{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T20:13:34Z","timestamp":1760645614227},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,9,19]],"date-time":"2008-09-19T00:00:00Z","timestamp":1221782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NSC","award":["95-2320-B-040-029-MY2"],"award-info":[{"award-number":["95-2320-B-040-029-MY2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mitogen\u2010activated protein kinase (MAPK) pathways play central roles in the transduction of extracellular stimuli into cells and the regulation of expression of numerous genes. Docosahexaenoic acid (DHA) was shown to be involved in the regulation of expression of drug metabolizing enzymes (DMEs) in rat primary hepatocytes in response to xenobiotics. Cytochrome P450 2B1 (CYP 2B1) is a DME that is dramatically induced by phenobarbital\u2010type inducers. The constitutive androstane receptor (CAR) plays a critical role in regulating the expression of DMEs, and the phosphorylation\/dephosphorylation of CAR is an important event in CYP 2B1 expression. In the present study, we determined the effect of DHA on MAPK transactivation and its role in CYP 2B1 expression induced by phenobarbital. c\u2010Jun NH2\u2010terminal kinase (JNK) JNK1\/2 and ERK1\/2 were activated by phenobarbital in a dose\u2010dependent manner. DHA (100 \u03bcM) inhibited JNK1\/2 and ERK2 activation induced by phenobarbital in a time\u2010dependent manner. Both SP600125 (a JNK inhibitor) and SB203580 (a p38 MAPK inhibitor) inhibited CYP 2B1 protein and mRNA expression induced by phenobarbital. SB203580 significantly increased the intracellular 3\u2032\u20105\u2032\u2010cyclic adenosine monophosphate (cAMP) concentration compared with a control group (<jats:italic>p<\/jats:italic> &lt; 0.05). Our results suggest that inhibition of JNK activation by DHA is at least part of the mechanisms of DHA's downregulation of CYP 2B1 expression induced by phenobarbital.<\/jats:p>","DOI":"10.1002\/mnfr.200800112","type":"journal-article","created":{"date-parts":[[2008,9,19]],"date-time":"2008-09-19T15:28:09Z","timestamp":1221838089000},"page":"341-348","source":"Crossref","is-referenced-by-count":7,"title":["Docosahexaenoic acid downregulates phenobarbital\u2010induced cytochrome P450 2B1 gene expression in rat primary hepatocytes <i>via <\/i>the c\u2010Jun NH2\u2010terminal kinase mitogen\u2010activated protein kinase pathway"],"prefix":"10.1002","volume":"53","author":[{"given":"Chia\u2010Yang","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien\u2010Chun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai\u2010Li","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong\u2010Kuei","family":"Lii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haw\u2010Wen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,3,3]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)34276-0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1207\/s15327914nc5202_12"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-005-2415-z"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2006.04.003"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02859265"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665107005411"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-004-0087-5"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2002.10719248"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.09.005"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-007-0518-y"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1207\/s15327914nc5001_10"},{"key":"e_1_2_1_13_2","first-page":"785","article-title":"A combination of docosahexaenoic acid and celecoxib prevents prostate cancer cell growth in vitro and is associated with modulation of nuclear factor\u2010kappaB, and steroid hormone receptors","volume":"26","author":"Narayanan N.\u2010K.","year":"2005","journal-title":"Int. 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