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Mapping adducts generated by endogenous and exogenous aldehydes: use as biomarkers of redox stress


Several processes including oxidative metabolism, inflammation, exposure to physical agents such as UV light and ionizing radiation produce reactive intermediates capable of producing damage to biomolecules. The increase in these lesions has been linked with a variety of diseases as cancer and aging. In recent years there has been a major advance in available technology, especially mass spectrometry, allowing ultra-sensitive quantitative studies of changes in DNA, proteins and other biomolecules. This breakthrough has generated a large research effort focused on identifying the mechanisms of formation, interaction and consumption of reactive intermediates. This project aims to study the mechanisms of damage to biomolecules caused by endogenous and exogenous reactive aldehydes using modern and ultra-sensitive technology. Studies with cells and transgenic animal model for amyotrophic lateral sclerosis will be conducted as well as damage to biomolecules caused by exogenous aldehydes generated by urban pollution and cigarette smoke in vitro, animal models and human blood and urine. Several modifications to biomolecules are often formed in human tissues after exposure to reactive aldehydes, a systematic investigation of these lesions is needed to identify which lesion is the most critical in each of the situations studied. A methodology to quantify multiple lesions in DNA and glutathione, route of detoxification of these aldehydes, using HPLC /MS /MS will be performed. We emphasize that our laboratory has different standards of nucleosides and glutathione modified by aldehydes, characterized, in recent years, by our group and others. A systematic quantification of these lesions can provide important information about the pathophysiological role of these aldehydes as well as identifying potential markers of redox stress in vivo. (AU)

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Scientific publications (4)
(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)
GHOGARE, ASHWINI A.; DEBAZ, CIRO J.; OLIVEIRA, MARILENE SILVA; ABRAMOVA, INNA; MOHAPATRA, PRABHU P.; KWON, KITAE; GREER, EDYTA M.; PRADO, FERNANDA MANSO; VALERIO, HELLEN PAULA; DI MASCIO, PAOLO; GREER, ALEXANDER. Experimental and DFT Computational Insight into Nitrosamine Photochemistry-Oxygen Matters. Journal of Physical Chemistry A, v. 121, n. 32, p. 5954-5966, AUG 17 2017. Web of Science Citations: 3.
DI MASCIO, PAOLO; MARTINEZ, GLAUCIA R.; MIYAMOTO, SAYURI; RONSEIN, GRAZIELLA E.; MEDEIROS, MARISA H. G.; CADET, JEAN. Singlet molecular oxygen: Dusseldorf - Sao Paulo, the Brazilian connection. Archives of Biochemistry and Biophysics, v. 595, n. SI, p. 161-175, APR 2 2016. Web of Science Citations: 6.
BISPO, VANDERSON S.; DE ARRUDA CAMPOS, IVAN P.; DI MASCIO, PAOLO; MEDEIROS, MARISA H. G. Structural Elucidation of a Carnosine-Acrolein Adduct and its Quantification in Human Urine Samples. SCIENTIFIC REPORTS, v. 6, JAN 19 2016. Web of Science Citations: 10.
BELTRAN-GARCIA, MIGUEL J.; WHITE, JR., JAMES F.; PRADO, FERNANDA M.; PRIETO, KATIA R.; YAMAGUCHI, LYDIA F.; TORRES, MONICA S.; KATO, MASSUO J.; MEDEIROS, MARISA H. G.; DI MASCIO, PAOLO. Nitrogen acquisition in Agave tequilana from degradation of endophytic bacteria. SCIENTIFIC REPORTS, v. 4, NOV 6 2014. Web of Science Citations: 17.

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