PGD(2) and PGE(2) regulate gene expression of Prx 6 in primary macrophages via Nrf2

S.F. Erttmann, A. Bast, J. Seidel, K. Breitbach, R. Walther, I. Steinmetz

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

Peroxiredoxin 6 (Prx 6) is a bifunctional enzyme with both glutathione peroxidase and acidic Ca(2+)-independent phospholipase A(2) activities. We have recently shown that exposure of murine bone marrow-derived macrophages to LPS and IFN-gamma leads to induction of COX-2 expression and secretion of PGE(2), up-regulating Prx 6 mRNA levels. This study was designed to investigate various prostaglandins (PGs) for their ability to induce gene expression of Prxs, in particular Prx 6, and to determine the underlying regulatory mechanisms. We provide evidence that both conventional and cyclopentenone PGs enhance Prx 6 mRNA expression. Treatment with either activators or inhibitors of adenylate cyclase as well as cAMP analogs indicated that Prx 6 gene expression is regulated by adenylate cyclase in response to PGD(2) or PGE(2). Furthermore, our study revealed that JAK2, PI3K, PKC, and p38 MAPK contribute to the PGD(2)- or PGE(2)-dependent Prx 6 induction. Using stimulated macrophages from Nrf2-deficient mice or activators of Nrf2 and PPARgamma, we found that Nrf2, but not PPARgamma, is involved in the PG-dependent increase in Prx 6 mRNA expression. In summary, our data suggest multiple signaling pathways of Prx 6 regulation by PGs and identified Nrf2 as a critical player mediating transcriptional induction.
Original languageEnglish
Pages (from-to)626-640
Number of pages15
JournalFree Radical Biology and Medicine
Volume51
Issue number3
DOIs
Publication statusPublished - 1 Aug 2011

Keywords

  • Adenylate cyclase
  • JAK2
  • Macrophage
  • MAPK
  • Nrf2
  • Peroxiredoxin
  • PI3K
  • PKC
  • Prostaglandin
  • Free radicals
  • 1-CYS PEROXIREDOXIN EXPRESSION
  • ANTIOXIDANT RESPONSE ELEMENT
  • LUNG EPITHELIAL-CELLS
  • OXIDATIVE STRESS
  • HEME OXYGENASE-1
  • GLUTATHIONE-PEROXIDASE
  • PHOSPHOLIPASE A(2)
  • TRANSCRIPTIONAL REGULATION
  • MAMMALIAN PEROXIREDOXIN
  • DIFFERENTIAL REGULATION

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