Mitogen-activated protein kinase activation is not necessary for, but antagonizes, 3T3-L1 adipocytic differentiation
Mitogen-activated protein kinase activation is not necessary for, but antagonizes, 3T3-L1 adipocytic differentiation
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DOI：
10.1128/mcb.17.10.6068
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发表时间：
1997-10-01
影响因子：
5.3
通讯作者：
Santos, E
中科院分区：
文献类型：
--
作者：
deMora, JF;Porras, A;Santos, E
在3 T3-L1成纤维细胞中，Ras蛋白介导胰岛素诱导的向脂肪细胞的分化及其对胞质丝氨酸/苏氨酸激酶（包括Raf-1激酶、促分裂原活化蛋白激酶（MAPK）和Rsk）的活化。在这里，我们报告说，胰岛素和Ras诱导的MAPK激活是不需要的分化过程中，实际上拮抗它，治疗3 T3-L1前脂肪细胞与MEK特异性抑制剂PD 98059阻断胰岛素和Ras诱导的MAPK激活，但没有影响或略有增强脂肪细胞分化。肿瘤坏死因子α（TNF-α）是胰岛素刺激的脂肪生成的抑制剂，其激活3 T3-L1细胞中的MAPK。PD 98059处理阻断了TNF-α对MAPK的激活，并逆转了低浓度（1 ng/ml）TNF-α对脂肪生成介导的阻断。含有过度活化的MEK 1或过表达的MAPK的3 T3-L1转染子显示出受损的脂肪细胞分化，PD 98059处理还逆转了MEK 1转染子中的分化阻断。这些结果表明，MAPK不促进，但可以有助于抑制3 T3-L1细胞的脂肪细胞分化的过程。
In 3T3-L1 fibroblasts, Ras proteins mediate both insulin-induced differentiation to adipocytes and its activation of cytosolic serine/threonine kinases, including Raf-1 kinase, mitogen-activated protein kinase (MAPK), and Rsk. Here, we report that insulin-and Ras-induced activation of MAPK is not required for the differentiation process and in fact antagonizes it, The treatment of 3T3-L1 preadipocytes with MEK-specific inhibitor PD98059 blocked insulin- and Ras-induced MAPK activation but had no effect on or slightly enhanced adipocytic differentiation. Tumor necrosis factor alpha (TNF-alpha), an inhibitor of insulin stimulated adipogenesis, activated MAPK in 3T3-L1 cells. PD98059 treatment blocked MAPK activation by TNF-alpha and reversed the blockade of adipogenesis mediated bg low (1 ng/ml) TNF-alpha concentrations. 3T3-L1 transfectants containing hyperactivated MEK1 or overexpressed MAPK displayed impaired adipocytic differentiation, PD98059 treatment also reversed the blockade of differentiation in MEK1 transfectants. These results indicate that MAPK does not promote but can contribute to inhibition of the process of adipocytic differentiation of 3T3-L1 cells.