Independent arachidonic acid-mediated gene regulatory pathways in lymphocytes.

Independent arachidonic acid-mediated gene regulatory pathways in lymphocytes.
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淋巴细胞中独立的花生四烯酸介导的基因调控途径。

DOI:
10.1006/bbrc.1993.1901
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发表时间:
1993
影响因子:
3.1
通讯作者:
T. Buttke
T. Buttke
中科院分区:
生物学4区
文献类型:
--
作者:
P. Tebbey;T. Buttke

文献摘要

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在BW 5147 T细胞系中,我们已经确定了两个独立的调节途径,花生四烯酸(20:4)可以改变基因表达。20:4对硬脂酰辅酶A去饱和酶2(SCD 2)基因表达的抑制作用被认为是独立的氧化20:4的脂氧合酶或环氧合酶途径。此外,20:4的氧化代谢产物(15-HPETE和15-HETE)未能减少SCD 2 mRNA的积累,而20:4本身在完全抑制SCD 2基因表达方面是有效的。与此相反,原癌基因c-fos的转录诱导依赖于20:4通过脂氧合酶途径的氧化。通过使用蛋白质合成抑制剂,放线菌酮,我们还表明,20:4介导的调节作用,对SCD 2或c-fos是完全独立的新的蛋白质合成。总的来说,结果确定存在多个,独立的,细胞内20:4-介导的调节途径,同时在这种细胞类型。
In the BW5147 T cell line, we have identified two independent regulatory pathways by which arachidonic acid (20:4) can alter gene expression. The inhibitory effect of 20:4 upon stearoyl-CoA desaturase 2 (SCD2) gene expression was seen to be independent of oxidation of 20:4 by either the lipoxygenase or cyclooxygenase pathways. Moreover, oxidized metabolites of 20:4 (15-HPETE and 15-HETE) failed to diminish SCD2 mRNA accumulation whereas 20:4 itself was effective in completely suppressing SCD2 gene expression. In contrast, the transcriptional induction of the proto-oncogene c-fos was dependent upon the oxidation of 20:4 by the lipoxygenase pathway. By using the protein synthesis inhibitor, cycloheximide, we also show that the 20:4-mediated regulatory effects upon SCD2 or c-fos are completely independent of new protein synthesis. Collectively, the results identify the existence of multiple, independent, intracellular 20:4-mediated regulatory pathways operating simultaneously within this cell type.