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Nitroso-redox status and vascular function in marginal and severe ascorbate deficiency

Record type: Article

Marginal vitamin C (ascorbic acid) deficiency is a prevalent yet underappreciated risk factor for cardiovascular disease. Along with glutathione, ascorbate plays important roles in antioxidant defense and redox signaling. Production of nitric oxide (NO) and reactive oxygen species and their interaction, giving rise to nitroso and nitrosyl product formation, are key components of the redox regulation/signaling network. Numerous in vitro studies have demonstrated that these systems are interconnected via multiple chemical transformation reactions, but little is known about their dynamics and significance in vivo. Aims: We sought to investigate the time-course of changes in NO/redox status and vascular function during ascorbate depletion in rats unable to synthesize vitamin C. Results: We here show that both redox and protein nitros(yl)ation status in blood and vital organs vary dynamically during development of ascorbate deficiency. Prolonged marginal ascorbate deficiency is associated with cell/tissue-specific perturbations in ascorbate and glutathione redox and NO status. Scurvy develops earlier in marginally deficient compared to adequately supplemented animals, with blunted compensatory NO production and a dissociation of biochemistry from clinical symptomology in the former. Paradoxically, aortic endothelial reactivity is enhanced rather than impaired, irrespective of ascorbate status. Innovation/Conclusion: Enhanced NO production and protein nitros(yl)ation are integral responses to the redox stress of acute ascorbate deprivation. The elevated cardiovascular risk in marginal ascorbate deficiency is likely to be associated with perturbations of NO/redox-sensitive signaling nodes unrelated to the regulation of vascular tone. This new model may have merit for the future study of redox-sensitive events in marginal ascorbate deficiency. Antioxid. Redox Signal. 00, 000-000.

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Citation

Garcia-Saura, Maria-Francisca, Saijo, Fumito, Bryan, Nathan S., Bauer, Selena, Rodriguez, Juan and Feelisch, Martin (2012) Nitroso-redox status and vascular function in marginal and severe ascorbate deficiency Antioxidants & Redox Signaling, 17, (7), pp. 937-950. (doi:10.1089/ars.2011.4201). (PMID:22304648).

More information

e-pub ahead of print date: 8 March 2012
Published date: 1 October 2012
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337516
URI: http://eprints.soton.ac.uk/id/eprint/337516
ISSN: 1523-0864
PURE UUID: b99ee715-7de7-45e9-ab97-152a65542853
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 26 Apr 2012 13:17
Last modified: 18 Jul 2017 06:02

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Contributors

Author: Maria-Francisca Garcia-Saura
Author: Fumito Saijo
Author: Nathan S. Bryan
Author: Selena Bauer
Author: Juan Rodriguez
Author: Martin Feelisch ORCID iD

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