ABSTRACT
Oxidative stress due to production of reactive oxygen species occurs in a variety of pathological and physiological conditions including diabetes and inflammation (1). Under the normal aging process or diabetic conditions, nonenzymatic glycosylation, designated as the glycation reaction (the Maillard reaction), occurs and this reaction also produces reactive oxygen species (2). On the other hand, in inflammatory processes, reactive oxygen species such as NO are produced by stimulation by cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF)-a. The antioxidative enzymes such as Cu,Znsuperoxide dismutase (SOD), Mn-SOD, glutathione peroxidase (GPx), and catalase play a pivotal role in scavenging the reactive oxygen species. However, under hyperglycemic conditions or in inflammatory processes, the major scavenging enzymes, Cu,Zn-SOD and GPx, are inactivated by the reactive oxygen species generated in the cells. Moreover, gene expression of other antioxidative enzymes including Mn-SOD, catalase and glutathione S-transferases 1 and 2 are downregulated by transforming growth factor p i (3). These events may suggest that oxidative stress is enhanced by downregulation of antioxidative enzymes at transcriptional and posttranslational levels. In this review we focus on the role of antioxidative enzymes in inflammation and diabetes as well as in a typical neurodegenerative disease, familial amyotrophic lateral sclerosis.
