Epigallocatechin activates haem oxygenase-1 expression via protein kinase Cδ and Nrf2

Richard M. Ogborne, Stuart Rushworth, Maria O'Connell

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

The Nrf2/anti-oxidant response element (ARE) pathway plays an important role in regulating cellular anti-oxidants, including haem oxygenase-1 (HO-1). Various kinases have been implicated in the pathways leading to Nrf2 activation. Here, we investigated the effect of epigallocatechin (EGC) on ARE-mediated gene expression in human monocytic cells. EGC time and dose dependently increased HO-1 mRNA and protein expression but had minimal effect on expression of other ARE-regulated genes, including NAD(P)H:quinone oxidoreductase 1, glutathione cysteine ligase and ferritin. siRNA knock down of Nrf2 significantly inhibited EGC-induced HO-1 expression. Furthermore, inhibition of PKC by Ro-31-8220 dose dependently decreased EGC-induced HO-1 mRNA expression, whereas MAP kinase and phosphatidylinositol-3-kinase pathway inhibitors had no significant effect. EGC stimulated phosphorylation of PKCaß and d in THP-1 cells. PKCd inhibition significantly decreased EGC-induced HO-1 mRNA expression, whereas PKCa- and ß-specific inhibitors had no significant effect. These results demonstrate for the first time that EGC-induced HO-1 expression occurs via PKCd and Nrf2.
Original languageEnglish
Pages (from-to)584-588
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume373
Issue number4
DOIs
Publication statusPublished - 27 Jun 2008

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