Superoxide dismutases extracellular

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). 

Karlsson, K., Sandstrom, J., Edlund, A., Edlund, T. and Mark-lund, S.L. (1993). Pharmacokinetics of extracellular superoxide dismutase in the vascular system. Free Rad. Biol. Med. 14, 185-190. 

Ou, X., Tang, L., McCrossan, M., Henkle-Diihrsen, K. and Selkirk, M.E. (1995) Brugia malayi localisation and differential expression of extracellular and cytoplasmic CuZn superoxide dismutases in adults and microfilariae. Experimental Parasitology 80, 515-529. 

Sheng, H., Bart, R. D., Oury, T. D., Pearlstein, R. D., Crapo, J. D. and Warner, D. S. Mice overexpressing extracellular superoxide dismutase have increased resistance to focal cerebral ischemia. Neuroscience 88 185-191,1999. 

The enzyme superoxide dismutase (SOD) occurs in three forms in mammalian systems (1) CuZnSOD (SOD1) found in the cytosol, (2) MnSOD (SOD2) found in mitochondria, and (3) CuZnSOD found in extracellular space (SOD3). Additionally, many bacterial SOD enzymes contain iron. SOD 1 has been discussed in detail... 

Park JW, Qi WN, Liu JQ, Urbaniak JR, Folz RJ, Chen LE (2005) Inhibition of iNOS attenuates skeletal muscle reperfusion injury in extracellular superoxide dismutase knockout mice. Microsurgery 25(8) 606-613... 

Trapping of peroxynitrite from rat alveolar macrophages by superoxide dismutase. Although the fotmation of peroxynitrite is drawn as superoxide reacting with nitric oxide in the extracellular space, the actual reactions may be a combination of the pathways shown in Fig. 40. 

Li Q, Bolli R, Qiu Y Tang X-L, Guo Y French BA. Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction. Circulation 2001 103 1893-1898. 

Chen ER Bittner HB, Davis RD, Van Trigt R Folz R. Physiological effects of extracellular superoxide dismutase transgene overexpression on myocardial function after ischemia and reperfusion injury. J Thorac Cardiovasc Surg 1998 I 15 450-458. 

Figure 5.5 Tryptic digest of extracellular superoxide dismutase separated by (a) reversed-phase HPLC, using 0.1% (v/v) trifluoracetic acid in an acetonitrile/water gradient, and (b) CZE, using a 100 mM phosphate buffer, pH 2.5. (Reprinted from Ref. 15 with permission.)...

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). 

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

Several lipophilic hydroxyl-radical scavengers inhibited formation of PBN adducts [104-110], By virtue of its amphiphilic nature, PBN could trap radicals formed in both intra- and extracellular compartments. Consistent with this, several studies have reported only partial inhibition of PBN adducts in the presence of catalase, superoxide dismutase and water-soluble iron chelators [95]. 

The Oj" is transformed to H2O2 by the superoxide dismutase (SOD), the enzyme present in the cytoplasm of most mammalian cells and in the extracellular fluids. 

Oury, T. D., Piantadosi, C. A., andCrapo, J. D., Cold-induced brain edema in mice. Involvement of extracellular superoxide dismutase and nitric oxide. J. Biol. Chem. 268,15394—15398 (1993). 

A number of copper requiring enzymes are located at the cell surface or are exported into the extracellular milieu. Examples of such secretory Cu-enzymes include copper requiring ferroxidases that fimction in iron transport (e g. ceruloplasmin, CP), enzymes for neurotransmission (peptidyl amidating enzyme and dopamine hydroxylase), an extracellular superoxide dismutase (SOD) that fimctions in antioxidant defense and enzymes for formation of connective tissue (lysyl oxidase), and pigments (tyrosinase) (reviewed in ). En route to their designated location, each of these enzymes passes through a specialized compartment of the late Golgi where copper insertion takes place. 

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