Bisphenol A Downregulates Akt Signaling and Inhibits Adiponectin Production and Secretion in 3T3-L1 Adipocytes
Bisphenol A Downregulates Akt Signaling and Inhibits Adiponectin Production and Secretion in 3T3-L1 Adipocytes
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DOI：
10.5551/jat.4051
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发表时间：
2010-01-01
影响因子：
4.4
通讯作者：
Masuno, Hiroshi
中科院分区：
文献类型：
--
作者：
Kidani, Teruki;Kamei, Setsuya;Masuno, Hiroshi
目的：本研究旨在探讨环境内分泌干扰化学物质双酚A （BPA）及其相关化学物质是否影响3T3-L1脂肪细胞中脂联素的产生和分泌，以及BPA是否通过Akt信号通路起作用。方法：用不同浓度（20 ~ 80 μ M）双酚a在无血清培养基中处理3T3-L1脂肪细胞24 h。介质通过0.2 μ m过滤器过滤。用脂联素酶联免疫试剂盒测定细胞匀浆和培养基中的脂联素。用Western blot方法分析80 μ M双酚a处理24 h后Akt和p-Akt的表达水平。结果：对照培养（即处理24 h不含BPA）细胞中脂联素DNA含量为49.4 μ g/mg，向培养基中分泌的脂联素DNA含量为35.5 μ g/mg。与对照组相比，80 μ M双酚a可使细胞内脂联素和培养液中脂联素含量分别降低60% （p < 0.01）和56% (p < 0.01)，使Akt和p-Akt水平分别降低46% （p < 0.01）和29% （p < 0.01）。与双酚a一样，双酚F （BPF）、双酚E （BPE）和双酚B （BPB）降低了细胞内和培养基脂联素的含量。降低细胞内脂联素量的潜力大小依次为BPB > BPA > BPE > BPF。结论：BPA下调Akt信号通路，抑制3T3-L1脂肪细胞脂联素的产生和分泌。
Aim: The aim of this study was to investigate whether environmental endocrine-disrupting chemicals, bisphenol A (BPA) and BPA-related chemicals, affect adiponectin production and secretion in 3T3-L1 adipocytes and whether BPA acts through Akt signaling.Methods: 3T3-L1 adipocytes were treated for 24 h with BPA at various concentrations (20-80 mu M) in serum-deprived medium. The medium was filtered through a 0.2 mu m filter. Adiponectin in the in-franatants of cell homogenates and in the media was measured using an adiponectin ELISA kit. The levels of Akt and p-Akt in cultures treated for 24 h with or without 80 mu M BPA were analyzed by Western blot.Results: The control cultures (i.e., BPA was absent during a 24-h treatment period) contained 49.4 mu g/mg DNA of adiponectin in the cells and secreted 35.5 mu g/mg DNA of adiponectin into the medium. BPA at 80 mu M dose-dependently decreased the amounts of intracellular and medium adiponectin by 60% (p < 0.01) and 56% (p < 0.01), respectively, and decreased the levels of Akt and p-Akt by 46% (p < 0.01) and 29% (p < 0.01), respectively, compared with the control cultures. Like BPA, bisphenol F (BPF), bisphenol E (BPE), and bisphenol B (BPB) decreased the amounts of intracellular and medium adiponectin. The order of the potential to decrease the amount of intracellular adiponectin was BPB > BPA > BPE > BPF.Conclusions: BPA downregulates Akt signaling and inhibits adiponectin production and secretion in 3T3-L1 adipocytes.