Epigallocatechin activates haem oxygenase-1 expression via protein kinase Cdelta and Nrf2.
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 PKCalphabeta and delta in THP-1 cells. PKCdelta inhibition significantly decreased EGC-induced HO-1 mRNA expression, whereas PKCalpha- and beta-specific inhibitors had no significant effect. These results demonstrate for the first time that EGC-induced HO-1 expression occurs via PKCdelta and Nrf2.
Ogborne
Richard M
RM
MRC Human Nutrition Research, Fulbourn Road, Cambridge CB1 9NL, UK.
Rushworth
Stuart A
SA
O'Connell
Maria A
MA
D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002392:Catechin; D051547:Heme Oxygenase-1; D051745:Protein Kinase C-delta; C057580:gallocatechol