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

Al-Gonaiah, M., Smith, R.A. and Stone, T.W. (2009) Xanthine oxidase-induced neuronal death via the oxidation of NADH: prevention by micromolar EDTA. Brain Research, 1280, pp. 33-42. (doi:10.1016/j.brainres.2009.05.024)

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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 [mu]M, 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

Item Type:Articles
Keywords:Xanthine oxidase, NADH, nicotinamide adenine dinucleotide, peroxide, cerebellar granule neurons, superoxide dismutase
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stone, Professor Trevor and Smith, Professor Robert
Authors: Al-Gonaiah, M., Smith, R.A., and Stone, T.W.
Subjects:Q Science > QR Microbiology
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Brain Research
ISSN:0006-8993
Published Online:18 May 2009

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