title: (-)-Epigallocatechin-3-gallate enhances the expression of an insulin-inducible transcription factor gene via a phosphoinositide 3-kinase/atypical protein kinase C lambda pathway.
abstract: 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.
authors.affiliation: Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Asano
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takagi
authors.forename: Ayumi
authors.initials: A
authors.lastname: Haneishi
authors.forename: Taichi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tamio
authors.initials: T
authors.lastname: Noguchi
authors.forename: Soichiro
authors.initials: S
authors.lastname: Nakamura
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008113:Liver Neoplasms; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D000099293:Protein Kinase C-lambda
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002392:Catechin; D004791:Enzyme Inhibitors; D007328:Insulin; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D012333:RNA, Messenger; D000099293:Protein Kinase C-lambda; C109509:Bhlhe41 protein, rat; C045651:epigallocatechin gallate