Basal and stimulated protein S-nitrosylation in multiple cell types and tissues

Andrew J. Gow, Qiping Chen, Douglas T. Hess, Brian J. Day, Harry Ischiropoulos, Jonathan S. Stamler

Research output: Contribution to journalArticlepeer-review

271 Scopus citations


There is substantial evidence that protein S-nitrosylation provides a significant route through which nitric oxide (NO)-derived bioactivity is conveyed. However, most examples of S-nitrosylation have been characterized on the basis of analysis in vitro, and relatively little progress has been made in assessing the participant forms of nitric-oxide synthase (NOS) or the dynamics of protein S-nitrosylation in situ. Here we utilize antibodies specific for the nitrosothiol (SNO) moiety to provide an immunohistochemical demonstration that protein S-nitrosylation is coupled to the activity of each of the major forms of NOS. In cultured endothelial cells, SNO-protein immunoreactivity increases in response to Ca2+-stimulated endothelial NOS (eNOS) activity, and in aortic rings, endothelium-derived and eNOS-mediated relaxation (EDRF) is coupled to increased protein S-nitrosylation in both endothelial and associated smooth muscle cells. In cultured macrophages, SNO-protein levels increase upon cytokine induction of induced NOS (iNOS), and in PC12 cells, increased protein S-nitrosylation is linked to nerve growth factor induction of neuronal NOS (nNOS). In addition, we describe developmental and pathophysiological increases in SNO-protein immunoreactivity within human lung. These results, which demonstrate Ca2+, neurohumoral, growth factor, cytokine, and developmental regulation of protein S-nitrosylation that is coupled to NOS expression and activity, provide unique evidence for the proposition that this ubiquitous NO-derived post-translational protein modification serves as a major effector of NO-related bioactivity.

Original languageEnglish (US)
Pages (from-to)9637-9640
Number of pages4
JournalJournal of Biological Chemistry
Issue number12
StatePublished - Mar 22 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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