Mechanisms and pathophysiological consequences of redox process. Emphasis in processes mediated by bicarbonate buffer, superoxide dismutase 1, thiol proteins and nitroxides

• Grant number: 07/54541-1
• Support Opportunities: Research Projects - Thematic Grants
• Duration: April 01, 2008 - September 30, 2012
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Ohara Augusto
• Grantee: Ohara Augusto
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Currently, free radicals and oxidants are considered to mediate responses that range from signaling circuits involved in physiology and pathology to cellular and tissue injury. It is widely conceded that the elucidation of these many inter-related processes requires a better understanding of cellular oxidative mechanisms, including the identification of involved oxidants, the pathways regulating their generation and their targets at molecular level. In this context, we aim to continue to contribute to the elucidation of the molecular mechanisms and the pathophysiological consequences of redox processes by addressing questions that are timely and relevant to the human health. Thus, the sources and fates of oxidants derived from bicarbonate buffer will be examined. We contributed to demonstrate that bicarbonate buffer modulates redox processes and are convinced that recognition of the oxidants derived from it will provide new perspectives to the understanding and control of numerous pathophysiological states and clinical conditions such as emphysema, respiratory muscle paralysis and pulmonary fibrosis. Also, we aim to advance in understanding structural and mechanistic aspects that the pro-oxidant activities of the enzyme superoxide dismutase1. It is expected that these studies will contribute to the elucidation of neurodegenerative processes, in particular those associated with amyotrophic lateral sclerosis. In addition, we will continue to study the thiol proteins as controllers and sensors of biological oxidants because these proteins only recently been recognized as players in redox processes and our previous kinetic and mechanistic studies provided insights about their multiple physiological roles. Finally, we will continue to study the mechanisms by which the nitroxides tempol is protective against oxidative and nitrosoactive conditions in vitro and in experimental animals. In our view these studies are relevant because nitroxides may constitute new antioxidant therapies, including to presently untreatable diseases such as multiple sclerosis and amyotrophic lateral sclerosis. (AU)

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)

QUEIROZ, RAPHAEL F.; PAVIANI, VERONICA; COELHO, FERNANDO R.; MARQUES, EMERSON E.; DI MASCIO, PAOLO; AUGUSTO, OHARA. The carbonylation and covalent dimerization of human superoxide dismutase 1 caused by its bicarbonate-dependent peroxidase activity is inhibited by the radical scavenger tempol. Biochemical Journal, v. 455, n. 1, p. 37-46, OCT 1 2013. (08/57721-3, 07/54541-1)

QUEIROZ, RAPHAEL F.; PAVIANI, VERONICA; COELHO, FERNANDO R.; MARQUES, EMERSON E.; DI MASCIO, PAOLO; AUGUSTO, OHARA. The carbonylation and covalent dimerization of human superoxide dismutase 1 caused by its bicarbonate-dependent peroxidase activity is inhibited by the radical scavenger tempol. Biochemical Journal, v. 455, p. 10-pg., 2013-10-01. (08/57721-3, 07/54541-1)