Dietary n-6 PUFA deprivation downregulates arachidonate but upregulates docosahexaenoate metabolizing enzymes in rat brain.

Dietary n-6 PUFA deprivation downregulates arachidonate but upregulates docosahexaenoate metabolizing enzymes in rat brain.
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DOI:
10.1016/j.bbalip.2010.10.005
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发表时间:
2011-02
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Igarashi M
Igarashi M
中科院分区:
其他
文献类型:
--
作者:
Kim HW;Rao JS;Rapoport SI;Igarashi M

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饮食n-3多不饱和脂肪酸(PUFA)剥夺增加了大鼠脑中花生四烯酸(AA 20:4 n-6)选择性胞浆磷脂酶A2(cPLA 2)IVA和环氧合酶(考克斯)-2的表达,同时降低了二十二碳六烯酸(DHA 22:6 n-3)选择性钙非依赖性iPLA 2 VIA的表达。假设这些酶的变化代表了大脑对剥夺的稳态反应,我们假设饮食n-6 PUFA剥夺会产生相反方向的变化。在断奶后15周喂食n-6 PUFA充足或不足饮食的雄性大鼠中,定量PUFA代谢酶及其转录因子的脑表达。与适饲组相比,缺饲组大鼠脑组织中iPLA 2 VIA和15-脂氧合酶(LOX)的mRNA、蛋白质和活性增加,cPLA 2 IVA和考克斯-2的表达降低。iPLA 2转录因子SREBP-1的脑蛋白水平升高,而AP-2α和NF-κB p65、cPLA 2和考克斯-2转录因子的蛋白水平分别降低。随着饮食n-6 PUFA剥夺,大鼠脑PUFA代谢酶和它们的一些转录因子以一种方式改变,这种方式将稳态地抑制脑n-6 PUFA浓度和代谢的降低,而n-3 PUFA代谢酶的表达增加。这些变化对应于报道的AA与DHA相比的体外酶选择性。(198字)
Dietary n-3 polyunsaturated fatty acid (PUFA) deprivation increases expression of arachidonic acid (AA 20:4n-6)-selective cytosolic phospholipase A2 (cPLA2) IVA and cyclooxygenase (COX)-2 in rat brain, while decreasing expression of docosahexaenoic acid (DHA 22:6n-3)-selective calcium-independent iPLA2 VIA. Assuming that these enzyme changes represented brain homeostatic responses to deprivation, we hypothesized that dietary n-6 PUFA deprivation would produce changes in the opposite directions. Brain expression of PUFA-metabolizing enzymes and their transcription factors was quantified in male rats fed an n-6 PUFA adequate or deficient diet for 15 weeks post-weaning. The deficient compared with adequate diet increased brain mRNA, protein and activity of iPLA2 VIA and 15-lipoxygenase (LOX), but decreased cPLA2 IVA and COX-2 expression. The brain protein level of the iPLA2 transcription factor SREBP-1 was elevated, while protein levels were decreased for AP-2α and NF-κB p65, cPLA2 and COX-2 transcription factors, respectively. With dietary n-6 PUFA deprivation, rat brain PUFA metabolizing enzymes and some of their transcription factors change in a way that would homeostatically dampen reductions in brain n-6 PUFA concentrations and metabolism, while n-3 PUFA metabolizing enzyme expression is increased. The changes correspond to reported in vitro enzyme selectivities for AA compared with DHA. (198 words)
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