Bisphenol A accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway
Bisphenol A accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway
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DOI：
10.1093/toxsci/kfi088
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发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Honda, K
中科院分区：
文献类型：
--
作者：
Masuno, H;Iwanami, J;Honda, K
为了鉴定双酚A（BPA）是否作为脂肪形成剂，在激素诱导分化成脂肪细胞后，用单独的BPA处理3 T3-L1细胞6天。BPA处理增加了培养物的三酰甘油（TG）含量，增加了培养物中油红O染色细胞的百分比，并增加了脂蛋白脂酶（LPL）和脂肪细胞特异性脂肪酸结合蛋白（aP 2）mRNA的水平。这些发现表明BPA能够加速3 T3-L1细胞向脂肪细胞的终末分化。磷脂酰肌醇3-激酶（PI 3-kinase）的化学抑制剂LY 294002可完全阻断BPA对TG积累和LPL及aP 2 mRNA表达的增加作用。Western blot分析显示BPA增加了磷酸化Akt激酶的水平。基于这些发现，我们得出结论，BPA通过PI 3-激酶和Akt激酶途径起作用，导致TG积累和脂肪细胞基因表达增加。研究了BPA相关化学品的构效关系。BPA的八种衍生物（三种在中心碳原子上具有不同取代基的二苯基烷烃，三种在酚环中的羟基上具有酯键的二苯基烷烃，一种在中心位置由硫原子组成的双酚，一种具有氰基而不是羟基的化学品，在酚环中）加速终末脂肪细胞分化，并且它们增加TG积累的效力是BPA的73-97%。羟基上具有醚键的两种二苯基烷烃和两种烷基酚（4-壬基酚和4-叔辛基酚）没有加速终末脂肪细胞分化的能力。
In order to identify whether bisphenol A (BPA) acts as an adipogenic agent, following the hormonal induction of differentiation into adipocytes, 3T3-L1 cells were treated for six days with BPA alone. Treatment with BPA increased the triacylglycerol (TG) content of the cultures, increased the percentage of Oil Red O-staining cells in the cultures, and increased the levels of lipoprotein lipase (LPL) and adipocyte-specific fatty acid binding protein (aP2) mRNAs. These findings indicate that BPA was able to accelerate terminal differentiation of 3T3-L1 cells into adipocytes. LY294002, a chemical inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), blocked completely the increasing effect of BPA on TG accumulation and expression of LPL and aP2 mRNAs. Western blot analysis revealed that BPA increased the level of phosphorylated Akt kinase. Based on these findings, we concluded that BPA acted through the PI 3-kinase and Akt kinase pathway, resulting in increased TG accumulation and expression of adipocyte genes. The structure-activity relationship for BPA-related chemicals was examined. Eight derivatives of BPA (three diphenylalkanes with different substituents at the central carbon atom, three diphenylalkanes with ester bonds on hydroxyl groups in the phenolic rings, one bisphenol consisting of a sulphur atom at the central position, one chemical with cyanic groups, instead of hydroxyl groups, in the phenolic rings) accelerated terminal adipocyte differentiation and their potencies to increase TG accumulation were 73-97% of that of BPA. Two diphenylalkanes with ether bonds on hydroxyl groups and two alkylphenols (4-nonylphenol and 4-tert-octylphenol) did not have the ability to accelerate terminal adipocyte differentiation.