cytotoxic and genotoxic species such as radicals, peroxides, triplet species and a-oxoaldehydes. The the latter compounds encompass 4,5-dioxovaleric acid (DOVA), linked to ALA and SA accumulation, and methylglyoxal (MG), derived from AA and SA. In the next four years we plan to continue investigating the chemical mechanisms of ALA, AA, SA, and MA oxidation in aerated medium, triggered by metals, peroxynitrite, hemeprotein/H2O2 or hypochloride, as well as the damaging effects of their intermediates and final products - DOVA, MG, and biacetyl - on cell cultures, rats and humans. In parallel, we will developed analytical methods by CE/MS/MS for detecting these metabolites in biological samples and other biomarkers of carbonyl stress. (AU)
Scientific publications
(15)
(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)
KANESHIRO OLYMPIO, KELLY POLIDO;
GONZALEZ HUILA, MANUEL FERNANDO;
BALDINI CARDOSO, CRISTIANE DE ALMEIDA;
SACONE DA SILVA FERREIRA, ANA PAULA;
ORTIZ, ADRIELLY GARCIA;
TOMA, HENRIQUE EISI;
ALVES DA SILVA, RICARDO HENRIQUE;
LUZ, MACIEL SANTOS;
ALVES CARDOSO, MARIA REGINA;
RODRIGUES KELMER, GISLAYNE APARECIDA;
DE OLIVEIRA, PEDRO VITORIANO;
HENRIQUES BECHARA, ETELVINO JOSE;
RISSO GUNTHER, WANDA MARIA;
RABELO BUZALAF, MARILIA AFONSO.
Can in vivo surface dental enamelmicrobiopsies be used to measure remote lead exposure?.
Environmental Science and Pollution Research,
v. 25,
n. 10, SI,
p. 9322-9329,
APR 2018.
Web of Science Citations: 1.
BAADER, WILHELM J.;
STEVANI, CASSIUS V.;
BECHARA, ETELVINO J. H.
``Photo{''} Chemistry Without Light?.
Journal of the Brazilian Chemical Society,
v. 26,
n. 12,
p. 2430-2447,
DEC 2015.
Web of Science Citations: 8.
PREMI, SANJAY;
WALLISCH, SILVIA;
MANO, CAMILA M.;
WEINER, ADAM B.;
BACCHIOCCHI, ANTONELLA;
WAKAMATSU, KAZUMASA;
BECHARA, ETELVINO J. H.;
HALABAN, RUTH;
DOUKI, THIERRY;
BRASH, DOUGLAS E.
Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure.
Science,
v. 347,
n. 6224,
p. 842-847,
FEB 20 2015.
Web of Science Citations: 149.
WILHELM J. BAADER;
CASSIUS V. STEVANI;
ETELVINO J. H. BECHARA.
"Photo" Chemistry Without Light?.
Journal of the Brazilian Chemical Society,
v. 26,
n. 12,
p. -,
Dez. 2015.
MANO, CAMILA M.;
PRADO, FERNANDA M.;
MASSARI, JULIO;
RONSEIN, GRAZIELLA E.;
MARTINEZ, GLAUCIA R.;
MIYAMOTO, SAYURI;
CADET, JEAN;
SIES, HELMUT;
MEDEIROS, MARISA H. G.;
BECHARA, ETELVINO J. H.;
DI MASCIO, PAOLO.
Excited singlet molecular O-2 ((1)Delta g) is generated enzymatically from excited carbonyls in the dark.
SCIENTIFIC REPORTS,
v. 4,
AUG 4 2014.
Web of Science Citations: 25.
DE OLIVEIRA, TIAGO FRANCO;
MEDEIROS DA SILVA, AMANDA LUCILA;
DE MOURA, RAFAELA ALVES;
BAGATTINI, RAQUEL;
FALCAO DE OLIVEIRA, ANTONIO ANAX;
GENNARI DE MEDEIROS, MARISA HELENA;
DI MASCIO, PAOLO;
DE ARRUDA CAMPOS, IVAN PERSIO;
BARRETTO, FABIANO PRADO;
HENRIQUES BECHARA, ETELVINO JOSE;
DE MELO LOUREIRO, ANA PAULA.
Luminescent threat: toxicity of light stick attractors used in pelagic fishery.
SCIENTIFIC REPORTS,
v. 4,
JUN 19 2014.
Web of Science Citations: 6.
BELTRAN-GARCIA, MIGUEL J.;
PRADO, FERNANDA M.;
OLIVEIRA, MARILENE S.;
ORTIZ-MENDOZA, DAVID;
SCALFO, ALEXSANDRA C.;
PESSOA, JR., ADALBERTO;
MEDEIROS, MARISA H. G.;
WHITE, JAMES F.;
DI MASCIO, PAOLO.
Singlet Molecular Oxygen Generation by Light-Activated DHN-Melanin of the Fungal Pathogen Mycosphaerella fijiensis in Black Sigatoka Disease of Bananas.
PLoS One,
v. 9,
n. 3
MAR 19 2014.
Web of Science Citations: 24.
OLYMPIO, KELLY P. K.;
OLIVEIRA, PEDRO V.;
NAOZUKA, JULIANA;
CARDOSO, MARIA R. A.;
MARQUES, ANTONIO F.;
GUENTHER, WANDA M. R.;
BECHARA, ETELVINO J. H.
Surface dental enamel lead levels and antisocial behavior in Brazilian adolescents.
NEUROTOXICOLOGY AND TERATOLOGY,
v. 32,
n. 2,
p. 273-279,
MAR-APR 2010.
Web of Science Citations: 28.
KANESHIRO OLYMPIO, KELLY POLIDO;
NAOZUKA, JULIANA;
MAGALHAES, ANA CAROLINA;
DE PERA GARCIA, MANUEL VALENTIM;
DE OLIVEIRA, PEDRO VITORIANO;
RABELO BUZALAF, MARILIA AFONSO;
HENRIQUES BECHARA, ETELVINO JOSE;
RISSO GUENTHER, WANDA MARIA.
Microbiopsies of Surface Dental Enamel as a Tool to Measure Body Lead Burden.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES,
v. 73,
n. 9,
p. 627-636,
2010.
Web of Science Citations: 2.