High stearoyl-CoA desaturase protein and activity levels in simian virus 40 transformed-human lung fibroblasts
High stearoyl-CoA desaturase protein and activity levels in simian virus 40 transformed-human lung fibroblasts
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DOI：
10.1016/j.bbalip.2004.11.015
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发表时间：
2005-02-21
影响因子：
4.8
通讯作者：
Igal, RA
中科院分区：
文献类型：
--
作者：
Scaglia, N;Caviglia, JM;Igal, RA
单不饱和脂肪酸（MUFA）合成在细胞增殖和程序性细胞死亡中的确切作用尚不清楚。高水平的MUFA与肿瘤表型的强相关性表明，硬脂酰辅酶a去饱和酶（SCD）的调节在癌症发展中必须发挥重要作用。本研究研究了正常（W138）和sv40转化（SV40-W138）人肺成纤维细胞中SCD蛋白水平和活性。因此，与W138成纤维细胞相比，SV40-WI38中SCD对外源性[C-14]硬脂酸和内源性[C-14]乙酸标记脂肪酸的活性分别增加了2.2倍和2.6倍。同时，在sv40转化的细胞中，SCD蛋白含量增加了3.3倍。细胞转化也导致高水平的MUFA，这与更流体的膜环境是平行的。此外，ppar - γ（一种众所周知的SCD表达激活剂）的水平在sv40转化的成纤维细胞中高度升高。SCD活性似乎与程序性细胞死亡事件有关，因为用40 muM etoposide孵育可诱导SV40细胞凋亡，并导致脂肪酸合成、SCD活性和MUFA细胞水平降低。综上所述，这些结果表明SCD蛋白和活性水平与肿瘤细胞转化和程序性细胞死亡事件有关。(C) 2004 Elsevier B.V.版权所有
The precise role of monounsaturated fatty acid (MUFA) synthesis in cell proliferation and programmed cell death remains unknown. The strong correlation of high levels of MUFA and neoplastic phenotype suggest that the regulation of stearoyl CoA desaturase (SCD) must play a significant role in cancer development. In this study, the levels of SCD protein and activity were investigated in normal (W138) and SV40-transformed (SV40-W138) human lung fibroblasts. Thus, the activity of SCD on exogenous [C-14] stearic acid and endogenous [C-14]acetate-labeled fatty acids was increased by 2.2- and 2.6-fold, respectively, in SV40-WI38 compared to W138 fibroblasts. Concomitantly, a 3.3-fold increase in SCD protein content was observed in SV40-transformed cells. Cell transformation also led to high levels of MUFA, which was paralleled by a more fluid membrane environment. Furthermore, the levels of PPAR-gamma, a well-known activator of SCD expression, were highly increased in SV40-transformed fibroblasts. SCD activity appeared linked to the events of programmed cell death, since incubations with 40 muM etoposide induced apoptosis in SV40 cells, and led to a decrease in fatty acid synthesis, SCD activity and in MUFA cellular levels. Taken together, these results suggest that SCD protein and activity levels are associated with the events of neoplastic cell transformation and programmed cell death. (C) 2004 Elsevier B.V. All rights reserved.