Mn superoxide dismutase

TNF-a elicits a wide range of responses in cells and tissues. Apart from causing the lysis of certain tumours (by mechanisms probably related to the ability of the target to induce the synthesis of the mitochondrial manganese-dependent superoxide dismutase, Mn-SOD), it can also kill normal cells. These effects on normal cells are more apparent when biosynthesis is blocked - for example, by the addition of inhibitors of macromolecular bio-... 

A particular feature however of a large number of tumour cell types is low levels of manganese-superoxide dismutase (Mn-SOD) activity [138]. Tumours are also usually low in copper, zinc-superoxide dismutase (Cu, Zn-SOD) activity and often also low in catalase activity [138]. Glutathione peroxidase levels are however quite variable. 

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). 

In ALS, abundant evidence points to the effects of per-oxynitrite in affected tissues. Significant increases in levels of NT moieties are detected on CSF proteins from ALS patients (Aoyama et al., 2000 Shaw and Williams, 2000), including Mn superoxide dismutase (Mn-SOD) which is only slightly increased in patients with AD and PD (Chou et al., 1996 Aoyama et al., 2000). Moreover, NT immunoreactivity is associated with motor neurons of the spinal cord and axons (Calin-gasan et al., 2005), and co-localizes to axonal conglomerates and spheroid neurofilament accumulations of upper and lower motor neurons (Chou et al., 1996) and with Ap-40 depositions within abnormal neurons (Calingasan et al., 2005). 

The main part of mitochondrial Oy is vectorially released to the matrix, where it encounters specific intramitochondrial Mn-superoxide dismutase (Mn-SOD) [21-23] (reaction 4 ). Steady state concentrations of 0.2-0.3 nM were estimated for the mitochondrial matrix, with a content of 10-40 pM Mn-SOD reaction centers [24]. The Oy released into the intermembrane space [11] reacts with cytochrome c, located on the P side of the inner membrane, and with the Cu, Zn-SOD of the intermembrane space [25] ... 

Inagaki, S., Suzuki, K., Taniguchi, N., and Takagi, H. (1991). Localization of Mn-superoxide dismutase (Mn-SOD) in cholinergic and somatostatin-containing neurons in the rat neostriatum. Brain Res. 549, 174-177. 

Biochemically, manganese is considered an essential trace element, participating in a number of hiomolecules superoxide dismutase (Mn-SOD), catalase, Mn-ribonucleotide reductase, Mn-peroxidase, ligninase, the o>ygen-evolving centre (OEC) of photosystem ii (PS-ii), and Mn-thiosulfate oxidase. The enzymes mechanisms are very diverse and include oxo-atom transfer (four-electron oxidation of water to diojygen in PS-ii, extradiol dioxygenase), electron transfer (SOD, catalase), reduction of ribonucleotides to water and deoxyribonucleotides and oxidation of thiosulfate to sulfate. ... 

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). 

Little information is available in the scientific literature on the contribution of ROls in regulating the type II cell response to direct interactions with silica particles. Increases in manganese superoxide dismutase (Mn-SOD) protein can be localized to type II cells following in vivo silica exposure in rats (143). Type II cells respond to an oxidant stress, such as hyperoxia, by increasing antioxidant enzymes (144) and chemokines (145,146). Thus, it is reasonable to hypothesize that the type II cell response to silica involves an oxidant-mediated component. 

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