Format

Send to

Choose Destination
J Proteome Res. 2014 Nov 7;13(11):4942-58. doi: 10.1021/pr5002675. Epub 2014 Aug 4.

Decoding the s-nitrosoproteomic atlas in individualized human colorectal cancer tissues using a label-free quantitation strategy.

Author information

1
Institute of Chemistry, Academia Sinica , Taipei, Taiwan.

Abstract

The abnormal S-nitrosylation induced by the overexpression and activation of inducible nitric oxide synthase (iNOS) modulates many human diseases, such as inflammation and cancer. To delineate the pathophysiological S-nitrosoproteome in cancer patients, we report an individualized S-nitrosoproteomic strategy with a label-free method for the site-specific quantification of S-nitrosylation in paired tumor and adjacent normal tissues from 11 patients with colorectal cancer (CRC). This study provides not only the first endogenous human S-nitrosoproteomic atlas but also the first individualized human tissue analysis, identifying 174 S-nitrosylation sites in 94 proteins. Fourteen novel S-nitrosylation sites with a high frequency of elevated levels in 11 individual patients were identified. An individualized S-nitrosylation quantitation analysis revealed that the detected changes in S-nitrosylation were regulated by both the expression level and the more dramatic post-translational S-nitrosylation of the targeted proteins, such as thioredoxin, annexin A4, and peroxiredoxin-4. These endogenous S-nitrosylated proteins illustrate the network of inflammation/cancer-related and redox reactions mediated by various S-nitrosylation sources, including iNOS, transnitrosylase, or iron-sulfur centers. Given the demonstrated sensitivity of individualized tissue analysis, this label-free approach may facilitate the study of the vastly under-represented S-nitrosoproteome and enable a better understanding of the effect of endogenous S-nitrosylation in cancer.

KEYWORDS:

S-nitrosylation; biotin switch; colorectal cancer; label-free quantitation

PMID:
25040305
DOI:
10.1021/pr5002675
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center