Upregulation of heme oxygenase-1 by Epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways

摘要: Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated by various phytochemicals and we examined the ability of Epigallocatechin-3-gallate (EGCG), major constituent green tea, to upregulate HO-1 expression in endothelial cells (ECs). We demonstrate that EGCG induces concentration- time-dependent manner. Furthermore, EGCG-mediated induction was abrogated presence actinomycin D cycloheximide, indicating this upregulation occurred at transcriptional level. also upregulates Nrf2 levels nuclear extracts increases ARE-luciferase activity. most potent inducer different tea constituents analyzed, but had no detectable cytotoxic effects over 25-100 microM dosage range. The inhibition intracellular ROS production N-acetylcysteine (NAC), glutathione (GSH), superoxide dismutase (SOD), catalase mitochondrial complex I inhibitor, rotenone, results decrease EGCG-dependent expression. In addition, determined tyrosine kinase involved as genistein. ECs treated with exhibit activation Akt ERK1/2. pharmacological inhibitors phosphatidylinositol 3-kinase MEK1/2, which are upstream ERK1/2, respectively, attenuate EGCG-induced On other hand, pretreatment these exerts significant against H2O2, suggesting an important component protection oxidative stress. Hence, novel phytochemical further identify principal underlying mechanisms process.