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

Rushworth, S. A., Ogborne, R. M., Charalambos, C. A. and O'Connell, M. A. (2006) Role of protein kinase C delta in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochemical and Biophysical Research Communications, 341 (4). pp. 1007-1016. ISSN 0006-291X

Full text not available from this repository. (Request a copy)

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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
University of East Anglia > Faculty of Science > Research Groups > Pharmaceutical Cell Biology
Depositing User: Rachel Smith
Date Deposited: 02 Jun 2011 16:46
Last Modified: 23 Aug 2018 10:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/31792
DOI: 10.1016/j.bbrc.2006.01.065

Actions (login required)

View Item