(−)-Epigallocatechin-3-gallate Enhances the Expression of an Insulin-Inducible Transcription Factor Gene via a Phosphoinositide 3-Kinase/Atypical Protein Kinase C Lambda Pathway

• Published in: Journal of agricultural and food chemistry 2011-12, Vol.59 (24), p.13360-13364
• Main Authors: Asano, Kosuke, Takagi, Katsuhiro, Haneishi, Ayumi, Yamamoto, Taichi, Tanaka, Takashi, Noguchi, Tamio, Nakamura, Soichiro, Yamada, Kazuya
• Format: Article
• Language: English
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Biological and medical sciences; Catechin - analogs & derivatives; Catechin - pharmacology; Cell Line, Tumor; Enzyme Inhibitors - pharmacology; Food industries; Fundamental and applied biological sciences. Psychology; gene expression; Gene Expression - drug effects; genes; green tea; Insulin - pharmacology; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; liver; Liver Neoplasms; messenger RNA; Molecular Nutrition; phosphatidylinositol 3-kinase; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; phosphorylation; protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Rats; RNA, Messenger - analysis; signal transduction; Signal Transduction - physiology; transcription (genetics); transcription factors; Western blotting
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf204016k

The rat enhancer of split- and hairy-related protein-1 (SHARP-1) is an insulin-inducible transcriptional repressor. In this study, we examined issues of whether (−)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, regulates the expression of the rat SHARP-1 gene and which signaling pathway mediates the regulation. When H4IIE cells were treated with EGCG, SHARP-1 mRNA levels rapidly increased. Pretreatments with inhibitors for either phosphoinositide 3-kinase (PI 3-K) or protein kinase C partially blocked EGCG induction. Atypical protein kinase C lambda (aPKCλ) is known as a downstream target of PI 3-K in the liver. When a dominant–negative form of aPKCλ was expressed, the EGCG-induced SHARP-1 mRNAs was inhibited. Finally, Western blot analysis revealed that EGCG rapidly and temporarily stimulates aPKCλ phosphorylation. Thus, we conclude that EGCG induces SHARP-1 gene expression via a PI 3-K/aPKCλ signaling pathway.