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On the mechanism by which vascular endothelial cells regulate their oxygen consumption
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Two enzymes, soluble guanylyl cyclase and cytochrome c oxidase, have been shown to be exquisitely sensitive to nitric oxide (NO) at low physiological concentrations. Activation of the soluble guanylyl cyclase by endogenous NO and the consequent increase in the second messenger cyclic GMP are now known to control a variety of biological functions. Cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, is inhibited by NO. However, it is not clear whether NO produced by the constitutive NO synthase interacts with cytochrome c oxidase, nor is it known what the biological consequences of such an interaction might be. We now show that NO generated by vascular endothelial cells under basal and stimulated conditions modulates the respiration of these cells in response to acute changes in oxygen concentration. This action occurs at the cytochrome c oxidase and depends on influx of calcium. Thus, NO plays a physiological role in adjusting the capacity of this enzyme to use oxygen, allowing endothelial cells to adapt to acute changes in their environment.
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“Rotenone or amobarbital (a reversible inhibitor of complex I) given just before the onset of cardiac ischemia resulted in improved oxidative phosphorylation and retention of cytochrome c in mitochondria isolated during ischemia or on reperfusion (82, 85).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [85]
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Metadata
- Authors
- Clementi, E., Brown, G. C., Foxwell, N., & Moncada, S.
- Affiliations
- University College London (GB)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-02-16
- Volume
- 96
- Issue
- 4
- Pages
- 1559-1562
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC15516
- OpenAlex
- W2067637944
- Cited by
- 296
- References
- 38
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 8 · 2015: 9 · 2014: 8 · 2013: 11 · 2012: 7
- FWCI
- 14.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Consiglio Nazionale delle Ricerche
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- nitric oxide, vascular endothelial cells, oxygen consumption, cytochrome c oxidase, soluble guanylate cyclase, cyclic GMP, nitric oxide synthase, mitochondrial respiration, calcium influx, oxygen sensing
- MeSH terms
- Animals, Aorta, Thoracic, Bradykinin, Calcium, Cells, Cultured, Egtazic Acid, Endothelium, Vascular, Nitric Oxide, Oxygen Consumption, Swine, omega-N-Methylarginine, NG-Nitroarginine Methyl Ester
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