Effects of 1,1,1-trichloro-2,2-bis (p-chlorophenyl)-ethane (p,p′-DDT) on 3T3-L1 and 3T3-F442A adipocyte differentiation
Effects of 1,1,1-trichloro-2,2-bis (p-chlorophenyl)-ethane (p,p′-DDT) on 3T3-L1 and 3T3-F442A adipocyte differentiation
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DOI：
10.1016/s0006-2952(01)00933-9
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发表时间：
2002-03-01
影响因子：
5.8
通讯作者：
Matsumura, F
中科院分区：
文献类型：
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作者：
Moreno-Aliaga, MJ;Matsumura, F
基于我们最初观察到的1,1,1-三氯-2,2-二（对氯苯基）-乙烷（p,p'-DDT）诱导3T3-L1脂肪细胞分化的浓度依赖性增加，我们以3T3-L1和3T3-F442A细胞为研究对象，研究了p，p'-DDT诱导脂肪细胞分化的机制。由于已知3T3-L1脂肪细胞系的分化涉及转录因子CCAAT增强子结合蛋白β (C/EBPbeta)，过氧化物酶体增殖物激活受体γ (PPARgamma)和C/EBPalpha的诱导，因此必须研究这些因子在p，p'- ddt诱导的脂肪细胞分化中的可能作用。结果发现，p,p'- ddt处理的3T3-L1细胞显示PPARgamma和C/EBPalpha蛋白的核水平呈浓度依赖性增加。另一方面，p,p'-DDT （20mum）处理未影响分化过程中C/EBP蛋白的表达模式。结合DNA C/EBP识别位点的核蛋白凝胶移位分析显示，p,p'- ddt处理的细胞在分化第2天的结合活性增加。Supershift分析显示，这种上升主要是由C/EBPalpha-DNA复合物丰度的急剧增加引起的。在诱导分化后第4天和第7天，也观察到类似的增加。肿瘤坏死因子a对脂肪细胞分化的抑制作用较强，与PPARgamma的激活剂曲格列酮共同作用逆转，p,p'-DDT不能逆转肿瘤坏死因子x对3T3-L1细胞脂肪细胞分化的抑制作用。3T3-F442A是另一种在胰岛素和胎牛血清存在下可诱导分化为脂肪细胞的前脂肪细胞系。p,p'-DDT （20mum）在诱导分化后第2天诱导细胞形态发生改变。然而，这些细胞不能成为完全分化的脂肪细胞。因此，这些数据表明，p,p'-DDT能够通过修饰调节这一事件的转录因子来改变脂肪细胞系的分化过程。(C) 2002爱思唯尔科学有限公司版权所有。
Based upon our initial observations that 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (p,p'-DDT) induces a concentration-dependent increase in 3T3-L1 adipocyte differentiation, the mechanism of the p,p'-DDT-induced adipocyte differentiation was studied, using 3T3-L1 and 3T3-F442A cells. Since, it is known that the differentiation of the 3T3-L1 adipocyte cell line involves the induction of the transcription factors CCAAT enhancer binding protein beta (C/EBPbeta), peroxisome proliferator-activated receptor gamma (PPARgamma), and C/EBPalpha the possible role of these factors in p,p'-DDT-induced adipocyte differentiation had to be examined. It was found that p,p'-DDT-treated 3T3-L1 cells showed a concentration-dependent increase in the nuclear levels of both PPARgamma and C/EBPalpha protein. On the other hand, treatment with p,p'-DDT (20 muM) did not affect the expression pattern of C/EBP protein during differentiation. Gel shift analysis of nuclear proteins for binding to the C/EBP recognition site of DNA showed an increase in binding activity at day 2 of differentiation in p,p'-DDT-treated cells. Supershift analysis revealed that this rise was caused mainly by a dramatic increase in the abundance of the C/EBPalpha-DNA complex. Similar increases were observed at days 4 and 7 after the induction of differentiation. Tumor necrosis factor a induced a strong inhibition of adipocyte differentiation, which was reversed by co-treatment with troglitazone, an activator of PPARgamma, p,p'-DDT was unable to reverse the inhibitory effect of tumor necrosis factor x on adipocyte differentiation in 3T3-L1 cells. 3T3-F442A is another preadipocyte cell line that can be induced to differentiate into adipocytes in the presence of insulin and fetal bovine serum. p,p'-DDT (20 muM) induced an alteration in the morphology of these cells at day 2 after the induction of differentiation. These cells however, were unable to become fully differentiated adipocytes. These data showed, therefore, the ability of p,p'-DDT to alter the differentiation process of adipocyte cell lines through the modification of transcription factors regulating this event. (C) 2002 Elsevier Science Inc. All rights reserved.