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磷脂酶D作为多不饱和脂肪酸对大鼠胸腺细胞抗增殖作用的潜在靶点。

Phospholipase D as a potential target for the antiproliferative effects of polyunsaturated fatty acids in rat thymocytes.

作者信息

Benzaria Amal, Meskini Nadia, Dubois Madeleine, Némoz Georges, Lagarde Michel, Prigent Annie-France

机构信息

ALNSERM U585, INSA-Lyon, Physiopathologie des Lipides et Membranes, IMBL, F-69621 Villeurbanne, France.

出版信息

J Nutr Biochem. 2007 Apr;18(4):228-35. doi: 10.1016/j.jnutbio.2006.03.009. Epub 2006 May 18.

DOI:10.1016/j.jnutbio.2006.03.009
PMID:16713231
Abstract

The effects of various saturated and unsaturated fatty acids (FAs) on the proliferative response and phospholipase D (PLD) activity of rat thymocytes were investigated. When added to culture medium as complexes with albumin, all the FAs tested, except stearic acid, inhibited the ConA-induced thymocyte proliferation, eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids being the most inhibitory. Apart from 22:6n-3 which slightly increased the percentage of late apoptotic and necrotic thymocytes in the presence of mitogen, none of the FAs induced significant apoptosis or necrosis. A short 2-h preincubation of rat thymocytes in the presence of FA-albumin complexes was sufficient to induce a significant enrichment of cell phospholipids with each FA and to stimulate thymocyte PLD activity. However, 20:5n-3 was inactive despite a large enrichment in phospholipids. Furthermore, the PLD activity of activated thymocytes was negatively correlated to the proliferative response, with the exception of 20:5n-3-supplemented cells. These results support further our current hypothesis that PLD activity conveys antiproliferative signals in lymphoid cells, and suggest that 20:5n-3 inhibits thymocyte proliferation by a particular mechanism unrelated to that of the other FAs.

摘要

研究了各种饱和脂肪酸和不饱和脂肪酸(FAs)对大鼠胸腺细胞增殖反应和磷脂酶D(PLD)活性的影响。当与白蛋白形成复合物添加到培养基中时,除硬脂酸外,所有测试的脂肪酸均抑制刀豆蛋白A诱导的胸腺细胞增殖,其中二十碳五烯酸(20:5n-3)和二十二碳六烯酸(22:6n-3)的抑制作用最强。除22:6n-3在有丝分裂原存在时略微增加晚期凋亡和坏死胸腺细胞的百分比外,没有一种脂肪酸能诱导显著的凋亡或坏死。在FA-白蛋白复合物存在下对大鼠胸腺细胞进行2小时的短暂预孵育,足以使每种脂肪酸显著富集细胞磷脂并刺激胸腺细胞PLD活性。然而,尽管磷脂大量富集,20:5n-3仍无活性。此外,活化胸腺细胞的PLD活性与增殖反应呈负相关,但添加20:5n-3的细胞除外。这些结果进一步支持了我们目前的假设,即PLD活性在淋巴细胞中传递抗增殖信号,并表明20:5n-3通过一种与其他脂肪酸不同的特殊机制抑制胸腺细胞增殖。

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