MCP-1 induced protein promotes adipogenesis via oxidative stress, endoplasmic reticulum stress and autophagy.
MCP-1 induced protein promotes adipogenesis via oxidative stress, endoplasmic reticulum stress and autophagy.
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MCP-1 诱导蛋白通过氧化应激、内质网应激和自噬促进脂肪生成。
DOI：
10.1159/000339066
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Kolattukudy,Pappachan
中科院分区：
文献类型：
--
作者：
Younce,Craig;Kolattukudy,Pappachan
肥胖与炎症有关。已知MCP-1（一种炎性趋化因子）和MCP-1诱导蛋白（MCPIP）诱导脂肪形成，导致脂肪细胞数量增加。在这里，我们阐明的中间过程，通过MCPIP诱导脂肪形成。在3T3-L1前脂肪细胞中强制表达MCPIP导致活性氧/氮物质（ROS/RNS）产生和诱导型一氧化氮合酶（iNOS）表达增加，内质网应激（ER），如ER伴侣蛋白和蛋白质二硫键异构酶表达所示，以及自噬，如beclin-1表达和LC 3裂解所示。ROS抑制剂夹竹桃苷的处理减弱了MCPIP对脂肪形成的诱导，如通过诱导参与脂肪形成的转录因子、脂肪细胞标志物和脂滴积累所测量的。用牛磺熊去氧胆酸盐或敲低肌醇需要酶1（IRE1）抑制ER应激可抑制MCPIP诱导的自噬和脂肪生成。前脂肪细胞在诱导脂肪形成的鸡尾酒表现出ER应激和自噬。敲除MCPIP减弱了这些作用。MCPIP诱导p38活化，p38抑制剂SB 203580减弱MCPIP诱导的脂肪生成。
Obesity involves inflammation. MCP-1, an inflammatory chemokine, and MCP-1-induced protein (MCPIP) are known to induce adipogenesis that causes increase in the number of adipocytes. Here we elucidate the intermediate processes through which MCPIP induces adipogenesis. Forced expression of MCPIP in 3T3-L1 preadipocytes caused increased reactive oxygen/nitrogen species (ROS/RNS) production and inducible-nitric oxide synthase (iNOS) expression, endoplasmic reticulum stress (ER), as indicated by expression of ER chaperones and protein disulfide isomerase, and autophagy as indicated by expression of beclin-1 and cleavage of LC3. Treatment of ROS inhibitor, apocynin attenuated MCPIP induction of adipogenesis as measured by the induction of transcription factors involved in adipogenesis, adipocyte markers and lipid droplet accumulation. Inhibition of ER stress with taurursodeoxycholate or knockdown of inositol requiring enzyme 1 (IRE1) inhibited MCPIP induced autophagy and adipogenesis. Preadipocytes in adipogenesis-inducing cocktail manifested ER stress and autophagy. Knockdown of MCPIP attenuated these effects. MCPIP induced p38 activation and p38 inhibitor, SB203580, attenuated MCPIP-induced adipogenesis.