Molecular cloning of constitutive endothelial nitric oxide synthase: evidence for a family of related genes
Abstract
Nitric oxide (NO) is synthesized in vascular endothelial cells, and appears to play an important role in the control of blood pressure and platelet aggregation. A detailed understanding of the regulation of NO synthesis by endothelial cells has been hampered by the lack of molecular clones for endothelial NO synthase; we now report the isolation and characterization of such clones. The constitutive NO synthases present in endothelial cells and in brain share common biochemical and pharmacologic features. We purified NO synthase from bovine brain, and determined the amino acid sequence of several tryptic peptides. These sequence data were utilized to design PCR-generated NO synthase cDNA probes, which were used to isolate clones encoding NO synthase from a bovine aortic endothelial cell (BAEC) cDNA library. A full-length NO synthase cDNA clone was isolated, representing a protein of 1,205 amino acids with a molecular mass of 133 kDa. The deduced amino acid sequence of the BAEC NO synthase cDNA differs at numerous residues from the sequence determined for the purified bovine brain protein, and shows 50-60% sequence identity with recently isolated molecular clones for murine macrophage and rat brain NO synthase isoforms. Bovine genomic Southern blots probed with bovine brain and BAEC NO synthase cDNA probes identify distinct bands, indicating that these cDNAs are the products of different genes. Prolonged treatment of BAEC with the cytokine TNF alpha, which results in a marked increase in NO synthase activity, is associated with a decrease in the abundance of the 4.8-kb BAEC NO synthase transcript.(ABSTRACT TRUNCATED AT 250 WORDS)
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TNFα downregulates NOS3 expression and abundance by decreasing the stability of NOS3 mRNA, effectively shortening its half-life.
“was shown to downregulate NOS3 expression and abundance [123, 131-134] by decreasing the stability of NOS3 mRNA [135, 136], effectively shortening its half-life [137].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [131]
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- Authors
- Michel, T., & Lamas, S.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Michel, Thomas
- Venue
- Journal of Cardiovascular Pharmacology
- Published
- 1992-04
- Volume
- 20
- Pages
- S45-S49
- ISSN
- 0160-2446 (ISSN-L)
- OpenAlex
- W2332106286
- Cited by
- 24
- References
- 0
- Citations by year
- 2024: 1 · 2018: 1 · 2016: 1 · 2014: 5
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cardiovascular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- endothelial nitric oxide synthase, nitric oxide, cDNA cloning, gene family, amino acid sequence, tryptic peptides, bovine aortic endothelial cells, bovine brain, TNF-α, gene expression regulation, blood pressure regulation, platelet aggregation
- MeSH terms
- Amino Acid Oxidoreductases, Amino Acid Sequence, Animals, Aorta, Brain, Cattle, Cloning, Molecular, Endothelium, Vascular, Multigene Family, Macrophages, Molecular Sequence Data, Tumor Necrosis Factor-alpha, Blotting, Southern, Gene Library, Sequence Alignment, Sequence Analysis, Nitric Oxide Synthase
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