Bisindoylmaleimide I suppresses adipocyte differentiation through stabilization of intracellular beta-catenin protein.
The Wnt/beta-catenin signaling pathway plays important roles in cell differentiation. Activation of this pathway, likely by Wnt-10b, has been shown to inhibit adipogenesis in cultured 3T3-L1 preadipocytes and mice. Here we revealed that bisindoylmaleimide I (BIM), which is widely used as a specific inhibitor of protein kinase C (PKC), inhibits adipocyte differentiation through activation of the Wnt/beta-catenin signaling pathway. BIM increased beta-catenin responsive transcription (CRT) and up-regulated intracellular beta-catenin levels in HEK293 cells and 3T3-L1 preadipocytes. BIM significantly decreased intracellular lipid accumulation and reduced expression of important adipocyte marker genes including peroxisome-proliferator-activated receptor gamma (PPARgamma) and CAATT enhancer-binding protein alpha (C/EBPalpha) in 3T3-L1 preadipocytes. Taken together, our findings indicate that BIM inhibits adipogenesis by increasing the stability of beta-catenin protein in 3T3-L1 preadipocyte cells.
Cho
Munju
M
PharmacoGenomics Research Center, Inje University, Busan 614-735, Republic of Korea.
Park
Seoyoung
S
Gwak
Jungsug
J
Kim
Dong-Eun
DE
Yea
Sung Su
SS
Shin
Jae-Gook
JG
Oh
Sangtaek
S
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D047495:PPAR gamma; D051153:Wnt Proteins; D051176:beta Catenin; D011493:Protein Kinase C; C070515:bisindolylmaleimide I