Reevaluation of assay methods and establishment of kit for superoxide dismutase activity.

The current status of superoxide dismutase (SOD) is that it is an enzyme with diverse ramifications. This review attempts an understanding of SOD as a structural, functional, and biological entity. Accordingly, the review is in three parts. The first part discusses SOD in terms of protein structure, proceeding from primary to secondary and three-dimensional structure for the three forms of SOD: copper/zinc SOD, manganese SOD, and iron SOD. This is the order of structural knowledge of the enzyme. Iron SOD is an enzyme of prokaryotes and some higher plants. Manganese SOD is an enzyme of prokaryotes and eukaryotes. Copper/zinc SOD is an enzyme of eukaryotes and certain prokaryotes. The evolutionary relationships of the three forms of SOD, the status of the copper/zinc SOD gene in prokaryotes, and the cloning and sequencing of SOD genes are discussed. The second part of the review deals with the catalytic mechanism of SOD in the three forms of the enzyme. Structural and mechanistic conclusions from various spectroscopic studies are critically considered. A detailed picture is given of the active site of copper/zinc SOD. The third part is a review of SOD in the general context of oxygen toxicity. After consideration of the question of superoxide toxicity and superoxide pathology, several areas in which SOD has been investigated or used as a tool in a biochemical, pharmacological, or clinical context are discussed, including population genetics; trisomy 21; development and senescence; the nutritional copper, zinc, and manganese status; hemolysis and anemia; oxygen toxicity in the lung and nervous system; inflammation, autoimmune disease and chromosome breakage, ischemia and degenerative changes; radiation damage; and malignancy. A comprehensive picture is given of measurements of SOD activity in disease states, and the question of superoxide-related disease is considered at several points.

Aspects of the structure, function, and applications of superoxide dismutase

The importance of transition metals in biological processes has been well established. Copper (Cu) is a transition metal that can exist in oxidised and reduced states. This allows it to participate in redox and catalytic chemistry, making it a suitable cofactor for a diverse range of enzymes and molecules. Cu deficiency or toxicity is implicated in a variety of pathological conditions; therefore inorganic complexes of Cu have been investigated for their therapeutic and diagnostic potential. These Cu complexes have been shown to be effective in cancer treatment due to their cytotoxic action on tumour cells. Alternatively, Cu complexes can also modulate Cu homeostasis in the brain, resulting in protective effects in several models of neurodegeneration. In other diseases such as coronary heart disease and skin disease, the success of Cu complexes as potential therapeutics will most likely be due to their ability to increase SOD activity, leading to relief of oxidative stress. This review seeks to provide a broad insight into some of the diverse actions of Cu complexes and demonstrate the strong future for these compounds as potential therapeutic agents.

Copper complexes as therapeutic agents

Correlation between blood antioxidant levels and lipid peroxidation in rheumatoid arthritis

Superoxide dependent iron release from ferritin in inflammatory diseases

Superoxide-dismutase deficiency in rheumatoid arthritis

Superoxide dismutase (SOD) and glutathione peroxidase (GPX) protect aerobic organisms against the toxic superoxide anion and hydrogen peroxide, which are generated during phagocytosis by polymorphonuclear leucocytes (PMNs). PMNs of children with bacterial infections and with infectious hepatitis contained significantly elevated SOD activity, whereas GPX activity remained in the normal range. In contrast, PMNs of children with viral infections and rheumatoid arthritis exhibited a decreased SOD activity, while GPX activity was again unchanged. The children's age, sex or treatment did not effect the enzyme activities in PMNs. Since SOD generates bactericidal hydrogen peroxide and regulates the release of the toxic superoxide radical into the surrounding tissues, this study may add new understanding to the pathophysiological aspects of acute and chronic inflammatory processes.

Superoxide dismutase and glutathione peroxidase in polymorphonuclear leucocytes.

Various polymorphonuclear leukocyte (PMN) functions are dependent on an intact intracellular cytoskeleton consisting of the microtubules and the microfilaments To investigate the microtubule system in PMNs we observed the spontaneous, Colchicine and Diamide induced cap-formation by fluorescence microscopy in PMNs obtained from children with bacterial and viral infections, bronchial asthma, as well as during immunosuppressive therapy Children with bacterial infections demonstrated with 47±1% a significantly increased number of spontaneous capped PMNs compared to 22±1% capped cells obtained from controls Furthermore, 52±2% PMNs of children with bronchial asthma as well as 51±2% PMNs of patients on immunosuppressive therapy exhibited spontaneous surface capping There was no significant elevation in the number of capped PMNs (30±2%) obtained from children with viral infections Colchicine and Diamide increased the number of capped cells in control PMNs as well as in PMNs from patients to 69±1% and 67±1%, respectively Since the increased spontaneous cap formation in PMNs is associated with a defect of microtubule assembly, the various leukocyte function defects described in patients with bacterial infections, bronchial asthma or on immunosuppressive therapy may have to be considered the consequence of an altered microtubule system

M. Rister

Papers

Superoxide-dismutase deficiency in rheumatoid arthritis

Superoxide dismutase and glutathione peroxidase in polymorphonuclear leucocytes.

Concanavalin A capping in polymorphonuclear leukocytes