Inhibition of microsomal triglyceride transfer protein expression and atherogenic risk factor apolipoprotein B100 secretion by tanshinone IIA in HepG2 cells.
Salvia miltiorrhiza Bunge is known to be effective for the treatment of cardiovascular diseases. Here, we have isolated tanshinone IIA (T-IIA) from S. miltiorrhiza Bunge. The aim of this study is to address the mechanisms where apolipoprotein B-100 (ApoB) regulation is associated with T-IIA, since T-IIA regulates the lipoprotein metabolism in liver cells. Human HepG2 cells treated with T-IIA for 24 h exerted a dose-dependent inhibitory effect on ApoB secretion together with triglyceride. However, another secretory protein, albumin, was unaffected by T-IIA treatment, indicating that the effect of T-IIA is specific for ApoB secretion. T-IIA decreased the transcription level of microsomal triglyceride transfer protein gene, suggesting that lipoprotein assembly is likely to be involved in the inhibited ApoB secretion. Interestingly, T-IIA inhibited ApoB secretion via a proteasome-dependent pathway. Our results suggest that T-IIA is an influential inhibitor of ApoB secretion and triglyceride secretion in liver cells.
Kang
Yun-Jeong
YJ
Department of Biological Science, Sungkyunkwan University, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea.
Jin
Un-Ho
UH
Chang
Hyen-Wook
HW
Son
Jong-Keun
JK
Lee
Seung Ho
SH
Son
Kun-Ho
KH
Chang
Young-Chae
YC
Lee
Young-Choon
YC
Kim
Cheorl-Ho
CH
D045784:Abietanes; D000418:Albumins / Q000378:metabolism; D053299:Apolipoprotein B-100 / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D010616:Phenanthrenes / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D013379:Substrate Specificity; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism
D045784:Abietanes; D000418:Albumins; D053299:Apolipoprotein B-100; D002352:Carrier Proteins; D010616:Phenanthrenes; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; C021751:tanshinone; D046988:Proteasome Endopeptidase Complex