Eat your spinach? The role of buffering reactions in clearing hydrogen

Mathematical Biology Seminar
Wednesday, November 5, 2008 - 11:00am for 1 hour (actually 50 minutes)
Skiles 255
Melissa Kemp – Dept of Biomedical Engineering, Georgia Tech
Christine Heitsch
Hydrogen peroxide has been long considered a harmful reactive oxygen species, but is increasingly appreciated as a cellular signaling molecule. The mechanism by which the cell buffers against intracellular H2O2 accumulation during periods of oxidative stress is not fully understood. I will introduce a detailed network model of the known redox reactions and cellular thiol modifications involved in H2O2 buffering. The model includes anti-oxidative contributions of catalase, glutathione peroxidase, peroxiredoxin, and glutaredoxin, in addition to the cytoplasmic redox buffers, thioredoxin and glutathione. Based on ordinary differential equations, the model utilizes mass action kinetics to describe changes in concentration and redox state of cytoplasmic proteins upon exposure to physiologically relevant concentrations of extracellular H2O2. Simulations match experimental observations of a rapid and transient oxidation of thioredoxin upon exposure to extracellular peroxide. The increase in the concentration of oxidized proteins predicted by the model is simultaneously accompanied by an increase in protein S-glutathionylation, possibly regulating signal transduction in cells undergoing oxidative stress. Ultimately, this network analysis will provide insight into how to target antioxidant therapies for enhanced buffering without impacting the necessary protein oxidation used by cells for signaling purposes.