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Acute hypoxia-induced depletion of striatal nitric oxide synthase pathway
► The functioning of NO system revealed great complexity in the hypoxic rat striatum. ► Acute hypoxia/reoxygenation down-regulated the NOS pathway in the rat striatum. ► NO may be produced in a NOS-independent way in the hypoxic rat striatum. Hypoxia-induced alteration of nitric oxide (NO) productio...
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Published in: | Journal of chemical neuroanatomy 2013-01, Vol.47, p.42-49 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | ► The functioning of NO system revealed great complexity in the hypoxic rat striatum. ► Acute hypoxia/reoxygenation down-regulated the NOS pathway in the rat striatum. ► NO may be produced in a NOS-independent way in the hypoxic rat striatum.
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 5days 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 (NOx), 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 NOx 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. |
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ISSN: | 0891-0618 1873-6300 |
DOI: | 10.1016/j.jchemneu.2012.12.003 |