Inducible nitric oxide synthase in the central nervous system of patients with X-adrenoleukodystrophy

J Neuropathol Exp Neurol. 2000 Dec;59(12):1063-9. doi: 10.1093/jnen/59.12.1063.

Abstract

X-Adrenoleukodystrophy (X-ALD) is an inherited peroxisomal disorder of deficient catabolism of very long-chain (VLC) fatty acids with resulting neuroinflammatory demyelinating disease. Our recent documentation of nitric oxide (NO)-mediated increase in VLC fatty acid levels in glial cells and demonstration of greater increase of VLC fatty acids levels in the inflammatory region (plaque) of X-ALD brain as compared to the normal-looking region away from the plaque prompted us to investigate the possible involvement of NO in the pathophysiology of X-ALD. Herein we provide evidence of the expression of inducible nitric oxide synthase (iNOS) in the CNS of X-ALD patients. In situ hybridization demonstrated that iNOS mRNA was present in brain tissues from X-ALD patients but not in normal controls. Double-labeling immunofluorescence studies using cell-specific markers confirmed that iNOS-expressing cells in the CNS of X-ALD were astrocytes and microglia/macrophages. Finally, antibodies against nitrotyrosine strongly immunoreacted with tissues from the center of the plaque region of X-ALD brains suggesting the presence of the NO reaction product nitrotyrosine in the CNS of X-ALD. Taken together, these results demonstrate that iNOS is expressed in the brains of patients with X-ALD and may contribute to the pathogenesis of the disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenoleukodystrophy / enzymology*
  • Adrenoleukodystrophy / metabolism
  • Adrenoleukodystrophy / pathology
  • Brain / enzymology*
  • Brain / metabolism
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • RNA, Messenger / metabolism
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism

Substances

  • RNA, Messenger
  • 3-nitrotyrosine
  • Tyrosine
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II