Berberine-induced LDLR up-regulation involves JNK pathway.
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.
Lee
Seahyoung
S
Yonsei Cardiovascular Genome Center, College of Medicine, Yonsei University, Seoul, Republic of Korea.
Lim
Hyun-Joung
HJ
Park
Jin-Hee
JH
Lee
Kuy-Sook
KS
Jang
Yangsoo
Y
Park
Hyun-Young
HY
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
D000873:Anthracenes; D011973:Receptors, LDL; D001599:Berberine; C432165:pyrazolanthrone; D048670:MAP Kinase Kinase 4