title: Acute hypoxia-induced depletion of striatal nitric oxide synthase pathway.
abstract: Hypoxia-induced alteration of nitric oxide (NO) production may lead to brain disease, especially in the areas most sensitive to oxygen deficiency, such as the striatum. To date, the behaviour of the striatal NO pathway under hypoxia/reoxygenation remains unknown and its elucidation constitutes the aim of this work. Wistar rats were submitted to hypoxia (20min) and analyzed after 0h, 24h, and 5 days of reoxygenation. Expression, activity, and location of the NO synthase (NOS) isoforms (neuronal, endothelial, and inducible) as well as nitrated protein expression were analyzed in the rat striatum. NO levels were indirectly quantified as nitrates and nitrites (NO(x)), which act as NO-generating molecules. NOS isoform mRNA levels remained unaltered in hypoxic groups vs. normoxic control. However, quantification of immunoreaction showed a significant decrease in eNOS and nNOS after hypoxia. While in situ NOS activity and NO(x) levels fell, levels of nitrotyrosine-modified proteins rose throughout the reoxygenation period. Our data revealed the great complexity of the NO pathway, showing that both acute hypoxia and the successive recovery period down-regulated the NOS system in the rat striatum. However, under hypoxia/reoxygenation NO may be produced in a NOS-independent way from the NO-storage molecules, compensating for the hypoxia-reduced NOS activity.
authors.affiliation: Department of Health Science, University of Jaén, Paraje Las Lagunillas s/n, 23071 Jaén, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Molina
authors.forename: Alma
authors.initials: A
authors.lastname: Rus
authors.forename: Juan Ángel
authors.initials: JÁ
authors.lastname: Pedrosa
authors.forename: María Luisa
authors.initials: ML
authors.lastname: del Moral
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase