Glucocorticoids induce proteasome C3 subunit expression in L6 muscle cells by opposing the suppression of its transcription by NF-κB
Glucocorticoids induce proteasome C3 subunit expression in L6 muscle cells by opposing the suppression of its transcription by NF-κB
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DOI：
10.1074/jbc.m907258199
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发表时间：
2000-06-30
影响因子：
4.8
通讯作者：
Price, SR
中科院分区：
文献类型：
--
作者：
Du, J;Mitch, WE;Price, SR
分解代谢条件下的肌肉萎缩是由于泛素-蛋白酶体蛋白水解途径的激活所致，该过程需要糖皮质激素，并且通常与编码该蛋白水解系统成分的 mRNA 水平增加有关。在 L6 肌细胞中，地塞米松刺激蛋白水解，并通过增强转录来增加蛋白酶体 C3 亚基蛋白的数量。人 C3 启动子-荧光素酶报告基因转染研究和电泳迁移率变动分析表明，L6 肌细胞核中富含含有 Rel A 的 NF-kappa B 蛋白复合物，糖皮质激素通过拮抗该 NF-kappa B 蛋白与 C3 亚基启动子区域中 NF-kappa B 反应元件的相互作用来刺激 C3 亚基表达。地塞米松还增加了 L6 细胞中 NF-kappa B p65 亚基和 I kappa B α 抑制剂蛋白的胞质含量。将 L6 细胞与细胞因子混合物一起孵育不仅增加了活化 NF-κ B 的量，而且还降低了 C3 启动子活性并降低了内源性 C3 亚基 mRNA。因此，NP-kappa B 是肌肉细胞中 C3 蛋白酶体亚基转录的抑制因子，糖皮质激素通过对抗这种抑制作用来刺激 C3 亚基表达。
Muscle wasting in catabolic conditions results from activation of the ubiquitin-proteasome proteolytic pathway by a process that requires glucocorticoids and is generally associated with increased levels of mRNAs encoding components of this proteolytic system. In L6 muscle cells, dexamethasone stimulates proteolysis and increases the amount of the proteasome C3 subunit protein by augmenting its transcription. Transfection studies with human C3 promoter-luciferase reporter genes and electrophoretic mobility shift assays revealed that a NF-kappa B-protein complex containing Rel A is abundant in L6 muscle cell nuclei, Glucocorticoids stimulate C3 subunit expression by antagonizing the interaction of this NF-kappa B protein with an NF-kappa B response element in the C3 subunit promoter region. Dexamethasone also increased the cytosolic amounts of the NF-kappa B p65 subunit and the I kappa B alpha inhibitor proteins in L6 cells. Incubation of L6 cells with a cytokine mixture not only increased the amount of activated NF-kappa B but also decreased C3 promoter activity and lowered endogenous C3 subunit mRNA. Thus, NP-kappa B is a repressor of C3 proteasome subunit transcription in muscle cells, and glucocorticoids stimulate C3 subunit expression by opposing this suppressor action.