Role of protein kinase C delta in curcumin-induced antioxidant response element-mediated gene expression in human monocytes

S. A. Rushworth, R. M. Ogborne, C. A. Charalambos, M. A. O'Connell

Research output: Contribution to journalArticlepeer-review

142 Citations (Scopus)

Abstract

The Nrf2/antioxidant response element (ARE) signaling pathway plays a key role in activating cellular antioxidants, including heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase-1 (NQO1), and glutathione. Protein kinase C (PKC) may also regulate these antioxidants, as PKC phosphorylates Nrf2 in vitro. This study examined the role of PKC in ARE-mediated gene regulation in human monocytes by curcumin, a potent inducer of the Nrf2/ARE pathway. Curcumin increased HO-1 and glutamyl cysteine ligase modulator (GCLM) expression and stimulated Nrf2 binding to the ARE. Curcumin also rapidly stimulated PKC phosphorylation and Ro-318220, a pan-PKC inhibitor, decreased curcumin-induced GCLM and HO-1 mRNA expression and ARE binding. Rottlerin (a PKC 6 inhibitor) and PKC 6 antisense oligonucleotides significantly inhibited curcumin-induced GCLM and HO-1 mRNA expression and ARE binding. Furthermore, a p38 MAP kinase inhibitor reduced GCLM and HO-1 expression and rottlerin inhibited curcumin-induced p38 phosphorylation. In summary, curcumin activates ARE-mediated gene expression in human monocytes via PKC 6, upstream of p38 and Nrf2. (c) 2006 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)1007-1016
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume341
Issue number4
DOIs
Publication statusPublished - 2006

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