Peroxiredoxin II (Prdx II; a typical 2‐Cys Prdx) has been originally isolated from erythrocytes, and its structure and peroxidase activity have been adequately studied. Mice absent to Prdx II proteins had heinz bodies in their peripheral blood, and morphologically abnormal cells were detected in the dense red blood cell (RBC) fractions, which contained markedly higher levels of reactive oxygen species (ROS). In this study, a labeling experiment with the thiol‐modifying reagent biotinylated iodoacetamide (BIAM) in Prdx I‒/‒ mice revealed that a variety of RBC proteins were highly oxidized. To identify oxidation‐sensitive proteins in Prdx II‒/‒ mice, we performed RBC comparative proteome analysis in membrane and cytosolic fractions by nano‐UPLC‐MSE shotgun proteomics. We found oxidation‐sensitive 54 proteins from 61 peptides containing cysteine oxidation, and analyzed comparative expression pattern in healthy RBCs of Prdx II+/+ mice, healthy RBCs of Prdx II‒/‒ mice, and abnormal RBCs of Prdx II‒/‒ mice. These proteins belonged to cellular functions related with RBC lifespan maintain, such as cytoskeleton, stress‐induced proteins, metabolic enzymes, signal transduction, and transporters. Furthermore, protein networks among identified oxidation sensitive proteins were analyzed to associate with various diseases. Consequently, we expected that RBC proteome may provide clues to understand redox‐imbalanced diseases.

• Tae‐Hoon Lee(Department of Oral Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University)
• Hee‐Young Yang(Department of Oral Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University)
• Hoon‐In Choi(Department of Oral Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University)
• Gia‐Buu Tran(Department of Oral Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University)
• Ung Yang(Department of Oral Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University)