Laboratory of Oxidants and Radical Biochemistry and EPR









 Examples of radicals detected by the group.

 


Prof. Dr. Ohara Augusto

-Professor of Biochemistry; Member of the Brazilian Academy of Sciences, 2002; International EPR Society Medal, 2002; Order of Scientific Merit, 2006; Scopus Prize, 2009; TWAS Member, 2011.

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RESEARCH INTERESTS

Our group has always been focused in understanding the molecular mechanisms by which radicals and oxidants mediate biological responses that range from signaling circuits involved in physiology and pathophysiology to cellular and tissue injury. By the use of electron paramagnetic resonance (EPR) and kinetics, among other experimental approaches, we have contributed to the characterization of novel reactive  species, such as alkyl/aryl radicals (R●/Ar●),  peroxynitrite (ONOO-), peroxymonocarbonate (HCO4-) and carbonate radical (CO3●-), as well as of their biological sources and fates. By studying the reactivity of radicals and oxidants with potential biological targets in vitro and in vivo, we aim to continue contributing to advance the field of redox biology. We concur with the view that further advances require interdisciplinary approaches combining system biology with rigorous chemical and biological studies.   


Connecting the chemical and biological properties of nitric oxide. From Toledo Jr and Augusto, Chem. Res. Toxicol. 25, 975, 2012. Copyright American Chemical Society.

Openings for pos-docs and graduate students. 


CURRENT RESEARCH

 


Presently, we are addressing the following problems.

i) The redox properties of the main physiological buffer, the pair bicarbonate/carbon dioxide. In addition to contribute to the understanding and control of numerous pathophysiological states and clinical conditions (for instance, emphysema, respiratory muscle paralysis, pulmonary fibrosis), these studies may impact our view on how increased levels of atmospheric carbon dioxide may affect life on Earth.

ii) The structural and mechanistic properties of the human enzyme superoxide dismutase1 that modulate its pro-oxidant and pro-aggregating properties. It is expected that these studies will contribute to the elucidation of pathogenic mechanisms underlying neurodegenerative diseases, in particular those involved in amyotrophic lateral sclerosis.

Production of the carbonate radical during the peroxidase activity of SOD1 leading to protein oxidation and, eventually,
oligomerization and aggregation. From Medinas et al, IUBM Life, 2007;
Chem Res Toxicol, 2009 and Free Radic Biol Med, 2010.

 









iii) The mechanisms by which cyclic nitroxides are protective against oxidative and nitro-oxidative damage in vitro and in experimental animals. In our view these studies are relevant because nitroxides may provide new antioxidant and anti-inflammatory strategies.




Mechanisms by which the cyclic nitroxide tempol can attenuate inflammatory injury. From Augusto et al, An Acd. Bras. Cienc, 2008; Vaz and Augusto, Proc. Natl Acad Sci USA, 2009; Queiroz et al, Biochem. J. 2011.



iv) The kinetics of the reactions of proteins (heme proteins, thiol proteins, etc) with oxidants and radicals. These studies are still limited in the literature but are useful to unravel the physiological and pathophysiological roles of species that are elusive under biological conditions as oxidants and radicals are. (For a review see, Toledo Jr e Augusto, Chem Res Toxicol  25, 975, 2012).

 


Openings for pos-docs and graduate  students. 




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PUBLICATIONS

Total publications (up to May 2012):

-116 articles in peer-reviewed journals;

-11 book chapters;

-1 book (Portuguese).

-h index= 34 (webofscience, May 2012).


Selected articles

     
 

         Augusto, O., Bonini, M. G., Amanso, A. M., Linares, E., Santos, C. C. X. and de Menezes, S. L. (2002) Nitrogen dioxide and carbonate radical anion: two emerging radicals in Biology. Free Radic. Biol. Med. 32, 841-859.

         Bonini, M. G., Radi, R., Ferrer-Sueta, G., da- Costa Ferreira, A. M. and Augusto, O. (1999) Direct detection of the carbonate radical anion produced from peroxynitrite and carbon dioxide. J. Biol. Chem. 274, 10802-1086.

         Augusto, O., Beilan, H.  S. and Ortiz de Montellano, P. R. (1982) The catalytic mechanism of cytochrome P450. Spin trapping evidence for one-electron substrate oxidation. J. Biol. Chem. 257, 11288-11295.

         Augusto, O.,  Kunze, K. L. and Ortiz de Montellano, P. R. (1982) N-phenyl protoporphyrin IX. Formation in the hemoglobin-phenylhydrazine reaction: evidence for a protein-stabilized iron phenyl intermediate. J. Biol. Chem., 257, 6231-6241.

         Quijano, C., Alvarez, B., Gatti, R. M., Augusto, O. and Radi, R. (1997) Pathways of peroxynitrite oxidation of thiol groups. Biochem. J. 322, 167-173.

         Augusto, O., Gatti, R.M. and Radi, R. (1994) Spin-trapping studies of peroxynitrite decomposition and of 3-morpholinosydnomine N-ethylcarbamide auto-oxidation. Arch. Biochem. Biophys. 310, 118-125.

         Gatti, R. M., Radi, R. and Augusto, O. (1994) Peroxynitrite-mediated oxidation of albumin to the protein thiyl free radical. FEBS Letters  348, 287-290.

         Laurindo, F. R. M., Pedro, M. A., Barbeiro, H. V., Carvalho, M. H. C., Augusto, O. and da-Luz, P. (1994) Vascular free radical release. Ex vivo and in vivo evidence for a flow-dependent endothelial mechanism. Circ. Res. 74, 700-709.

         Santos, C. X. C., Anjos, E. I. and Augusto, O. (1999) Uric acid oxidation by peroxynitrite: multiple reactions, free radical formation and amplification of lipid oxidation. Arch. Biochem. Biophys. 372, 285-294.

         Bonini, M. G. and Augusto, O. (2001) Carbon dioxide stimulates the production of thiyl, sulfinyl, and dissulfide radical anion from thiol oxidation by peroxynitrite. J.Biol. Chem. 276, 9749-9754.


FINANCIAL SUPPORT

  

                                                                                     




http://www2.iq.usp.br/redoxoma/