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首页> 外文期刊>Journal of cellular biochemistry. >Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes.
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Down-modulation of erbB2 activity is necessary but not enough in the differentiation of 3T3-L1 preadipocytes.

机译：erbB2活性的下调是必需的，但不足以分化3T3-L1前脂肪细胞。

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The high incidence of obesity-related pathologies, led to the study of the mechanisms involved in preadipose cell proliferation and differentiation. Here, we demonstrate that modulation of erbB2, plays a fundamental role during proliferation and adipogenic induction of preadipocytes. Using 3T3-L1 cells as model, we demonstrate that EGF (10 nM, 5 min) in addition to stimulate receptor tyrosine phosphorylation of both erbB2 and EGFR, is able to induce the heterodimer erbB2-EGFR. We treated proliferating 3T3-L1 cells with two inhibitors, AG 825 (IC(50) 0.35 microM, 54 times more selective for erbB2 than for EGFR, IC(50) 19 microM), and AG 879 (IC(50) of 1 microM for erbB2 versus 500 microM for EGFR). We found that both inhibited the proliferation on a dose-dependent basis, reaching a 30% maximal inhibition at 100 microM (P < 0.001) for AG825, and a 20% maximal inhibition at 10 microM (P < 0.001) for AG 879. These results involve erbB2 in 3T3-L1 proliferation. When studying the differentiation process, we found that the action of MIX-Dexa immediately activates MEK, JNK and p38 kinases. We observed that PD98059 and SP600125 (MEK-ERK and JNK inhibitors, respectively) added 1 h prior to the MIX-Dexa induction produced a decrease in erbB2 expression after 6 h, which is even greater than the one produced by the inducers, MIX-Dexa. This work supports erbB2 as a key factor in 3T3-L1 adipogenesis, acting mostly and not only during the proliferative phase but also during the differentiation through modulation of both its expression and activity.
机译：肥胖相关病理的高发，导致了对参与脂肪细胞增殖和分化的机制的研究。在这里，我们证明了erbB2的调节在前脂肪细胞的增殖和成脂诱导中起着基本作用。使用3T3-L1细胞作为模型，我们证明EGF（10 nM，5分钟）除了刺激erbB2和EGFR的受体酪氨酸磷酸化外，还能够诱导异二聚体erbB2-EGFR。我们用两种抑制剂AG 825（IC（50）0.35 microM，对erbB2的选择性是对EGFR，IC（50）19 microM的54倍）和AG 879（IC（50）为1 microM的）抑制增殖的3T3-L1细胞对于erbB2来说是500 microM，对于EGFR是500 microM。我们发现，两者均以剂量依赖性方式抑制增殖，AG825在100 microM时达到30％的最大抑制率（P <0.001），AG 879在10 microM时达到20％的最大抑制率（P <0.001）。结果涉及erbB2在3T3-L1的增殖中。在研究分化过程时，我们发现MIX-Dexa的作用立即激活了MEK，JNK和p38激酶。我们观察到，在MIX-Dexa诱导之前1小时添加的PD98059和SP600125（分别为MEK-ERK和JNK抑制剂）在6 h后产生erbB2表达下降，甚至大于诱导剂MIX-德克萨这项工作支持erbB2作为3T3-L1脂肪形成的关键因素，不仅在增殖阶段而且在通过调节其表达和活性进行分化期间都发挥主要作用。

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