Atypical PKCζ transduces electrophilic fatty acid signaling in pulmonary epithelial cells

Chang Jiang Guo, Francisco J. Schopfer, Linda Gonzales, Ping Wang, Bruce A. Freeman, Andrew J. Gow

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Nitric oxide and secondary oxides of nitrogen react with unsaturated fatty acids such as linoleic acid to yield oxidized and nitrated products. Fatty acid nitroalkene derivatives, (e.g. nitrolinoleate [LNO 2]) are produced by oxidative inflammatory reactions, detected clinically, display potent electrophilic reactivity and induce post-translational protein modifications that mediate adaptive inflammatory signaling responses. LNO 2 signaling was examined in lung epithelial cells because the alveolar compartment is a rich site for the transduction of redox and inflammatory reactions. LNO 2 did not directly induce Ca 2+ influx in cultured lung epithelial cells, but inhibited bradykinin-induced Ca 2+ influx in a cGMP-independent manner. In contrast, LNO 2 activated MAP kinase (Erk1/2) by a mechanism independent of bradykinin. It was hypothesized that these unique responses were transduced by activation of different protein kinase C isotypes, supported by the observation that LNO 2-mediated inhibition of Ca 2+ influx was blocked by the non-selective PKC inhibitors chelerythine chloride and calphostin C, but not by the calcium dependent "classic" PKC inhibitor Gö6976. Western blot analysis showed that atypical PKCζ was activated by LNO 2 stimulation, with PKCζ and Erk activation also demonstrated in primary culture of human lung type II cells. Addition of pseudotypical PKCζ substrate peptide reversed LNO 2-mediated induction of Ca 2+ influx and MAP kinase activation. Finally, the electrophilic nature of LNO 2 resulted in a novel mode of PKCζ activation, covalent adduction of the enzyme. In summary, LNO 2 mediated signaling in lung type II epithelial cells occurs via a unique pathway involving PKCζ.

Original languageEnglish
Pages (from-to)366-372
Number of pages7
JournalNitric Oxide - Biology and Chemistry
Issue number3
Publication statusPublished - 30 Oct 2011
Externally publishedYes


  • Calcium mobilization
  • Nitrated lipids
  • Protein kinase C
  • Pulmonary epithelial cell
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cancer Research
  • Physiology

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