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Nitric Oxide from commensal bacteria protects intestinal epithelial cells from apoptosis by protein S‐nitrosylation
Author(s) -
Kwon Young Man,
Neish Andrew Scott
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.570.17
Subject(s) - microbiology and biotechnology , nitric oxide , bacteria , s nitrosylation , apoptosis , biology , nitrosylation , signal transduction , intestinal epithelium , epithelium , chemistry , biochemistry , enzyme , genetics , cysteine , endocrinology
Commensal bacteria mediate a variety of homeostatic effects on the gut epithelium and may protect mucosal surfaces against pathogens and other potentially injurious stimuli. How commensal bacterial mediate these function are not known. Nitric oxide (NO) is small molecule involved in many signaling pathways that acts by post‐translational modification (S‐nitrosylation) of regulatory proteins and has been shown to have anti‐apoptotic (or immunomodulatory) effects. We demonstrate that most strains of commensal bacteria produce NO, and this NO is efficiently transferred into cultured model epithelia. Transfer of NO is increased when the bacteria and epithelia are cocultured in presence of exogenous nitrate. In model epithelia colonized with commensal bacterial strains, we observed S‐nitrosylation of thioredoxin1, which has redox regulatory and anti‐apoptotic functions, and the key apoptotic signaling intermediates, ASK1 and JNK. As expected, this modification resulted in the functional inactivation of the pro‐apoptotic JNK pathway, and accordingly, commensal treated cells were resistant to exogenous proapoptotic stimuli. These observations suggest that the S‐nitrosylation of these proteins in epithelia by NO produced by commensal bacteria increases survival of intestinal cells, and explain how epithelial mucosa can show tolerance to environmental stresses.