ROS levels can increase dramatically during different physiological and pathological situations. This may result in significant damage to cell structures and cumulates into a situation known as oxidative stress. In addition to the production of noxious effects, oxidants can modulate phosphorylation signaling pathways. Protein tyrosine phosphorylation processes control many cellular functions, especially those involved in inter- and intracellular communication and coordination of complex functions like cell membrane structure, motility and proliferation.

We have employed proteomic techniques to identify differentially regulated proteins in the red cell membrane. Most of the proteins can be differentially phosphorylated in different oxidative conditions but the functional implications of such modifications are generally poorly understood. In particular, oxidative stress results in massive phosphorylation of the predominant membrane-spanning protein, band 3 on tyrosine residues 8 and 21. We studied the effect of hemichromes on the development of membrane complexes containing phosphorylated band 3 and on the development of areas of structural destabilization which can be selectively removed through membrane vesiculation. Our results suggest that red cells possess an active mechanism, regulated by Syk kinase, capable to remodel the red cell membrane during the course of their life and that could explain the decrease of membrane surface and hemoglobin content that characterize the senescent erythrocytes. This new redox signaling pathway apparently finalized to the repair of the plasma membrane and to the expulsion of hemoglobin degradation products could therefore play a role in the regulation of the erythrocyte life span preventing their premature removal.