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Proteomic characterization of the cellular response to nitrosative stress mediated by s-nitrosoglutathione reductase inhibition.

Publication ,  Journal Article
Foster, MW; Yang, Z; Gooden, DM; Thompson, JW; Ball, CH; Turner, ME; Hou, Y; Pi, J; Moseley, MA; Que, LG
Published in: J Proteome Res
April 6, 2012

The S-nitrosoglutathione-metabolizing enzyme, GSNO reductase (GSNOR), has emerged as an important regulator of protein S-nitrosylation. GSNOR ablation is protective in models of asthma and heart failure, raising the idea that GSNOR inhibitors might hold therapeutic value. Here, we investigated the effects of a small molecule inhibitor of GSNOR (GSNORi) in mouse RAW 264.7 macrophages. We found that GSNORi increased protein S-nitrosylation in cytokine-stimulated cells, and we utilized stable isotope labeling of amino acids in cell culture (SILAC) to quantify the cellular response to this "nitrosative stress". The expression of several cytokine-inducible immunomodulators, including osteopontin, cyclooxygenase-2, and nitric oxide synthase isoform 2 (NOS2), were decreased by GSNORi. In addition, selective targets of the redox-regulated transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-including heme oxygenase 1 (HO-1) and glutamate cysteine ligase modulatory subunit-were induced by GSNORi in a NOS2- and Nrf2-dependent manner. In cytokine-stimulated cells, Nrf2 protected from GSNORi-induced glutathione depletion and cytotoxicity and HO-1 activity was required for down-regulation of NOS2. Interestingly, GSNORi also affected a marked increase in NOS2 protein stability. Collectively, these data provide the most complete description of the global effects of GSNOR inhibition and demonstrate several important mechanisms for inducible response to GSNORi-mediated nitrosative stress.

Duke Scholars

Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

April 6, 2012

Volume

11

Issue

4

Start / End Page

2480 / 2491

Location

United States

Related Subject Headings

  • Stress, Physiological
  • S-Nitrosoglutathione
  • Proteome
  • Nitrosation
  • Nitric Oxide Synthase Type II
  • NF-E2-Related Factor 2
  • Mice
  • Macrophages
  • Isotope Labeling
  • Heme Oxygenase (Decyclizing)
 

Citation

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Foster, M. W., Yang, Z., Gooden, D. M., Thompson, J. W., Ball, C. H., Turner, M. E., … Que, L. G. (2012). Proteomic characterization of the cellular response to nitrosative stress mediated by s-nitrosoglutathione reductase inhibition. J Proteome Res, 11(4), 2480–2491. https://doi.org/10.1021/pr201180m
Foster, Matthew W., Zhonghui Yang, David M. Gooden, J Will Thompson, Carol H. Ball, Meredith E. Turner, Yongyong Hou, Jingbo Pi, M Arthur Moseley, and Loretta G. Que. “Proteomic characterization of the cellular response to nitrosative stress mediated by s-nitrosoglutathione reductase inhibition.J Proteome Res 11, no. 4 (April 6, 2012): 2480–91. https://doi.org/10.1021/pr201180m.
Foster MW, Yang Z, Gooden DM, Thompson JW, Ball CH, Turner ME, et al. Proteomic characterization of the cellular response to nitrosative stress mediated by s-nitrosoglutathione reductase inhibition. J Proteome Res. 2012 Apr 6;11(4):2480–91.
Foster, Matthew W., et al. “Proteomic characterization of the cellular response to nitrosative stress mediated by s-nitrosoglutathione reductase inhibition.J Proteome Res, vol. 11, no. 4, Apr. 2012, pp. 2480–91. Pubmed, doi:10.1021/pr201180m.
Foster MW, Yang Z, Gooden DM, Thompson JW, Ball CH, Turner ME, Hou Y, Pi J, Moseley MA, Que LG. Proteomic characterization of the cellular response to nitrosative stress mediated by s-nitrosoglutathione reductase inhibition. J Proteome Res. 2012 Apr 6;11(4):2480–2491.
Journal cover image

Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

April 6, 2012

Volume

11

Issue

4

Start / End Page

2480 / 2491

Location

United States

Related Subject Headings

  • Stress, Physiological
  • S-Nitrosoglutathione
  • Proteome
  • Nitrosation
  • Nitric Oxide Synthase Type II
  • NF-E2-Related Factor 2
  • Mice
  • Macrophages
  • Isotope Labeling
  • Heme Oxygenase (Decyclizing)