Superoxide dismutase MnSOD and

Enzymes which contain Mn include pyruvate carboxylase, argi-nase, and superoxide dismutase. This paper will focus on the role of Mn as a component of Mn superoxide dismutase (MnSOD) and the functional significance of alterations in the activity of this enzyme. 

These are (1) the copper-zinc superoxide dismutases, CuZnSOD, °° ° found in almost all eukaryotic cells and a very few prokaryotes, and (2) the manganese and iron superoxide dismutases, MnSOD and FeSOD, the former found in the mitochondria of eukaryotic cells, and both found in many prokaryotes. Recent studies of bacterial and yeast mutants that were engineered to contain no superoxide dismutases demonstrated that the cells were unusually sensitive... 

Two radicals that play predominant roles as initiators of lipid peroxidation are the hydroxyl radical (OH ) and the peroxynitrite radical (OONO ). The superoxide anion radical (02 ), which is generated during the electron transport process in mitochondria, is involved in the generation of both OH and OONO . Superoxide dismutase (MnSOD and Cu/ZnSOD) converts O2 to hydrogen peroxide (H2O2), which is then converted to... 

The mitochondrial dysfunctionality seen in manganese neurotoxicity might be related to the accumulation of reactive oxygen species (Verity, 1999). Mitochondrial Mn superoxide dismutase (MnSOD) is found to be low or absent in tumour cells and may act as a tumour suppressor. It is induced by inflammatory cytokines like TNF, presumably to protect host cells. In a rat model, iron-rich diets were found to decrease MnSOD activity, although a recent study reported that in rat epithelial cell cultures iron supplementation increased MnSOD protein levels and activity, but did not compromise the ability of inflammatory mediators like TNF to further increase the enzyme activity (Kuratko, 1999). 

Hohmeier, H.E., Thigpen, A., Tran, V. V., Davis, R. andNewgard, C.B. (1998) Stable expression of manganese superoxide dismutase (MnSOD) in insulinoma cells prevents IL-1 beta-induced cytotoxicity and reduces nitric oxide production. J. Clin. Invest., 101, 1811-1820. 

Manganese superoxide dismutase (MnSOD) is a redox-active manganese enzyme that employs a mononuclear manganese ion at its active site. Discovered in 1970 (52), this enzyme catalyzes the dismuta-tion of superoxide (H02), to dioxygen and hydrogen peroxide, as shown in Scheme 2. Superoxide is the radical, one-electron-reduced... 

Studies on some cell lines have shown that in tumor models such as mouse epidermal 1B6 cells and MCF-7, ROS were observed to stimulate cell growth in monolayers. In other cell lines, ROS can also be involved in the pathogenesis of cancer. By promoting cell proliferation in the transformed cancer cell lines MCF-7, HeLa, and Jurkat cells, reduced antioxidant levels were implicated in malignant transformation. Overexpression of manganese superoxide dismutase (MnSOD), a normal cellular antioxidant, enzyme was reported to revert transformation or tumor-promotion response in these and other transformed cell tines, such as human melanoma (UACC-903) cells, human breast cancer (MCF-7) cells, and mouse epidermal JB6 cells. ... 

How to determine protonation modes in reaction centers of enzymes is a very important issue in biochemistry [1-8], The protonation is obviously related to the catalytic activities of active side chains of amino residues the protonation and deprotonation to side chains of charged acids such as Glu, Asp, Arg, Lys, and His yield Brpnsted-Lowry acids and bases, catalyzing various chemical reactions. Also in metalloenzymes and these model systems, protonations are often critical parts of the reaction mechanisms. For instance, in (1) the water-oxidizing center (WOC) in photosystem II [9-14], (2) the Mn dimeric center in catalase [15-21], and (3) the Mn center in Mn superoxide dismutases (MnSODs)[22,23], the following reactions proceed, respectively ... 

Epperly MW, Travis EL, Sikora C et al. (1999) Manganese [correction of Magnesium] superoxide dismutase (MnSOD) plasmid/liposome pulmonary radioprotective gene therapy modulation of irradiation-induced mRNA for IL-I, TNF-alpha, and TGF-beta correlates with delay of organizing alveolitis/fibrosis. Biol Blood Marrow Transplant 5 204-214... 

Superoxide dismutases (SODs) are a family of cytosolic metalloenzymes that specifically remove (reviewed by Omar etal., 1992). SOD distribution within the body is ubiquitous, being found in erythrocytes as well as most organs and cell types. Three distinct mammalian SOD forms exist CuZnSOD, MnSOD and extracellular SOD (EC-SOD). Their amino-acid sequences differ as well as the transition metals at their active sites. Rheumatoid synovial fluid contains low levels of SOD activity and hence little protection from ROM generated by infiltrating PMNs (Blake etcU., 1981). Furthermore, leucocytes from patients with RA are deficient in MnSOD, which might promote the extracellular leakage of O2 (Pasquier et al., 1984). 

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