title: Green tea (-)-epigallocatechin gallate inhibits IGF-I and IGF-II stimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor, but not AMP-activated protein kinase pathway.
abstract: METHODS
  This study investigated the pathways involved in epigallocatechin gallate (EGCG) modulation of insulin-like growth factor (IGF)-I-stimulated and IGF-II-stimulated mitogenesis in 3T3-L1 preadipocytes.
  
  
  RESULTS
  We found that this process was dose and time dependent, and caused by suppression of IGF-I-stimulated and IGF-II-stimulated phosphorylation of p66Shc and mitogen-activated protein kinase (MAPK) pathway proteins, including MEK1 kinase (RAF1), extracellular signal-regulated protein kinase (ERK) kinase (MEK1), and ERK 1 and ERK 2 (ERK1/2), but not phospho-Jun-N-terminal kinase, protein kinase B, p52Shc, or p46Shc. Furthermore, EGCG inhibited the IGF-I-stimulated phosphorylation of the IGF-I receptor-beta (IGF-IR β), the association of IGF-IR with the p66Shc protein, and the IGF-II-stimulated associations of the IGF-II receptor with G(αi-2) and p66Shc proteins, suggesting that EGCG selectively affects particular types of Shc and MAPK family members. Pretreatment with antiserum against the EGCG receptor (also known as the 67-kDa laminin receptor; 67LR), but not with an adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, prevented the inhibitory actions of EGCG on IGF-I- and IGF-II-stimulated ERK1/2 phosphorylation and subsequent preadipocyte proliferation.
  
  
  CONCLUSIONS
  The results of this study suggest that EGCG mediates anti-IGF-I and anti-IGF-II signals in preadipocyte mitogenesis via the 67LR but not the AMPK pathway.
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taiwan.
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Ku
authors.forename: Hang-Seng
authors.initials: HS
authors.lastname: Liu
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Hung
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Chen
authors.forename: Hsien-Chun
authors.initials: HC
authors.lastname: Liu
authors.forename: Hsin-Huei
authors.initials: HH
authors.lastname: Chang
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Tsuei
authors.forename: Li-Jane
authors.initials: LJ
authors.lastname: Shih
authors.forename: Ching-Ling
authors.initials: CL
authors.lastname: Lin
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Lin
authors.forename: Yung-Hsi
authors.initials: YH
authors.lastname: Kao
mesh_terms: D041721:3T3-L1 Cells; D000249:Adenosine Monophosphate / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D047468:Immunoprecipitation; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D017474:Receptors, Laminin / Q000378:metabolism*; D013662:Tea / Q000737:chemistry
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D017527:Receptor, IGF Type 2; D017474:Receptors, Laminin; D013662:Tea; D000249:Adenosine Monophosphate; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D002392:Catechin; C045651:epigallocatechin gallate; D017526:Receptor, IGF Type 1; D020928:Mitogen-Activated Protein Kinases