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
CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
- Primary structure
- Secondary structure
- Tertiary structure
- Quaternary structure
Protein Aminoacids Percentage
SYNTHESIS AND TURNOVER
- Cell signaling and Ligand transport
- Structural proteins
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.
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 . Metformin and TZDs activate AMPK probably via the respiratory chain in mitochondria , and AICAR stimulates AMPK. AMPK controls protein activity by phosphorylation (e.g., inhibits PPARγ by phosphorylation ). Adiponectin activates AdipoR1 and AdipoR2 receptors which act on metabolism via AMPK (AdipoR1) or PPARα (AdipoR2)
HMG-CoA reductase inhibitors (statins) activate expression of PPARalpha/PPARgamma and ABCA1 in cultured gallbladder epithelial cells. 2010
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. firstname.lastname@example.org
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.