CCAAT/ENHANCER BINDING-PROTEIN-ALPHA IS SUFFICIENT TO INITIATE THE 3T3-L1 ADIPOCYTE DIFFERENTIATION PROGRAM

CCAAT/ENHANCER BINDING-PROTEIN-ALPHA IS SUFFICIENT TO INITIATE THE 3T3-L1 ADIPOCYTE DIFFERENTIATION PROGRAM
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DOI:
10.1073/pnas.91.19.8757
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发表时间:
1994-09-13
影响因子:
11.1
通讯作者:
LANE, MD
LANE, MD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LIN, FT;LANE, MD

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既往研究表明外源性激素诱导3T3-L1前脂肪细胞分化需要CCAAT/增强子结合蛋白α (C/EBP α)。然而,无法确定C/EBP α是否足以诱导分化,因为其抗噬活性阻止了高水平表达C/EBP α的3T3-L1细胞系的繁殖。通过使用异丙基β - d -硫代半乳糖苷(IPTG)诱导的p42 C/EBP α表达载体系统稳定转染3T3-L1前脂肪细胞,解决了这个问题。iptg诱导的C/EBP α 42-kDa亚型在脂肪前细胞中的表达导致了几种内源性脂肪细胞特异性基因(编码422脂肪P2蛋白、葡萄糖转运蛋白4和C/EBP α的基因)的表达和细胞质甘油三酯的积累。因此,C/EBP α不仅是必要的,而且是充分的,可以在不使用外源性激素的情况下触发生长受阻的3T3-L1前脂肪细胞的分化。
Previous studies showed that CCAAT/enhancer binding protein alpha (C/EBP alpha) is required for differentiation of 3T3-L1 preadipocytes induced by exogenous hormonal agents. It was not possible to ascertain, however, whether C/EBP alpha alone is sufficient to induce differentiation because its antimitogenic activity precluded propagating 3T3-L1 cell lines that constitutively express C/EBP alpha at high levels. This problem was circumvented by using 3T3-L1 preadipocytes stably transfected with an isopropyl beta-D-thiogalactoside (IPTG)-inducible p42 C/EBP alpha expression vector system. IPTG-induced expression of the 42-kDa isoform of C/EBP alpha in preadipocytes caused expression of several endogenous adipocyte-specific genes (genes encoding the 422 adipose P2 protein, glucose transporter 4, and C/EBP alpha) and the accumulation of cytoplasmic triglyceride. Thus, C/EBP alpha is not only necessary but also is sufficient to trigger differentiation of growth-arrested 3T3-L1 preadipocytes without use of exogenous hormonal agents.