(−)-Epigallocatechin-3-gallate stimulates both AMP-activated protein kinase and nuclear factor-kappa B signaling pathways

Abstract: We previously reported that (−)-epigallocatechin-3-gallate (EGCG) increased the level of SHARP-1 mRNA via a phosphoinositide 3-kinase/atypical protein kinase C lambda signaling pathway in rat H4IIE hepatoma cells. In the present study, we investigated other signaling pathway(s). Treating with either compound-C, BAY11-7082, or both, partially blocked the up-regulation of the SHARP-1 gene by EGCG. This suggests that AMP-activated protein kinase (AMPK)- and nuclear factor-kappa B (NF-κB)-signaling pathways were additively involved in the induction mediated by EGCG. Indeed, an AMPK activator induced a level of SHARP-1 mRNA. Although actinomycin D partially blocked the EGCG-induction of that SHARP-1 mRNA level, the nucleotide sequence between −1501 and −1 in the rat SHARP-1 gene did not positively respond to EGCG and NF-κB, respectively. Thus, we conclude that EGCG stimulates multiple signaling pathways in the SHARP-1 gene expression at the transcriptional and post-transcriptional levels and that there is no regulatory region susceptible to EGCG and NF-κB in the examined region. [Copyright &y& Elsevier]