CuZn-superoxide dismutase

Klapper 1, R Hagstrom, RFine, K Sharp and B Honig 1986. Focusing of Electric Fields in tire Actir e Sit of CuZn Superoxide Dismutase Effects of Ionic Strength and Amino-Acid Substitution. Proteins Structure, Function and Genetics 1 47-59. 

Hirata, H., Ladenheim, B., Carlson, E., Epstein, C., Cadet, J.L. Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain attenuation in CuZn-superoxide dismutase transgenic mice. Brain Res. 714 95, 1996. 

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. 

Andersen,P.M.,Nilsson,P.,Ala-Hurula,V. et al.Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat. Genet. 10 61-66,1995. 

These systems are also described as normal copper proteins due to their conventional ESR features. In the oxidized state, their color is light blue (almost undetectable) due to weak d-d transitions of the single Cu ion. The coordination sphere around Cu, which has either square planar or distorted tetrahedral geometry, contains four ligands with N and/or 0 donor atoms [ 12, 22]. Representative examples of proteins with this active site structure (see Fig. 1) and their respective catalytic function include galactose oxidase (1) (oxidation of primary alcohols) [23,24], phenylalanine hydroxylase (hydroxy-lation of aromatic substrates) [25,26], dopamine- 6-hydroxylase (C-Hbond activation of benzylic substrates) [27] and CuZn superoxide dismutase (disproportionation of 02 superoxide anion) [28,29]. 

Ogawa et al. (1997) investigated the formation of H202 and the superoxide radical (02 ) in spinach (Spinacia oleracea) hypocotyls with the use of histochemical stains. Nitroblue tetrazolium (NBT) is used to detect 02 radicals. The colored reaction product formazan was only detected in the vascular tissue of developing spinach hypocotyls if CuZn-superoxide dismutase (CuZn-SOD E.C. 1.15.1.1) was inhibited by DDC... 

Figure 2-9. Formation of H202 through the concerted action of NAD(P)H oxidase and CuZn-superoxide dismutase, as proposed by Ogawa et al. (1997).

Ogawa, K., Kanematsu, S., and Asada, K., 1997, Generation of superoxide anion and localization of CuZn-superoxide dismutase in the vascular tissue of spinach hypocotyls their association with lignification, Plant Cell Physiol. 38 1118-1126. 

Francis 1W, Hosier BA, Brown RHJ, Fishman PS (1995) CuZn superoxide dismutase (SOD-l) tetanus toxin fragment C hybrid protein for targeted delivery of SOD-1 to neuronal cells. J Biol Chem 270 15434 12... 

M7. Marklund, S, Nordensson, I, and Back, O., Normal CuZn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase in Werner s syndrome. J. Gerontol. 36 405 109 (1981). 

T4. Teixeira, HD, Schumacher, RI, and Meneghini, R., Lower intracellular hydrogen peroxide levels in cells overexpressing CuZn-superoxide dismutase. Proc. Natl. Acad. Sci. USA 95, 7872-7875 (1998). 

Chan PH, Schmidley JW, Fishman RA, Longar SM (1984) Brain injury, edema, and vascular permeability changes induced by oxygen-derived free radicals. Neurology 34 315-320 Chan PH, Yang GY, Chen SF, Carlson E, Epstein CJ (1991) Cold-induced brain edema and infarction are reduced in transgenic mice overexpressing CuZn-superoxide dismutase. Ann Neurol... 

Kimelberg HK (2004) Water homeostasis in the brain basic concepts. Neuroscience 129 851-860 Kinouchi H, Epstein CJ, Mizui T, Carlson E, Chen SF, Chan PH (1991) Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. Proc Natl Acad Sd USA 88 11158-11162... 

Orgotein, an enzyme (CuZn superoxide dismutase) that is present in all mammalian cells, is obtained from bovine liver by several steps, including chromatography. It can be given parenterally or topically. Reliable published clinical experience of its properties is limited. In Germany, marketing approval for orgotein was suspended because of severe reactions and deaths, mostly due to hypersensitivity (SEDA-18,107). 

B6. Barra, D., Martini, F., Bannister, J. V., Shinina, M. E., Rotilio, G., Bannister, W. H., and Bossa, F., The complete amino acid sequence of human CuZn superoxide dismutase. FEBS Lett. 120, 53-56 (1980). 

Sinet, P.-M., and Gather, P., Inactivation of the human CuZn superoxide dismutase during exposure to 02 and H202. Arch. Biochem. Biophys. 212,411-416 (1981). 

Murakami K, Kondo T, Epstein CJ, Chan PH. Overexpression of CuZn-superoxide dismutase reduces hippocampal injury after global ischemia in transgenic mice. Stroke 1997 28 1797-1804. 

Kondo T, Reaume AG, Huang TT, et al. Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia. J Neurosci 1997 17 4180-4189. 

Dameron, C.T. and Harris, E.D. (1987a) Regulation of aortic CuZn-superoxide dismutase with copper. Biochem. J. 248 661-668. 

Intracellular transport of metal ions has been a very well studied research area in the last few years. The most often-cited case of this transport involves copper transport in yeast by the copper metallochaperones 24, 25). Cu(I) enters the cytoplasm of yeast via copper transport receptors, and Cu(I) is bound by one of three transport proteins Lys7, Atxl, or Cox 17. Lys7 delivers copper to CuZn superoxide dismutase, Atxl delivers copper to ccc2 that activates an Fe(II) uptake system, and Cox 17 delivers copper to the mitochondria for the ultimate uptake into cytochrome c oxidase. A similar copper transport system has been reported in humans (26), and there may be a system in bacteria as well (27). Metal ion transport systems are known for iron, nickel, and manganese 24, 25, 28). However, no cytoplasmic Zn(II) transporters have been identified in... 

Fig. 2. Effect of inhibitors of de novo RNA and protein synthesis and of the antioxidant enzymes CuZn-superoxide dismutase and catalase on PMA-induced accumulation of poly(ADPR) in human fibroblasts 3229 (for experimental conditions see text)...

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. 

When a bolus of 6xl0 IU/2 ml human recombinant CuZn-superoxide dismutase per kg rat was administered intravenously 72 h before transient occlusion of the middle cerebral artery, the infarct area and volume assessed with the 2,3,5-triphenyltetrazolium stain showed that the administration of human recombinant CuZn-superoxide dismutase suppressed the development of neuronal tolerance induced by preconditioning (Mori et al. 

Expression of 72-kDa heat-shock protein at 72 h after preconditioning was considerably reduced in rats treated with human recombinant CuZn-superoxide dismutase compared with those treated with vehicle. 

In CuZn-superoxide dismutase-transfected BV-2 murine microghal cells, the expression and activity increased after hpopolysaccharide stimulation (Chang et al. 2001). On the other hand, upon activation by EPS, these cells produced less NO, IL-ip, and TNF-a than the parental microghal cells. 

CuZn-superoxide dismutase in 26-month-old rats compared with. 8-month-old animals had decreased from 2.05 0.09x10 units perg cerebral tissue to 1.85 0.10xl0 units perg cerebral tissue (Gomi and Matsuo 1995). 

The presence of CuZn-superoxide dismutase, Mn-superoxide dismutase or Mn(II) enhanced the frequency of DNA damage induced by HjOj and Cu(II), and altered the site-spedfidty of the latter H2O2 induced Cu(ll)-dependent DNA damage with high frequency at the 5 -guanine of poly G sequences when superoxide dismutases were added, the frequency of cleavages at thymine and cytosine residues increased (Midorikawa and Kawanishi 2001). 

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