n-6 and n-3 polyunsaturated fatty acids down-regulate cytochrome P-450 2B1 gene expression induced by phenobarbital in primary rat hepatocytes

The Journal of Nutritional Biochemistry
Chien-Chun LiHaw-Wen Chen

Abstract

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] (SQ2...Continue Reading

Citations

Oct 1, 2008·International Journal of Obesity : Journal of the International Association for the Study of Obesity·D MullerovaM Matejovic
Oct 24, 2013·Nutrition Reviews·Dimitrios G BouzianasApostolos I Hatzitolios
Dec 3, 2014·Molecular and Cellular Endocrinology·B S DunbarR J Deckelbaum
Aug 12, 2009·Expert Opinion on Drug Metabolism & Toxicology·Jigar P Patel, Dion R Brocks
Jul 18, 2009·The American Journal of Pathology·Jingsheng TuoChi-Chao Chan
Feb 7, 2013·Pharmacological Reviews·Hywel D WilliamsChristopher J H Porter
Sep 10, 2008·The Biochemical Journal·Robert D FinnC Roland Wolf

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