The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Ascorbic Acid Enhances Endothelial Nitric-oxide Synthase Activity by Increasing Intracellular Tetrahydrobiopterin
Open accessAbstract
Ascorbic acid enhances NO bioactivity in patients with vascular disease through unclear mechanism(s). We investigated the role of intracellular ascorbic acid in endothelium-derived NO bioactivity. Incubation of porcine aortic endothelial cells (PAECs) with ascorbic acid produced time- and dose-dependent intracellular ascorbic acid accumulation that enhanced NO bioactivity by 70% measured as A23187-induced cGMP accumulation. This effect was due to enhanced NO production because ascorbate stimulated both PAEC nitrogen oxide (NO(2)(-) + NO(3)(-)) production and l-arginine to l-citrulline conversion by 59 and 72%, respectively, without altering the cGMP response to authentic NO. Ascorbic acid also stimulated the catalytic activity of eNOS derived from either PAEC membrane fractions or baculovirus-infected Sf9 cells. Ascorbic acid enhanced bovine eNOS V(max) by approximately 50% without altering the K(m) for l-arginine. The effect of ascorbate was tetrahydrobiopterin (BH(4))-dependent, because ascorbate was ineffective with BH(4) concentrations >10 microm or in PAECs treated with sepiapterin to increase intracellular BH(4). The effect of ascorbic acid was also specific because A23187-stimulated cGMP accumulation in PAECs was insensitive to intracellular glutathione manipulation and only ascorbic acid, not glutathione, increased the intracellular concentration of BH(4). These data suggest that ascorbic acid enhances NO bioactivity in a BH(4)-dependent manner by increasing intracellular BH(4) content.
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Cites
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Ascorbate is an outstanding antioxidant in human blood plasma
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Self-citationCoronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease.
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Cited by
Role of Oxidative Modifications in Atherosclerosis
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Self-citationHalliwell, B., & Whiteman, M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705776 · Cited by 2,238
Vitamin C as an Antioxidant: Evaluation of Its Role in Disease Prevention
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Interactions of Peroxynitrite, Tetrahydrobiopterin, Ascorbic Acid, and Thiols
Kuzkaya, N., Weissmann, N., Harrison, D. G., & Dikalov, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302227200 · Cited by 692
Altered mitochondrial dynamics contributes to endothelial dysfunction in diabetes mellitus
Shenouda, S. M., Widlansky, M. E., Chen, K., Xu, G., Holbrook, M., Tabit, C. E., Hamburg, N. M., Frame, A. A., Caiano, T. L., Kluge, M. A., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.014506 · Cited by 570
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Metadata
- Authors
- Huang, A., Vita, J. A., Venema, R. C., & Keaney, J. F.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-06
- Volume
- 275
- Issue
- 23
- Pages
- 17399-17406
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2117894872
- Cited by
- 366
- References
- 63
- FWCI
- 16.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Huang, A., Vita, J. A., Venema, R. C., & Keaney, J. F. (2000). Ascorbic Acid Enhances Endothelial Nitric-oxide Synthase Activity by Increasing Intracellular Tetrahydrobiopterin. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m002248200
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