title: Berberine-induced LDLR up-regulation involves JNK pathway.
abstract: Berberine, an herbal alkaloid, has been reported to have a lipid lowering effect by stabilizing hepatic LDLR mRNA in an ERK-dependent manner rather than promoting transcriptional activity. However, considering the complexity of interconnected signal pathways in biological processes, it is highly possible that there exist signal pathway(s) other than ERK pathway which contribute to the berberine-induced up-regulation of LDLR. In the present study, we examined possible involvement of other signal pathways in berberine-induced hepatic LDLR up-regulation. As evidenced by RT-PCR, berberine-induced LDLR mRNA expression was inhibited by JNK inhibitor SP600125 pretreatment. Furthermore, we demonstrate that putative c-jun binding site of LDLR promoter is important in berberine-induced LDLR transcription using luciferase assay. The result of EMSA also shows that berberine induces c-jun binding to LDLR promoter and this is decreased by SP600125 pretreatment. The present study demonstrates that berberine increases transcriptional activity of LDLR promoter and this involves JNK pathway.
authors.affiliation: Yonsei Cardiovascular Genome Center, College of Medicine, Yonsei University, Seoul, Republic of Korea.
authors.forename: Seahyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Hyun-Joung
authors.initials: HJ
authors.lastname: Lim
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Kuy-Sook
authors.initials: KS
authors.lastname: Lee
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Park
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D001599:Berberine / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000187:drug effects*; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000873:Anthracenes; D011973:Receptors, LDL; D001599:Berberine; C432165:pyrazolanthrone; D048670:MAP Kinase Kinase 4