Regulation of keratinocyte expression of stress proteins and antioxidants by the electrophilic nitrofatty acids 9- and 10-nitrooleic acid

Ruijin Zheng, Diane E. Heck, Adrienne T. Black, Andrew Gow, Debra L. Laskin, Jeffrey D. Laskin

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Nitric oxide and various by-products including nitrite contribute to tissue injury by forming novel intermediates via redox-mediated nitration reactions. Nitration of unsaturated fatty acids generates electrophilic nitrofatty acids such as 9-nitrooleic acid (9-NO) and 10-nitrooleic acid (10-NO), which are known to initiate intracellular signaling pathways. In these studies, we characterized nitrofatty acid-induced signaling and stress protein expression in mouse keratinocytes. Treatment of keratinocytes with 5-25 μM 9-NO or 10-NO for 6 h upregulated mRNA expression of heat shock proteins (hsp's) 27 and 70; primary antioxidants heme oxygenase-1 (HO-1) and catalase; secondary antioxidants glutathione S-transferase (GST) A1/2, GSTA3, and GSTA4; and Cox-2, a key enzyme in prostaglandin biosynthesis. The greatest responses were evident with HO-1, hsp27, and hsp70. In keratinocytes, 9-NO activated JNK and p38 MAP kinases. JNK inhibition suppressed 9-NO-induced HO-1, hsp27, and hsp70 mRNA and protein expression, whereas p38 MAP kinase inhibition suppressed HO-1. In contrast, inhibition of constitutive expression of Erk1/2 suppressed only hsp70, indicating that 9-NO modulates expression of stress proteins by distinct mechanisms. 9-NO and 10-NO also upregulated expression of caveolin-1, the major structural component of caveolae. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation revealed that HO-1, hsp27, and hsp70 were localized within caveolae after nitrofatty acid treatment of keratinocytes, suggesting a link between induction of stress response proteins and caveolin-1 expression. These data indicate that nitrofatty acids are effective signaling molecules in keratinocytes. Moreover, caveolae seem to be important in the localization of stress proteins in response to nitrofatty acids.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalFree Radical Biology and Medicine
Publication statusPublished - 2014
Externally publishedYes


  • Free radicals
  • Heat shock proteins
  • Heme oxygenase-1
  • Nitric oxide
  • Nitrooleic acid
  • Skin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)
  • Medicine(all)

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