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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

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

Published In Free Radic Biol Med, (2014 Feb)

Abstract: 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 5-25μM 9-NO or 10-NO for 6h 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.

PubMed ID: 24140437 Exiting the NIEHS site

MeSH Terms: Animals; Catalase/genetics; Catalase/metabolism; Caveolae/drug effects*; Caveolae/metabolism; Cell Line; Cyclooxygenase 2/genetics; Cyclooxygenase 2/metabolism; Dose-Response Relationship, Drug; Gene Expression Regulation/drug effects*; Glutathione Transferase/genetics; Glutathione Transferase/metabolism; HSP27 Heat-Shock Proteins/genetics; HSP27 Heat-Shock Proteins/metabolism; HSP70 Heat-Shock Proteins/genetics; HSP70 Heat-Shock Proteins/metabolism; Heme Oxygenase-1/genetics; Heme Oxygenase-1/metabolism; Isoenzymes/genetics; Isoenzymes/metabolism; Keratinocytes/cytology; Keratinocytes/drug effects*; Keratinocytes/metabolism; MAP Kinase Kinase 4/genetics; MAP Kinase Kinase 4/metabolism; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase 1/genetics; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/genetics; Mitogen-Activated Protein Kinase 3/metabolism; Oleic Acids/pharmacology*; Signal Transduction/drug effects*; Signal Transduction/genetics; p38 Mitogen-Activated Protein Kinases/genetics; p38 Mitogen-Activated Protein Kinases/metabolism

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