Green tea (-)-epigallocatechin gallate inhibits IGF-I and IGF-IIstimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor, but not AMP-activated protein kinase pathway

Hui Chen Ku, Hang Seng Liu, Pei Fang Hung, Chia Lin Chen, Hsien Chun Liu, Hsin Huei Chang, Yi Wei Tsuei, Li Jane Shih, Ching Ling Lin, Chih Ming Lin, Yung Hsi Kao

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29 Scopus citations

Abstract

Scope: 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. Methods and 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, EGCGinhibited the IGF-I-stimulated phosphorylation of the IGF-I receptor-beta (IGF-IR β), the association of IGF-IRwith the p66Shc protein, and the IGF-II-stimulated associations of the IGF-IIreceptor with G αi-2 and p66Shc proteins, suggesting that EGCGselectively affects particular types of Shc and MAPKfamily members. Pretreatment with antiserum against the EGCGreceptor (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 EGCGon IGF-I- and IGF-II-stimulated ERK1/2 phosphorylation and subsequent preadipocyte proliferation. Conclusion: The results of this study suggest that EGCGmediates anti-IGF-I and anti-IGF-IIsignals in preadipocyte mitogenesis via the 67LR but not the AMPKpathway.

Original languageEnglish
Pages (from-to)580-592
Number of pages13
JournalMolecular Nutrition and Food Research
Volume56
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • Epigallocatechin gallate
  • Green tea
  • Insulin-like growth factor
  • Laminin receptor
  • Preadipocyte

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