Previous studies have demonstrated that ubiquitin-proteasome system function is significantly decreased in the substantia nigra of Parkinson"s disease patients. In the present study, proteasome inhibitor Z-lle-Glu(OtBu)-Ala-Leucinal (PSI) was used to inhibit the function of the ubiquitin-proteasome system in PC12 cells to simulate Parkinson"s disease. Oxidatively modified proteins were identified to determine pathogenesis of Parkinson"s disease. Results demonstrated that 24 hours of 10 mu mol/L PSI-treatment in PC12 cells simulated pathological characteristics of Parkinson"s disease: neuronal degeneration and eosinophilic inclusion formation in neurons. In PSI-treated PC12 cells, three oxidative proteins and a molecular chaperone family member were detected: chaperonin containing t-complex polypeptide 1 subunit 3, glucose-regulated protein 58, and heat shock protein 70. This is the first study to demonstrate oxidative modification of a molecule family in a cell model of Parkinson"s disease induced with PSI.