Role of reactive oxygen species in glomerulonephritis.

Small amounts of reactive oxygen species (ROS) are constantly produced in aerobic metabolism and have important roles in normal cell physiology e.g. signal transduction pathways. However, in pathophysiological conditions with increased levels of ROS, these molecules become relevant factors in the initiation and amplification of deleterious processes observed in inflammation, oncogenesis, and degenerative diseases [1,2]. ROS are products of the partial reduction of oxygen Fig. 1. Major reactive oxygen species. and can be generated by enzymatic and non-enzymatic reactions within cells and at the cell membrane [3,4]. Enzymes that generate ROS are termed oxidative on the availability of the free metal ions Fe2+ or Cu+, enzymes (Table 1) [5–16 ]. Major ROS are depicted in are the most reactive of the ROS [17]. Several defence Figure 1, which also shows the important reactions mechanisms exist to decrease the concentration of and catalysts involved. Hypochlorous acid produced ROS. Superoxide dismutases (SODs) catalyse the disby myeloperoxidase and hydroxyl radical (OHV ), mutation of superoxide anion to hydrogen peroxide which evolves from non-enzymatic reactions dependent 22 which is further degraded by glutathione peroxidases and catalase (Table 1) [18]. Besides these antioxidative enzymes, metal-binding proteins such as Table 1. Cellular localization of oxidative and antioxidative ferritin, transferrin, caeruloplasmin, and metallothionenzymes [5–16 ] ein are present to limit the generation of OHV [19]. The antioxidant defence is further complemented by Enyzme Localization the vitamins A, E, and C, and by bilirubin which act as scavengers of ROS [3,4]. Xanthine oxidoreductase Cytoplasm, peroxisomes Thus the balance between oxidative and antiNADPH–Oxidase Cell membrane, granula of leukocytes, nuclear membrane oxidative enzymes and other antioxidative components NADH–Oxidase Cell membrane, microsomes, determines the concentration of ROS and thereby, mitochondria physiological or pathophysiological ROS-related celluAldehyde oxidase Cytoplasm, mitochondria, microsomes lar effects. However, this simplified scheme is complicSulphite oxidase Cytoplasm, mitochondria, microsomes 450 Microsomes ated by the fact that oxidative and antioxidative Cu,Zn-SOD Cytoplasm, mitochondria, lysosomes enzymes are localized in specific extracellular and Mn-SOD Mitochondria intracellular compartments (Table 1). In addition, the Catalase Peroxisomes, cytoplasm expression of oxidative and antioxidative enzymes Glutathione peroxidases Mitochondria, cytoplasm, peroxisomes, varies between different organs and within different nuclear membrane cell types of an organ. Microlocal concentrations of ROS can therefore differ appreciably in a single cell or Cu,Zn-SOD, copper/zinc-superoxide dismutase; Mn-SOD, manganese superoxide dismutase. organ compartment (e.g. glomerulus, tubule, and interstitium of the kidney) [20]. Based on this compartCorrespondence and offprint requests to: Hermann-Josef Gröne MD, mentalization of ROS synthesis and degradation, it Department of Cellular and Molecular Pathology, German Cancer can be deduced that examination of ROS and the Research Centre (DKFZ) Heidelberg, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. enzymes involved in their metabolism in samples of