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)

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 > School of Psychology & Neuroscience; College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Brain Research
• ISSN: 0006-8993
• Published Online: 18 May 2009