Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of acute ammonia intoxication on reactive oxygen species production by different sources in rat brain were studied. Ammonia intoxication in vivo leads to reduced activity of superoxide dismutase (SOD), catalase and glutathione peroxidase in brain nonsynaptic mitochondria and increased formation of O(2)(-) by submitochondrial particles. It also results in increased xanthine oxidase (XO) activity and decreased xanthine dehydrogenase (XDH)/XO activity ratio indicating conversion of XDH to XO and also increases monoamine oxidase A (MAO-A) activity but not of MAO-B. Blocking NMDA receptors with MK-801 prevents ammonia-induced oxidative stress, XDH to XO conversion and MAO-A activation. Ammonia intoxication did not lead to H(2)O(2) formation by mitochondria, in spite of increased O(2)(-) generation. The main source of H(2)O(2) in the mitochondrial matrix was Mn-SOD. Ammonia intoxication in vivo leads to increased superoxide and decreased hydrogen peroxide in nonsynaptic brain mitochondria. Increased superoxide is due to increased formation by the respiratory chain and by xanthine and aldehyde oxidases and decreased elimination by antioxidant enzymes. The reduced formation of hydrogen peroxide is due to the reduced activity of Mn-SOD. Prevention of ammonia-induced production of reactive oxygen species by MK-801 supports the idea that it is mediated by activation of NMDA receptors.
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PMID:Sources of oxygen radicals in brain in acute ammonia intoxication in vivo. 1288 41

The oxidation of xanthine by xanthine oxidase (XO) or xanthine dehydrogenase represents an important source of reactive oxygen species (ROS), which contribute to the damaging consequences of cerebral ischemia, inflammation, and neurodegenerative disorders. However, both enzymes are also able to act on reduced nicotinamide adenine dinucleotide (NADH). The FAD binding site to which NADH binds is distinct from that of the xanthine binding site. We report that the combination of xanthine oxidase and NADH is toxic to cultures of cerebellar granule neurons. Protection by superoxide dismutase (Cu,Zn-SOD or Mn-SOD) or catalase indicates mediation of the toxicity by superoxide and hydrogen peroxide. In addition, pre-incubating XO with EDTA at concentrations as low as 2 microM, prevented the toxicity, indicating that a metal contaminating XO is involved in producing the toxic effects of XO/NADH. It is possible that such a metal might play a role in the toxicity of XO in vivo.
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PMID:Xanthine oxidase-induced neuronal death via the oxidation of NADH: prevention by micromolar EDTA. 1945 May 65