Manganese SOD and

Because glutamate acting via NMDA receptors stimulates NO formation, it would be logical to expect that NOS neurons would be the first cells to succumb to excess NMDA receptor stimulation. However, NOS neurons are resistant to NMDA and NO neurotoxicity (Dawson and Snyder, 1994). It is unknown why NOS neurons are resistant to NMDA and NO neurotoxicity, but they probably possess protective factors that render them relatively resistant to the toxic NO environment they create. NOS neurons within the striatum are enriched in manganese SOD, and SOD in these neurons may... 

Li et al. (2002) THP-1 DEP 10, 25, 50, 100, 200 pg/ml, 16, 18 h Western blotting for HMOX-1, manganese-SOD, and c-Jun N-terminal kinase cascade (INK), apoptosis, GSH/GSSG ratio HMOX-1 expression at low oxidative stress, proceeds to INK activation and IL-8 secretion at intermediary level, and cellular toxicity observed at higher level... 

SOD comprises a family of metalloproteins primarily classified into four groups copper, zinc-containing SOD (Cu, Zn-SOD), manganese-containing SOD (Mn-SOD), iron-containing SOD (Fe-SOD) and nickel-containing SOD (Ni-SOD). In the following studies, we will only focus on the uses of the former three kinds of SODs to construct SOD-based 02 biosensors since the last one, Ni-SOD, is not commercially available. 

Manganese is the cofactor for catalases, peroxidases and superoxide dismutases, which are all involved in the detoxification of reactive oxygen species (SOD). We consider here the widely distributed Mn SOD, and then briefly describe the dinuclear Mn catalases. 

To prevent membrane damage, the red cell has an armoury of antioxidants, notably a manganese or selenium containing enzyme called superoxide dismutase (SOD) and the sulfydryl compound glutathione (GSH), a tripeptide of y-glutamate, cysteine and glycine. 

The metal-peroxo species are considered to have a side-on structure (bidentate coordination of the peroxide ligand) and to be very unstable in protic medium (8). Under physiological conditions, after the first protonation and formation of a hydroperoxo intermediate (Scheme 2), the second protonation of this intermediate can proceed in two distinctly different pathways. In one case the second protonation results in the release of hydrogen peroxide from the metal center, leaving the metal oxidation state unchanged (Scheme 2). This is a crucial step in the catalytic cycles of SODs and SORs, especially in the catalytic mechanism of manganese SODs, which exist in the hydrophobic mitochondrial matrix. If protonation is not efficient, the... 

Manganese is the third most abundant transition element [1]. It is present in a number of industrial, hiological, and environmental systems, representative examples of which include manganese oxide batteries [2] the oxygen-evolving center of photosystem II (PSII) [3] manganese catalase, peroxidase, superoxide dismutase (SOD), and other enzymes [4, 5] chiral epoxidation catalysts [6] and deep ocean nodules [7]. Oxidation-reduction chemistry plays a central role in the function of most, if not all, of these examples. 

The active site of manganese SOD contains a single five-coordinate Mn bound to three histidine imidazoles, a monoden-tate aspartate carboxylate, and a solvent molecule (H2O or OH , depending on the oxidation state) [103]. The catalytic cycle of the enzyme, which is illustrated in Fig. 16, incorporates the following oxidative and reductive steps ... 

In addition to the cytosolic SOD there is a longer 222-residue extracellular form that binds to the proteoglycans found on cell surfaces.522,527 Manganese SODs are found in mitochondria and in bacteria and iron SODs in plants and bacteria. They all appear to be important in protecting cells from superoxide radicals.522/532/533 This importance was dramatically emphasized when it was found that a defective SOD is present in persons (about 1 in 100,000) with a hereditary form of amylotrophic lateral sclerosis (ALS), which is also called Lou Gehrig s disease after the baseball hero who was stricken with this terrible disease of motor neurons in 1939 at the age of 36.534-536... 

Three types of SODs occur (1) extracellular (EC)-SOD, (2) manganese SOD found in the mitochondria, and (3) copper-zinc SOD found in the cytosol and nucleus. H202 can be converted to the highly toxic hydroxyl radical ("OH) via the iron-catalyzed Fenton reaction ... 

SODs have been used in animal models to limit damage by direct injection at sites of inflammation with effective, albeit transient, effects and the use of SODs as potential therapeutic agents has been the focus of intense debate [25], Recently, using a recombinant manganese SOD in two different experimental models of inflammation, we demonstrated an anti-inflammatory effect and showed correct dosing to be critical [26]. 

CD spectroscopy has also been used to study the metal-binding and reactivity properties of iron- and manganese-containing SODs. These enzymes metabolize the superoxide ion radical O2 into molecular oxygen and hydrogen peroxide. The Fe- and Mn-SOD enzymes are strictly metal specific. Jackson and Brunold show that, despite the fact that Fe replacement of Mn in the Mn-SOD enzyme [(Mn Fe)-SOD] results in an inactive enzyme, the CD spectrum of wild-type Fe-SOD and (Mn - Fe)-SOD are remarkably similar. This suggests that the destroyed enzyme activity, upon replacement of the metal, does not occm via distortion of the enzyme active site. 

Superoxide dismutase, more commonly called SOD, is an unusual enzyme that breaks down even the most destructive free radicals in the body. At least four different types of it are now known, involving five different trace elements as parts of the molecular structure. Those metals are iron, manganese, nickel, and, in one form of the enzyme, a combination of copper and zinc. Others may be discovered in the future. The SOD enzyme especially protects the nucleic acids of cells from attack by free radicals. This is very important because DNA damage is one way that cancer can develop in the body. 

---