Interaction of ROS and RNS with GSH and GSH/GPX Systems

Rapid reactivity amongst the free radicals and its capability to inflict severe damages to cell has evolved cell redox systems with multiple pathways of counteracting and counterbalancing mechanisms. One of the important cell redox pathways is glutathione (GSH) and GSH/glutathione peroxidase (GPX) enzyme system. In addition to eliminating hydrogen peroxide (H 2 O 2 ) and peroxynitrite (ONOO ‐ ), GSH and GPX act as a buffer to protect crucial proteins against pathological modifications. In recent year, GSH and GPX have been emphasized for providing a promising treatment avenue in vascular diseases including neurovascular and cardiovascular diseases. However, complexity of cellular redox system has limited the current understanding of GSH and GPX led mechanism which prevents cell damage in pathophysiological condition. In this study, we used systems approach to model GSH and the GSH/GPX system in the presence of nitric oxide (NO) and superoxide (O 2 •‐ ) derived species. Result shows that there is an indicated dividing line between oxidative stress and nitrosative stress as the ratio of [O 2 •‐ ]/[NO] less than or greater than one. Results provide quantitative information about GSH levels that leads to the depletion of N 2 O 3 and H 2 O 2 . In addition, reduced glutathione peroxidase (GPXr) assists GSH in removal of high levels of H 2 O 2 . The model predicted that the GPX antioxidant capabilities are dependent on the bioavailability of GSH. The levels of nitric oxide and superoxide derived species are dependent of the balance between these reactive and antioxidant species through interaction with GSH/GPX system. The results indicate that both GSH and GPX play an important role in removal of oxidative stress and GSH also plays an important role in detoxifying nitrosative stress.