Introduction of ABCA1

ABCA1, encoded by ABCA1 gene, belongs to an ATP-binding cassette (ABC) transporters superfamily which transport various molecules across extra- and intracellular membranes. There are seven subfamilies in ABC superfamily named as ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White, respectively. ABCA1 is a member of ABC1 subfamily. It is most expressed in the liver, the small in the intestine and adipose tissue where they are involved in the turnover of lipids.

Function of ABCA1 Membrane Protein

ABCA1, also known as cholesterol efflux regulatory protein (CERP), functions as a cholesterol membrane transporter involved in the regulation of cellular cholesterol and phospholipid homeostasis. It has been shown that ABCA1 mediates the traffic of lipids between Golgi and cell membrane. Moreover, ABCA1 plays an essential role in the formation of nascent high-density lipoproteins (HDL) through controlling cellular efflux of cholesterol and phospholipids into lipid-free apolipoproteins (apo-A1 and apoE). And a number of mutations in ABCA1 are associated with several lipid metabolism disorders, such as familial high-density lipoprotein deficiency, coronary heart disease, and Tangier disease. However, the overexpression of ABCA1 may increase plasma HDL levels and decrease atherosclerosis induced by diet. Studies also found that ABCA1 may be involved in the glucose tolerance and insulin secretion through controlling the cholesterol homeostasis in β-cells. Additionally, ABCA1 may exert a role in the inflammatory response. The deficiency of ABCA1 may strongly increase macrophage inflammatory. And the overexpression of ABCA1 may induce resistance to the anti-inflammatory diarylheptanoid antioxidant curcumin.

Fig. 1 Based on current knowledge, we propose the following interplay between Aβ, ApoE, ABCA1, LRP1, P-gp, MRP1 (and possibly BCRP): Under normal physiological conditions, ABCA1-mediated cholesterol and phospholipid efflux from astrocytes, microglia, neurons (and possibly endothelial cells) facilitates ApoE lipidation. (Andrea, 2012)

Application of ABCA1 Membrane Protein in Literature

1. Dron J.S, et al. Large-scale deletions of the ABCA1 gene in patients with hypoalphalipoproteinemia. Journal of Lipid Research. 2018, 59(8): 1529-1535. PubMed ID: 29866657
   
   

   The study shows that the large-scale deletions in ABCA1 gene (a heterozygous deletion of exon 4, a heterozygous deletion spanning exons 8 to 31, and a heterozygous deletion of the entire ABCA1 gene) are observed in the patients with hypoalphalipoproteinemia.

2. Jung D., et al. Correction: A meta-analysis of the associations between the ATP-binding cassette transporter ABCA1 R219K (rs2230806) polymorphism and the risk of type 2 diabetes in Asians. Hormone and Metabolic Research. 2018, 50(4): 308-316. PubMed ID: 29879747
   
   

   The study indicates that the polymorphism R219K of ABCA1 is associated with the risk of type 2 diabetes in Asians by using a meta-analysis.

3. Sonett J., et al. A critical role for ABC transporters in persistent lung inflammation in the development of emphysema after smoke exposure. FASEB Journal. 2018. PubMed ID: 29906247
   
   

   The research reports that the macrophage inflammatory response induced by cigarette smoke exposure is associated with the mediation of cholesterol pathways. And ABCA1 may act as a therapeutic target for the treatment of chronic obstructive pulmonary disease.

4. Ban N., et al. Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration. Journal of Lipid Research. 2018, 59(8): 1414-1423. PubMed ID: 29946056
   
   

   The study proves that the deficiency of both ABCA1 and ABCG1 in rod photoreceptors results in the age-related accumulation of cholesterol metabolites in the outer retina, photoreceptor dysfunction, degeneration of rod outer segments, and ultimately blindness.

5. Zhou T., et al. ABCA1 is coordinated with ABCB1 in the arsenic-resistance of human cells. Appl Biochem Biotechnol. 2018. PubMed ID: 29951962
   
   

   The study shows that ABCA1 coordinated with ABCB1 promote arsenic resistance in arsenic-resistant ECV-304 (AsRE) cell line.

ABCA1 Preparation Options

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Reference

1. Andrea W, et al. (2012). ABC transporters and the Alzheimer’s disease enigma. Frontiers in Psychiatry. 3(54), 1-14.

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