Dihydrocapsaicin down-regulates apoM expression through inhibiting Foxa2 expression and enhancing LXRα expression in HepG2 cells.

Abstract

BACKGROUND:

Apolipoprotein M (apoM), as a novel apolipoprotein which is mainly expressed in liver and kidney tissues, is associated with development and progression of atherosclerosis and diabetes. Our group have recently shown that Dihydrocapsaicin(DHC)can significantly decrease atherosclerotic plaque formation in apoE-/- mice. However, the effect and possible mechanism of DHC on apoM expression remain unclear.

METHODS:

HepG2 cells were treated with 0 μM, 25 μM, 50 μM and 100 μM DHC for 24 h or were treated with 100 μM DHC for 0, 6, 12, and 24 h, respectively. The mRNA levels and protein levels were measured by real-time quantitative PCR and western blot analysis, respectively.

RESULTS:

We found that DHC markedly decreased expression of apoM at both mRNA and protein level in HepG2 cells in a dose-dependent and time-dependent manner. Expression of Foxa2 was decreased while expression of LXRα was increased by DHC treatment in HepG2 cells. In addittion, overexpression of Foxa2 markedly compensated the inhibition effect induced by DHC on apoM expression. LXRα small interfering RNA significantly abolished the inhibition effect which induced by DHC on apoM expression. The liver of C57BL/6 mice treated with DHC had significantly lower expression of apoM. Furthermore, the liver had lower expression of Foxa2 while had higher expression of LXRα.

CONCLUSIONS:

DHC could down-regulate apoM expression through inhibiting Foxa2 expression and enhancing LXRα expression in HepG2 cells.

• Authors: Jia-Yi Zhao, Yan-Wei Hu, Shu-Fen Li, Ya-Rong Hu, Xin Ma, Shao-Guo Wu, Yan-Chao Wang, Ji-Juan Gao, Yan-Hua Sha, Lei Zheng, Qian Wang
• Journal: Lipids in health and disease (Lipids Health Dis) Vol. 13 Pg. 50 (Mar 19 2014) ISSN: 1476-511X [Electronic] England
• PMID: 24642298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• APOM protein, human
• Apolipoproteins
• Apolipoproteins M
• FOXA2 protein, human
• Lipocalins
• Liver X Receptors
• NR1H3 protein, human
• Nr1h3 protein, mouse
• Orphan Nuclear Receptors
• Hepatocyte Nuclear Factor 3-beta
• Capsaicin
• dihydrocapsaicin

Topics

• Apolipoproteins (metabolism)
• Apolipoproteins M
• Capsaicin (analogs & derivatives, pharmacology)
• Gene Expression (drug effects)
• Hep G2 Cells
• Hepatocyte Nuclear Factor 3-beta (metabolism)
• Humans
• Lipocalins (metabolism)
• Liver X Receptors
• Orphan Nuclear Receptors (metabolism)