Cho Munju, Park Seoyoung, Gwak Jungsug, Kim Dong-Eun, Yea Sung Su, Shin Jae-Gook, Oh Sangtaek
PharmacoGenomics Research Center, Inje University, Busan 614-735, Republic of Korea.
Biochem Biophys Res Commun. 2008 Feb 29;367(1):195-200. doi: 10.1016/j.bbrc.2007.12.147. Epub 2008 Jan 2.
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.
Wnt/β-连环蛋白信号通路在细胞分化中发挥重要作用。该通路的激活，可能是由Wnt-10b介导，已被证明在培养的3T3-L1前脂肪细胞和小鼠中抑制脂肪生成。在此我们揭示，双吲哚马来酰亚胺I（BIM），一种广泛用作蛋白激酶C（PKC）特异性抑制剂的物质，通过激活Wnt/β-连环蛋白信号通路来抑制脂肪细胞分化。BIM在HEK293细胞和3T3-L1前脂肪细胞中增加了β-连环蛋白反应性转录（CRT）并上调了细胞内β-连环蛋白水平。BIM显著降低了3T3-L1前脂肪细胞内的脂质积累，并减少了包括过氧化物酶体增殖物激活受体γ（PPARγ）和CCAAT增强子结合蛋白α（C/EBPα）在内的重要脂肪细胞标记基因的表达。综上所述，我们的研究结果表明，BIM通过增加3T3-L1前脂肪细胞中β-连环蛋白的稳定性来抑制脂肪生成。
