Berberine decreases PCSK9 expression in HepG2 cells.
BACKGROUND
Proprotein convertase subtilisin/kexin type 9 (PCSK9) post-transcriptionally downregulates the low-density lipoprotein receptor (LDLR) by binding to the receptor's epidermal growth factor repeat A on the cell surface and shuttling the LDLR to the lysosomes for degradation. Mutations in the PCSK9 gene have been shown to cause either hypo- or hypercholesterolemia. Here we investigated the effect of berberine, a natural plant extract, on PCSK9 expression in HepG2 cells.


RESULTS
Berberine decreases PCSK9 mRNA and protein levels in a time- and dose-dependent manner. This was not due to increased degradation of PCSK9 mRNA but most likely due to a decreased transcription of the PCSK9 gene. We also show that a combination of berberine and mevastatin increases LDLR mRNA and protein levels, while suppressing the increase in PCSK9 mRNA levels caused by mevastatin alone.


CONCLUSIONS
Berberine may be a useful supplement to statin treatment due to its effects on PCSK9 mRNA and protein levels.
Cameron
Jamie
J
Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet University Hospital, Oslo, Norway. jamie.cameron@rikshospitalet.no
Ranheim
Trine
T
Kulseth
Mari Ann
MA
Leren
Trond P
TP
Berge
Knut Erik
KE
D000924:Anticholesteremic Agents / Q000494:pharmacology; D001599:Berberine / Q000494:pharmacology*; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology; D010936:Plant Extracts / Q000378:metabolism; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D013997:Time Factors; D014158:Transcription, Genetic
D000924:Anticholesteremic Agents; D010936:Plant Extracts; D012333:RNA, Messenger; D011973:Receptors, LDL; D001599:Berberine; D003609:Dactinomycin; C012258:mevastatin; D008148:Lovastatin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases