scholarly journals Phytosterol-mediated inhibition of intestinal cholesterol absorption is independent of ATP-binding cassette transporter A1

2006 ◽  
Vol 95 (3) ◽  
pp. 618-622 ◽  
Author(s):  
Laura Calpe-Berdiel ◽  
Joan Carles Escolà-Gil ◽  
Francisco Blanco-Vaca

An increased activity of ATP-binding cassette transporter (ABC) A1 has been proposed as a mechanism underlying the hypocholesterolaemic effect of phytosterols. In the present study, ABCA1-deficient mice (ABCA1−/− mice) were used to examine the involvement of the ABCA1 in the reduction of intestinal cholesterol absorption in response to a phytosterol-enriched diet. A decrease in intestinal cholesterol absorption of 39 and 35% was observed after phytosterol treatment in ABCA1+/+ mice and in ABCA1−/− mice, respectively. No statistically significant changes in plasma lipoprotein profile or in intestinal ABCG5, ABCG8 and Niemann-Pick C1-Like 1 gene expression levels were found when phytosterol-treated ABCA1−/− mice and untreated ABCA1−/− mice were compared. We conclude that phytosterol inhibition of cholesterol absorption in mice is independent of ABCA1

2015 ◽  
Vol 18 (5) ◽  
pp. 765 ◽  
Author(s):  
Atsushi Kawase ◽  
Seiji Hata ◽  
Mai Takagi ◽  
Masahiro Iwaki

Purpose. Niemann-Pick C1-like 1 (NPC1L1), ATP-binding cassette (ABC)G5, and ABCG8 mediate intestinal cholesterol absorption. It is unclear whether pravastatin (PR) or ezetimibe (EZ) affect expression of these transporters. We examined the effects of PR and EZ on NPC1L1, ABCG5, and ABCG8 expression in human hepatoma HepG2 cells and the murine small intestine. We also assessed expression of the transcription factors liver X receptor (LXR)a, LXRb and sterol regulatory element-binding protein. Methods. Transporter mRNA levels were determined in murine small intestines 6 and 24 h after oral PR and EZ administration by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). In PR- and EZ-treated HepG2 cells, transporter and transcription factor mRNA and protein levels were examined by RT-PCR and western blot, respectively. Results. Significant decreases in NPC1L1, ABCG5, and ABCG8 mRNA expression were observed in the duodenum, but not jejunum and ileum, of mice 24 h after treatment with PR, but not EZ. In HepG2 cells, PR but not EZ treatment for 24 h also significantly decreased NPC1L1 protein and ABCG5, and ABCG8 mRNA expression, while increasing LXRa  mRNA levels. Conclusion. PR but not EZ treatment reduced duodenal cholesterol transporter expression in mice. PR-induced increases in LXRa  mRNA levels may be involved in attenuation of NPC1L1 expression, subsequently decreasing intestinal cholesterol absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


2008 ◽  
Vol 51 (5) ◽  
pp. 467-475 ◽  
Author(s):  
Xiao-yan Dai ◽  
Xiang Ou ◽  
Xin-rui Hao ◽  
Dong-li Cao ◽  
Ya-ling Tang ◽  
...  

2016 ◽  
Vol 36 (2) ◽  
Author(s):  
Hongyun Li ◽  
Tim Karl ◽  
Brett Garner

ATP-binding cassette transporter A7 (ABCA7) is expressed in the brain and linked with Alzheimer's disease. Since other ABC transporters regulate adult neurogenesis, we assessed neurogenesis in wild-type (WT) and Abca7 deficient mice. Abca7 deletion did not affect adult neurogenesis in the mouse.


2004 ◽  
Vol 32 (1) ◽  
pp. 124-127 ◽  
Author(s):  
B.L. Knight

The ATP-binding cassette transporter A1 (ABCA1) is involved in the regulation of cholesterol efflux from cells. Mutations in ABCA1 give rise to familial high-density lipoprotein (HDL) deficiency and Tangier disease, which is characterized by very low levels of HDL in plasma and cholesteryl ester accumulation in tonsils and other reticuloendothelial cells. The mechanism of action of ABCA1 is still unclear, but requires the transfer of phospholipid and cholesterol to apolipoprotein A1 bound by or close to the transporter. An important factor in the regulation of ABCA1 is cholesterol itself, which provides oxysterol ligands for liver X receptors that stimulate ABCA1 transcription. ABCA1-deficient mice show increased cholesterol absorption, suggesting that ABCA1 could also help to transport dietary cholesterol back out of intestinal absorptive cells into the lumen. Thus ABCA1 is intimately connected to various aspects of the regulation of whole-body cholesterol metabolism and probably plays an important role in protecting against the development of cardiovascular disease.


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