Xanthine oxidase-induced neuronal death via the oxidation of NADH: prevention by micromolar EDTA.

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Al-Gonaiah M, Smith RA, Stone TW

Xanthine oxidase-induced neuronal death via the oxidation of NADH: prevention by micromolar EDTA.

Brain Res. 2009 Jul 14;1280:33-42. doi: 10.1016/j.brainres.2009.05.024. Epub 2009 May 18.

PubMed ID

19450565 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
NADH	Xanthine dehydrogenase/oxidase	Protein	Humans	Unknown	Substrate	Details