Cholesterol ABC-Transporters
ABC-transporter

Author: Gianpiero Pescarmona
Date: 08/04/2010

Description

DEFINITION

ABCA1 export to HDL apolipoproteins apoA-I and apoA-IV (Purification and ATPase Activity of Human ABCA1, 2006)
ABCG1 export to HDL (macrophages)

External links not available on Wikipedia have to be added here

DatabaseLink
WikigenesABCA1ABCG1MDR1/ABCB1
GeneCards"ABCA1":"ABCG1":"MDR1/ABCB1":

CHEMICAL STRUCTURE AND IMAGES

When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage

SYNTHESIS AND TURNOVER

mRNA synthesis
protein synthesis
post-translational modifications
degradation

CELLULAR FUNCTIONS

cellular localization,
biological function

REGULATION

Hexarelin Signaling to PPARγ in Metabolic Diseases, 2008

A GHRP-PPARγ pathway in macrophages. Overview of the effects of hexarelin which by interacting with scavenger receptor CD36 and GHS-R1a ghrelin receptor promotes the transcriptional activation of PPARγ. LXRα which is a target of PPARγ is then upregulated with the subsequent increase in apolipoprotein E (apoE) and sterol transporters ABCA1 and ABCG1 expression. Activation of the PPARγ-LXRα-ABC metabolic pathway in response to hexarelin favors cholesterol efflux by macrophages through high density lipoproteins (HDL)

Hexarelin promotes mitochondrial activity in adipocytes. Scheme of gene expression analysis of fatty acid metabolic regulators in 3T3-L1 adipocytes. Shown are a subset of genes identified as upregulated (red) or downregulated (green) by hexarelin compared to untreated cells. These effects of hexarelin require CD36 which is expressed in adipocytes as opposed to GHS-R1a receptor; FAO, fatty acid oxidation; FABP, fatty acid binding protein; FAS, fatty acid synthase; HSL, hormone-sensitive lipase; ACO, acyl CoA oxidase; ACS, and acyl CoA synthase.

Regulation of Bile Acid and Cholesterol Metabolism by PPARs 2009

Role of the Peroxisome Proliferator-Activated Receptors, Adenosine Monophosphate-Activated Kinase, and Adiponectin in the Ovary 2008

Two fuel sensors integrate energy control and lipid and glucose homeostasis.

  • PPARs, a superfamily of nuclear receptors
  • the kinase AMPK

Adiponectin, one of the adipocyte-derived factors mediate its actions through the AMPK or PPARs pathway. These three molecules are expressed in the ovary, raising questions about the biological actions of fuel sensors in fertility and the use of these molecules to treat fertility problems

Schema illustrating the putative functional interactions between PPARs, AMPK, and adiponectin. PPARγ is activated by binding with PGJ2 or TZDs and PPARα with fibrates or WY 14 463. They control gene transcription, and, in particular, PPARγ ligands increase adiponectin expression [49]. Metformin and TZDs activate AMPK probably via the respiratory chain in mitochondria [22], and AICAR stimulates AMPK. AMPK controls protein activity by phosphorylation (e.g., inhibits PPARγ by phosphorylation [35]). Adiponectin activates AdipoR1 and AdipoR2 receptors which act on metabolism via AMPK (AdipoR1) or PPARα (AdipoR2)

Statins

HIGH

HMG-CoA reductase inhibitors (statins) activate expression of PPARalpha/PPARgamma and ABCA1 in cultured gallbladder epithelial cells. 2010

LOW

Papers statin ABCG1

Atorvastatin inhibits ABCA1 expression and cholesterol efflux in THP-1 macrophages by an LXR-dependent pathway. 2008

Pharmacogenomics. 2009 Jun;10(6):997-1005.
ABCA1 expression and statins: inhibitory effect in peripheral blood mononuclear cells. 2009

Genvigir FD, Hirata MH, Hirata RD.

Department of Clinical & Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, Avenue Professor Lineu Prestes, 580, B.17, 05508-900, Sao Paulo, Brazil. fabidalla@usp.br
Abstract

The ATP-binding cassette transporter A1 (ABCA1) has an essential role in the formation of nascent high-density lipoprotein particles and also participates in the cholesterol efflux from macrophages in the artery wall. Several substances, such as statins, or even gene variants are able to modulate ABCA1 expression. There is strong evidence that statin treatment downregulates the ABCA1 expression in nonloaded macrophages. Interestingly, in cholesterol-loaded macrophages, which are more relevant to atherogenesis, this effect is lost. We observed an inhibitory effect of atorvastatin in peripheral blood mononuclear cells of hypercholesterolemic individuals. Moreover, in these individuals, the ABCA1 -14C>T polymorphism was associated with high baseline gene-expression levels. Other studies are needed to evaluate how relevant these findings are to the formation of arterial foam cells in vivo.

DIAGNOSTIC USE

Comments
2011-02-18T14:58:11 - Gianpiero Pescarmona

Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1. 2006

Early senescence in heterozygous ABCA1 mutation skin fibroblasts: a gene dosage effect beyond HDL deficiency? 2014

  • PURPOSE:
    Homozygous ABCA1 gene mutation causes Tangier disease (TD). The effects reported in heterozygous state regard plasma HDL, cell cholesterol efflux and coronary artery disease. We investigated whether in vitro replicative skin fibroblast senescence shown in TD proband (Hom), his father (Het), and in a healthy control might be induced in a "gene-dosage way".
    METHODS:
    Senescence was evaluated by staining test for β-Galactosidase and telomere length (TL) on fibroblast DNA at different replicative stages. ABCG1 and LDLR (low density lipoprotein receptor) gene expression was also evaluated.
    RESULTS:
    Hom cells showed early senescent morphology and reduced growth at all passages in vitro. The cell positive percentage for β-Galactosidase test was highly increased in Hom compared to Het cells at late replicative status (66.1% vs 41.3% respectively). TL was significantly shorter at high stage either in Hom (p<0.0001) or in Het (p<0.005). At early replication cycles ABCG1 gene expression was about 3-fold higher in Hom compared to Het cells (0.44 vs 0.14 arbitrary unit).
    CONCLUSIONS:
    ABCA1 gene mutation may have "gene-dosage way" effect on in vitro fibroblast senescence. Furthermore, increased ABCG1 and LDLR gene expression could highlight a role of ABCA1 on cytoskeleton regulation associated to cell cholesterol metabolism.
Attachments
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ABCA1_ETC_700.gifgp08/04/2010
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