Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 373, Issue 4, Pages 584-588Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.06.068
Keywords
epigallocatechin; haem oxygenase-1; monocytic cells; Nrf2; protein kinase C; green tea polyphenols
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Funding
- Medical Research Council [MC_U105960399] Funding Source: Medline
- MRC [MC_U105960399] Funding Source: UKRI
- Medical Research Council [MC_U105960399] Funding Source: researchfish
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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 PKC alpha beta and delta in THP-1 cells. PKC delta inhibition significantly decreased EGC-induced HO-1 mRNA expression, whereas PKC alpha- and beta-specific inhibitors had no significant effect. These results demonstrate for the first time that EGC-induced HO-1 expression occurs via PKC delta and Nrf2. (C) 2008 Elsevier Inc. All rights reserved.
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