Influence of the bicarbonte/carbon dixide buffer on biological oxidations: in vitro and cell culture studies

• Grant number: 21/01901-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2021
• End date: August 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Ohara Augusto
• Grantee: Matheus Paulino Romano
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

Although crucial for physiological pH control, as the pair bicarbonate/carbon dioxide (bicarbonate buffer), carbon dioxide is toxic to mammals in high levels (hypercapnia) as extensively reported. Usually considered a stable molecule, carbon dioxide reacts with biologically ubiquitous oxygen metabolites such as peroxynitrite and hydrogen peroxide, to produce the carbonate radical and peroxymonocarbonate, respectively. These oxidants are considered to play roles in the oxidative distress associated with nitric oxide overproduction and, into a less extent, with hypercapnia. The possibility of CO2 metabolites influencing redox signaling (stress) opened in 2019 with the demonstration that bicarbonate buffer increases peroxidation of thiol proteins involved in cell signaling, such as protein tyrosine phosphatase B1 and peroxiredoxins. In this project, we aim contributing to elucidate the redox reactions of the bicarbonate buffer and their implications in cell signaling and cell damaging pathways. Specifically, we will attempt to develop methodologies to detect peroxymonocarbonate in PMA activated macrophages and relate its detection to impairment of phagocytosis by these cells. The investigation of other properties and other cell-types is likely. We will also perform kinetic studies to elucidate contradictions with regard to the formation of peroxymonocarbonate from H2O2 and the HCO3-/CO2 pair and to analyze the influence of carbonic anhydrase in the process. (AU)