Manganese superoxide dismutase modeling

CL Eisher, J-L Chen, J Li, D Bashford, L Noodleman. Density-functional and electrostatic calculations for a model of a manganese superoxide dismutase active site in aqueous solution. J Phys Chem 100 13498-13505, 1996. 

Time-course of human manganese superoxide dismutase reaction after generation of superoxide by pulse radiolysisT The experiment demonstrates decrease in absorbance at 250 nm (e = 2000 M cm ) for a solution containing 0.5/aM enzyme, 50/aM EDTA, 10 mM sodium formate, and 2 mM sodium pyrophosphate at pH 9.4 and 20°C. The starting concentrations of superoxide were 11.6 /xhA (upper curve), 6.5 /aM (middle curve), and 3.4 /aM (lower curve). The calculated progress curves shown as solid lines were obtained by using the KINSIM software and the model of Bull et aF Reproduced here with the permission of the authors and the American Chemical Society. 

Fig. 4.13 The catalytic site in manganese superoxide dismutase (SOD2) [26] and a model compound...

The mechanisms by which manganese complexes and manganese superoxide dismutase react with superoxide radicals are of interest as knowledge of the kinetic parameters and the reaction pathways may allow the synthesis of model compounds with specific chemical features. These compounds may then have clinical application or may allow the control of specific redox chemistry in catalytic processes. 

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. ... 

Carroll, I.M., Andrus, J.M., Bruno-Barcena, J.M., et al. (2007). Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis. Am J Physiol... 

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). 

Moreover, CoQi0, menadione, ascorbate, and superoxide dismutase-mimetic manganese-5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTBAP) have been shown to mediate their antioxidant effects on the ROS and the oxidative stress involved in neuronal death in mitochondrial diseases (S4, T6). There is increasing evidence to support the role of ROS in cell death (Rl), and antioxidants appear to have benefits in animal models of mitochondrial disease (Wl). For example, Melov et al. (M9) reported that mice lacking mitochondrial MnSOD exhibited a... 

Manganese compounds of biologic importance are examined by pulse radiolysis e.g., the rate of dismutation of radiation-generated Of is catalyzed by Escherichia coli, Mn-containing superoxide dismutase involving electron transfer in which enzymes with Mn(IV), Mn(IIl), Mn(II) and Mn(I) oxidation states are involved. A kinetic model for the reaction mechanism of an Mn dismutase from Bacillus stearothermophilus accounts for the variation of the rate of decay on the concentrations of Oj, enzyme, HjOj, NaNj, KCN and H+. 

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