Ye H, Serrero G
Neurosciences Department, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Biochem J. 1998 Mar 1;330 ( Pt 2)(Pt 2):803-9. doi: 10.1042/bj3300803.
Adipose differentiation related protein (ADRP) is a 50 kDa protein expressed at high level in differentiated adipocytes. ADRP expression is very low in undifferentiated adipocytes and increases rapidly and dramatically as the cells undergo adipose differentiation. In the present study, we demonstrate that ADRP expression at the mRNA and protein level is stimulated in adipocyte precursor cells in a time- and dose-dependent fashion by treatment with cyclooxygenase inhibitors, particularly indomethacin and ibuprofen. Lipoxygenase inhibitors such as AA861 and nordihydroguaiaretic acid were ineffective. Stimulation of ADRP expression was observed with 10(-5) M ibuprofen but maximal stimulation required a concentration of 3 x 10(-4) M. Nuclear run-on experiments indicated that indomethacin or ibuprofen stimulated the transcription of the ADRP gene in undifferentiated adipocytes. In addition to stimulating the induction of ADRP in undifferentiated cells, ibuprofen and indomethacin also stimulated the level of ADRP mRNA and protein in differentiated adipocytes. These experiments provide new information on the regulation of ADRP, an early inducible gene in the adipocyte differentiation programme in adipocyte precursors and in adipocytes and identify a new target for cyclooxygenase inhibitor action during adipocyte differentiation.
脂肪分化相关蛋白（ADRP）是一种50 kDa的蛋白，在分化的脂肪细胞中高水平表达。ADRP在未分化的脂肪细胞中表达非常低，并且随着细胞经历脂肪分化而迅速且显著增加。在本研究中，我们证明，用环氧化酶抑制剂，特别是吲哚美辛和布洛芬处理，可在脂肪细胞前体细胞中以时间和剂量依赖的方式刺激ADRP在mRNA和蛋白水平的表达。脂氧合酶抑制剂如AA861和去甲二氢愈创木酸无效。用10(-5) M布洛芬可观察到ADRP表达的刺激，但最大刺激需要3×10(-4) M的浓度。细胞核转录实验表明，吲哚美辛或布洛芬刺激未分化脂肪细胞中ADRP基因的转录。除了刺激未分化细胞中ADRP的诱导外，布洛芬和吲哚美辛还刺激分化脂肪细胞中ADRP mRNA和蛋白的水平。这些实验提供了关于ADRP调节的新信息，ADRP是脂肪细胞前体和脂肪细胞中脂肪细胞分化程序中的一个早期可诱导基因，并确定了环氧化酶抑制剂在脂肪细胞分化过程中的一个新作用靶点。
