title: Inducible nitric oxide synthase in the central nervous system of patients with X-adrenoleukodystrophy.
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.
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Gilg
authors.forename: A K
authors.initials: AK
authors.lastname: Singh
authors.forename: I
authors.initials: I
authors.lastname: Singh
mesh_terms: D000326:Adrenoleukodystrophy / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II