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Cited by 821

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes.

Open access
Geller, D A, Lowenstein, C J, Shapiro, R A, Nussler, A K, Di Silvio, M, Wang, S C, Nakayama, D K, Simmons, R L, Snyder, S H, Billiar, T R·1993·Proceedings of the National Academy of Sciences

Abstract

Nitric oxide is a short-lived biologic mediator for diverse cell types. Synthesis of an inducible nitric oxide synthase (NOS) in murine macrophages is stimulated by lipopolysaccharide (LPS) and interferon gamma. In human hepatocytes, NOS activity is induced by treatment with a combination of tumor necrosis factor, interleukin 1, interferon gamma, and LPS. We now report the molecular cloning and expression of an inducible human hepatocyte NOS (hep-NOS) cDNA. hep-NOS has 80% amino acid sequence homology to macrophage NOS (mac-NOS). Like other NOS isoforms, recognition sites for FMN, FAD, and NADPH are present, as well as a consensus calmodulin binding site. NOS activity in human 293 kidney cells transfected with hep-NOS cDNA is diminished by Ca2+ chelation and a calmodulin antagonist, reflecting a Ca2+ dependence not evident for mac-NOS. Northern blot analysis with hep-NOS cDNA reveals a 4.5-kb mRNA in both human hepatocytes and aortic smooth muscle cells following stimulation with LPS and cytokines. Human genomic Southern blots probed with human hep-NOS and human endothelial NOS cDNA clones display different genomic restriction enzyme fragments, suggesting distinct gene products for these NOS isoforms. hep-NOS appears to be an inducible form of NOS that is distinct from mac-NOS as well as brain and endothelial NOS isozymes.

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Metadata

Authors
Geller, D. A., Lowenstein, C. J., Shapiro, R. A., Nussler, A. K., Di Silvio, M., Wang, S. C., Nakayama, D. K., Simmons, R. L., Snyder, S. H., & Billiar, T. R.
Venue
Proceedings of the National Academy of Sciences
Published
1993-04-15
Volume
90
Issue
8
Pages
3491-3495
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2016687652
Cited by
821
References
7
FWCI
51.39
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. https://app.cochat.ai/papers/10.1073/pnas.90.8.3491
The paper
Geller, D. A., Lowenstein, C. J., Shapiro, R. A., Nussler, A. K., Di Silvio, M., Wang, S. C., Nakayama, D. K., Simmons, R. L., Snyder, S. H., & Billiar, T. R. (1993). Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.90.8.3491

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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