The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Enhanced Electron Flux and Reduced Calmodulin Dissociation May Explain “Calcium-independent” eNOS Activation by Phosphorylation
Open accessAbstract
Bovine endothelial nitric oxide synthase (eNOS) is phosphorylated directly by the protein kinase Akt at serine 1179. Mutation of this residue to the negatively charged aspartate (S1179D eNOS) increases nitric oxide (NO) production constitutively, in the absence of agonist challenge. Here, we examine the potential mechanism of how aspartate at 1179 increases eNOS activity using purified proteins. Examination of NO production and cytochrome c reduction resulted in no substantial changes in the K(m)/EC(50) for L-arginine, calmodulin, and calcium, whereas there was a 2-fold increase in the rate of NO production for S1179D and a 2-4-fold increase in reductase activity (based on cytochrome c reduction). The observed increase in activity for both assays of NOS function indicates that a faster rate of electron flux through the reductase domain is likely the rate-limiting step in NO formation from eNOS. In addition, S1179D eNOS did show an increased resistance to inactivation by EGTA compared with wild type eNOS. These results suggest that a negative charge imposed at serine 1179, either by phosphorylation or by replacement with aspartate, increases eNOS catalytic activity by increasing electron flux at the reductase domain and by reducing calmodulin dissociation from activated eNOS when calcium levels are low.
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“NOX1 expression is activated by several factors including angiotensin II, PDGF, and thrombin (382, 492, 630, 695, 999).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [630]
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“Altogether, the role of NOX1 in cardiovascular disease seems secondary to NOX2, but still significant, as shown in several models (345, 380, 630, 854).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [630]
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“NOX1 deletion limits the blood pressure increase elicited by angiotensin II, although it is unclear if basal blood pressure levels are reduced (345, 346, 630).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [630]
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Nitric oxide synthases: regulation and function
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Metadata
- Authors
- McCabe, T. J., Fulton, D., Roman, L. J., & Sessa, W. C.
- Affiliations
- Yale University (US)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Sessa, William C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 275
- Issue
- 9
- Pages
- 6123-6128
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2090688283
- Cited by
- 387
- References
- 32
- Citations by year
- 2025: 6 · 2024: 3 · 2023: 5 · 2022: 11 · 2021: 13 · 2020: 18 · 2019: 4 · 2018: 11 · 2017: 8 · 2016: 9 · 2015: 16 · 2014: 18 · 2013: 14 · 2012: 21
- FWCI
- 14.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (HL61371, HL64793)
- National Heart, Lung, and Blood Institute (HL-61371, HL-64793, R01HL064793, HL 57665, R01HL057665)
- National Institute of General Medical Sciences (R01GM052419)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- endothelial nitric oxide synthase, eNOS phosphorylation, Akt, nitric oxide production, electron flux, reductase domain, calcium-independent activation, cytochrome c reduction, L-arginine
- MeSH terms
- Animals, Calcium, Calmodulin, Cattle, Egtazic Acid, Electrons, Enzyme Activation, Kinetics, Mutation, NADH Dehydrogenase, NADP, Nitric Oxide, Phosphorylation, Proto-Oncogene Proteins, Protein Serine-Threonine Kinases, Nitric Oxide Synthase, Dimerization, Proto-Oncogene Proteins c-akt, Nitric Oxide Synthase Type III, Static Electricity
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