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A genetic analysis of nitrosative stress.

Publication ,  Journal Article
Foster, MW; Liu, L; Zeng, M; Hess, DT; Stamler, JS
Published in: Biochemistry
February 3, 2009

Nitrosative stress is induced by pathophysiological levels of nitric oxide (NO) and S-nitrosothiols (e.g., S-nitrosoglutathione, GSNO) and arises, at least in significant part, from the nitrosylation of critical protein Cys thiols (S-nitrosylation) and metallocofactors. However, the mechanisms by which NO and GSNO mediate nitrosative stress are not well understood. Using yeast Saccharomyces cerevisiae strains lacking NO- and/or GSNO-consuming enzymes (flavohemoglobin and GSNO reductase, respectively), we measured the individual and combined effects of NO and GSNO on both cell growth and the formation of protein-bound NO species. Our results suggest an intracellular equilibrium between NO and GSNO, dependent in part on cell-catalyzed release of NO from GSNO (i.e., "SNO-lyase" activity). However, whereas NO induces multiple types of protein-based modifications, levels of which correlate with inhibition of cell growth, GSNO mainly affects protein S-nitrosylation, and the relationship between S-nitrosylation and nitrosative stress is more complex. These data support the idea of multiple classes of protein-SNO, likely reflected in divergent routes of synthesis and degradation. Indeed, a significant fraction of protein S-nitrosylation by NO occurs in the absence of O(2), which is commonly assumed to drive this reaction but instead is apparently dependent in substantial part upon protein-bound transition metals. Additionally, our findings suggest that nitrosative stress is mediated principally via the S-nitrosylation of a subset of protein targets, which include protein SNOs that are stable to cellular glutathione (and thus are not metabolized by GSNO reductase). Collectively, these results provide new evidence for the mechanisms through which NO and GSNO mediate nitrosative stress as well as the cellular pathways of protein S-nitrosylation and denitrosylation involving metalloproteins, SNO lyase(s) and GSNO reductase.

Duke Scholars

Published In

Biochemistry

DOI

EISSN

1520-4995

Publication Date

February 3, 2009

Volume

48

Issue

4

Start / End Page

792 / 799

Location

United States

Related Subject Headings

  • Sulfhydryl Compounds
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • S-Nitrosothiols
  • S-Nitrosoglutathione
  • Oxygenases
  • Oxidative Stress
  • Nitrosation
  • Nitric Oxide
  • Hemeproteins
 

Citation

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Foster, M. W., Liu, L., Zeng, M., Hess, D. T., & Stamler, J. S. (2009). A genetic analysis of nitrosative stress. Biochemistry, 48(4), 792–799. https://doi.org/10.1021/bi801813n
Foster, Matthew W., Limin Liu, Ming Zeng, Douglas T. Hess, and Jonathan S. Stamler. “A genetic analysis of nitrosative stress.Biochemistry 48, no. 4 (February 3, 2009): 792–99. https://doi.org/10.1021/bi801813n.
Foster MW, Liu L, Zeng M, Hess DT, Stamler JS. A genetic analysis of nitrosative stress. Biochemistry. 2009 Feb 3;48(4):792–9.
Foster, Matthew W., et al. “A genetic analysis of nitrosative stress.Biochemistry, vol. 48, no. 4, Feb. 2009, pp. 792–99. Pubmed, doi:10.1021/bi801813n.
Foster MW, Liu L, Zeng M, Hess DT, Stamler JS. A genetic analysis of nitrosative stress. Biochemistry. 2009 Feb 3;48(4):792–799.
Journal cover image

Published In

Biochemistry

DOI

EISSN

1520-4995

Publication Date

February 3, 2009

Volume

48

Issue

4

Start / End Page

792 / 799

Location

United States

Related Subject Headings

  • Sulfhydryl Compounds
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • S-Nitrosothiols
  • S-Nitrosoglutathione
  • Oxygenases
  • Oxidative Stress
  • Nitrosation
  • Nitric Oxide
  • Hemeproteins