Human extracellular superoxide dismutase

The three-dimensional structure of human extracellular superoxide dismutase (EC-SOD) is unknown. Studies of structure-function relationships have been severely limited by its poor production in mammalian cell lines and failure to be expressed in prokaryotic and yeast systems. In contrast, extra- and intracellular Cu- and Zn-containing superoxide dismutases (CuZn-SOD) are expressed very well in E. coli and yeast. CuZn-SOD is homologous to a large interior fragment of EC-SOD, but lacks its extra N-terminal and C-terminal domains. Fusions of either the N-terminal domain of EC-SOD or both the N- and C-terminal domains of EC-SOD to CuZn-SOD resulted in a domain-swapped enzyme that expressed well and whose characteristics resemble EC-SOD (Stenlund and Tibell, 1999). 

H13. Hjalmarsson, K., Marklund, S. L., Engstrom, A., and Edlund, T., Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase. Proc. Natl. Acad. Sci. U.SA. 84, 6340-6344 (1987). 

Stromqvist M, Houdebine L, Andersson J, et al. Recombinant human extracellular superoxide dismutase produced in milk of transgenic rabbits. Transgenic Res., 1997 6(4) 271-278. 

Zelko, IN. Mueller, MR. Folz, RJ. (2008). Transcription factors spl and sp3 regulate expression of human extracellular superoxide dismutase in lung fibroblasts. Am J Respir Cell Mol Biol, Vol. 39, No. 2, pp.243-251, ISSN 1044-1549. 

M8. Marklund, S. L., Extracellular superoxide dismutase in human tissues and human cell lines. J. Clin. Invest. 74, 1398-1403 (1984). 

Turunen, P., Puhakka, H.L., Heikura, T, Romppanen, E., Inkala, M Leppanen, 0., and Yla-Herttuala, S. (2006) Extracellular superoxide dismutase with vaccinia virus anti-inflammatory protein 35K or tissue inhibitor of metaDoproteinase-l Combination gene therapy in the treatment of vein graft stenosis in rabbits. Human Gene Therapy, 17, 405—414. 

Stralin, P. Marklund, SL. (2000). Multiple cytokines regulate the expression of extracellular superoxide dismutase in human vascular smooth muscle cells. Atherosclerosis, Vol. 151, No. 2, pp. 433-441, ISSN 0021-9150. 

Stenlund, P., and Tibell, L. A. (1999). Chimeras of human extracellular and intracellular superoxide dismutases. Analysis of structure and function of the individual domains. 

As mentioned above many tumor promoters induce a cellular prooxidant state. Because poly(ADP) ribosylation of chromosomal proteins could play a role in active oxygen-induced modulation of gene expression by PMA we studied the effect of antioxidants. As shown in Fig. 2 for human fibroblasts 3229 the extracellular addition of moderate concentrations of CuZn-superoxide dismutase and catalase suppressed the PMA-induced accumulation of poly(ADPR) by 80-100%. Heated catalase was inactive. The low molecular weight antioxidant butylated-hydroxytoluene also suppressed the increase in poly(ADPR). These results suggest that active oxygen produced in a superoxide driven Fenton reaction represents an intermediate in the mechanism of action of PMA. The fact that the same antioxidants had no effect on poly(ADPR) synthesis induced by MNNG further emphasizes the fundamental difference between the two agents. 

Human alveolar type 11 cells obtained from surgical resections expressed the extracellular form of superoxide dismutase mRNA (Su et al. 1997). 

Amphibole (crocidol-ite and amosite), serpentine (chrysotile), wollastonite, riebeglass beads Human and rabbit mesothelial cells in vitro Oligonucleosomal DNA fragmentation, loss of membrane phospholipid asymmetry, and nuclear condensation Asbestos fibres, not control particles, induced apoptosis in mesothelial cells by all assays. Induction of apoptosis was dose-dependent for all types of asbestos, with crocidolite (5 ng/cm ) inducing 15.0 1.1 % apoptosis versus control particles <4 %. Apoptosis induced by asbestos, but not by actinomycin D, was inhibited by extracellular catalase, superoxide dismutase in the presence of catalase, hypoxia (8 % oxygen), deferoxamine, 3-aminobenzamide [an inhibitor of poly(ADP-ribosyl) polymerase], and cytochalasin B. Only catalase and cytocha-lasin B decreased fibre uptake. Broaddus et al. (1996) Escape from asbestos-induced apoptosis could allow the abnormal survival of mesothelial cells with asbestos-induced mutations... 

Antonyuk, S.V., Strange, R.W., Marklund, S.L., Hasnain, S.S., 2009. The structure of human extracellular copper-zinc superoxide dismutase at 1.7 A resolution insights into heparin and collagen binding. J. Mol. Biol. 388, 310-326. 

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