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首页> 外文期刊>The Journal of Nutritional Biochemistry >n-6 and n-3 polyunsaturated fatty acids down-regulate cytochrome P-450 2B1 gene expression induced by phenobarbital in primary rat hepatocytes
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n-6 and n-3 polyunsaturated fatty acids down-regulate cytochrome P-450 2B1 gene expression induced by phenobarbital in primary rat hepatocytes

机译：n-6和n-3多不饱和脂肪酸下调苯巴比妥在原代大鼠肝细胞中诱导的细胞色素P-450 2B1基因表达

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摘要

In mammals, polyunsaturated fatty acids (PUFAs) act not only as an important energy source, but also as substrates for cellular membrane and hormone formation. They also play key roles in cellular metabolism and gene regulation. The objective of the present study was to determine whether individual n-6 and n-3 PUFAs affect cytochrome P-450 2B1 (CYP 2B1) expression induced by phenobarbital (PB) in primary rat hepatocytes. We used 100-microM arachidonic acid (AA), linoleic acid, eicosapentaenoic acid and docosahexaenoic acid (DHA) to test this hypothesis. Phenobarbital-induced CYP 2B1 expression was down-regulated by n-6 and n-3 PUFAs, especially AA and DHA. Prostaglandin (PG) E2 but not PGE3 was found to down-regulate PB-induced CYP 2B1 expression. The cyclooxygenase inhibitor indomethacin (20 microM) attenuated the down-regulation of CYP 2B1 gene expression by n-6 and n-3 PUFAs induced by PB, and maximal attenuation was found in the AA-treated group. We also studied the PGE2 downstream cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway to determine its role in the down-regulation of CYP 2B1 expression by AA with the use of 0.4 mM of the adenylate cyclase inhibitor 9-(tetrahydro-2'-furyl)adenine] (SQ22536) and 7.5 microM of the PKA inhibitor H-89. Both inhibitors attenuated the down-regulation of CYP 2B1 expression by AA. These results suggest that PB-induced CYP 2B1 expression is down-regulated by n-6 and n-3 PUFAs through different pathways. Prostaglandin E2 and the cAMP-dependent PKA pathway were involved in AA down-regulation of CYP 2B1 expression, whereas the down-regulation by n-3 PUFAs is not fully understood yet and the glucocorticoid receptor/constitutive androstane receptor/retinoid X receptor signal transduction cascade can be involved.
机译：在哺乳动物中，多不饱和脂肪酸（PUFA）不仅充当重要的能源，而且还充当细胞膜和激素形成的底物。它们在细胞代谢和基因调控中也起着关键作用。本研究的目的是确定单个n-6和n-3 PUFA是否影响苯巴比妥（PB）在原代大鼠肝细胞中诱导的细胞色素P-450 2B1（CYP 2B1）表达。我们使用100-microM花生四烯酸（AA），亚油酸，二十碳五烯酸和二十二碳六烯酸（DHA）来检验该假设。苯巴比妥诱导的CYP 2B1表达被n-6和n-3 PUFA特别是AA和DHA下调。发现前列腺素（PG）E2但不是PGE3下调PB诱导的CYP 2B1表达。环氧合酶抑制剂吲哚美辛（20 microM）通过PB诱导的n-6和n-3 PUFA减轻CYP 2B1基因表达的下调，在AA处理组中发现最大程度的衰减。我们还研究了PGE2下游环状单磷酸腺苷（cAMP）依赖性蛋白激酶A（PKA）通路，以确定其在通过使用0.4 mM腺苷酸环化酶抑制剂9-（AA）来下调CYP 2B1表达中的作用。四氢-2'-呋喃基腺嘌呤]（SQ22536）和7.5 microM的PKA抑制剂H-89。两种抑制剂均减弱了AA对CYP 2B1表达的下调。这些结果表明，n-6和n-3 PUFA通过不同途径下调了PB诱导的CYP 2B1表达。前列腺素E2和cAMP依赖性PKA通路参与了AA下调CYP 2B1的表达，而对n-3 PUFA的下调尚不完全了解，糖皮质激素受体/组成型雄烷受体/类维生素X受体信号转导级联可以参与。

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