scholarly journals Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 319 ◽  
Author(s):  
Jie Qu ◽  
Chih-Wei Ko ◽  
Patrick Tso ◽  
Aditi Bhargava
Keyword(s):  
Lipid Binding ◽  
Lipid Absorption ◽  
Free Form ◽  
High Density Lipoproteins ◽  
Potential Therapeutic Target ◽  
Multifunctional Protein ◽  
Physiological Processes ◽  
Apolipoprotein A ◽  
Chylomicron Remnants ◽  
Shed Light

Apolipoprotein A-IV (apoA-IV) is a lipid-binding protein, which is primarily synthesized in the small intestine, packaged into chylomicrons, and secreted into intestinal lymph during fat absorption. In the circulation, apoA-IV is present on chylomicron remnants, high-density lipoproteins, and also in lipid-free form. ApoA-IV is involved in a myriad of physiological processes such as lipid absorption and metabolism, anti-atherosclerosis, platelet aggregation and thrombosis, glucose homeostasis, and food intake. ApoA-IV deficiency is associated with atherosclerosis and diabetes, which renders it as a potential therapeutic target for treatment of these diseases. While much has been learned about the physiological functions of apoA-IV using rodent models, the action of apoA-IV at the cellular and molecular levels is less understood, let alone apoA-IV-interacting partners. In this review, we will summarize the findings on the molecular function of apoA-IV and apoA-IV-interacting proteins. The information will shed light on the discovery of apoA-IV receptors and the understanding of the molecular mechanism underlying its mode of action.

Metabolism of apolipoprotein A-I of chylomicrons in rats and humans

1981 ◽  
Vol 59 (8) ◽  
pp. 613-618 ◽  
Author(s):  
Jean-Louis Vigne ◽  
Richard J. Havel
Keyword(s):  
Body Weight ◽  
Elevated Level ◽  
High Density ◽  
High Density Lipoproteins ◽  
Rat Serum ◽  
Apolipoprotein A ◽  
Apo E ◽  
High Concentrations ◽  
Chylomicron Remnants ◽  
Intact Rats

After intravenous injection of a large amount of small chylomicrons into intact rats, the concentration of apolipoprotein (apo) A-I was increased by about 40% and remained at this elevated level as most of the chylomicron triglycerides were removed from plasma during the ensuing hour. This apo A-I rapidly left the chylomicrons and was transferred to lipoproteins of higher density. Such transfer of apo A-I did not occur when chylomicrons were incubated at comparably high concentrations with rat serum. In normolipidemic humans, the concentration of apo A-I and apo A-II, as well as phospholipids, increased in the light subfraction of high density lipoproteins (HDL2) 4 to 7 h after ingestion of a meal containing 1.5 g cream fat per kilogram body weight. The concentration of these components increased in the heavy subfraction of high density lipoproteins (HDL3) after 12 to 24 h. The concentration of apo E in plasma was unaffected by fat ingestion, but the concentration of this protein increased in lipoproteins of density less than 1.006 g∙mL−1 and fell in lipoproteins of higher density. It is concluded that apo A-I in rat chylomicrons is transferred quantitatively to HDL as chylomicron remnants are formed. Chylomicron apo A-I and apo A-II appear to be transferred similarly to HDL in humans, whereas apo E is transferred from HDL to chylomicrons after chylomicrons enter the blood.

scholarly journals Apolipoprotein A-I (ApoA-I), Immunity, Inflammation and Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1097 ◽  
Author(s):  
Georgila ◽  
Vyrla ◽  
Drakos
Keyword(s):  
Cancer Biology ◽  
Animal Studies ◽  
High Density Lipoproteins ◽  
Major Protein ◽  
Multifunctional Protein ◽  
Cancer Pathogenesis ◽  
Early Cancer Diagnosis ◽  
Apolipoprotein A

Apolipoprotein A-I (ApoA-I), the major protein component of high-density lipoproteins (HDL) is a multifunctional protein, involved in cholesterol traffic and inflammatory and immune response regulation. Many studies revealing alterations of ApoA-I during the development and progression of various types of cancer suggest that serum ApoA-I levels may represent a useful biomarker contributing to better estimation of cancer risk, early cancer diagnosis, follow up, and prognosis stratification of cancer patients. In addition, recent in vitro and animal studies disclose a more direct, tumor suppressive role of ApoA-I in cancer pathogenesis, which involves anti-inflammatory and immune-modulatory mechanisms. Herein, we review recent epidemiologic, clinicopathologic, and mechanistic studies investigating the role of ApoA-I in cancer biology, which suggest that enhancing the tumor suppressive activity of ApoA-I may contribute to better cancer prevention and treatment.

scholarly journals Impact of Self-association on Function of Apolipoprotein A-I

2011 ◽  
Vol 286 (41) ◽  
pp. 35610-35623 ◽  
Author(s):  
Shobini Jayaraman ◽  
Sumiko Abe-Dohmae ◽  
Shinji Yokoyama ◽  
Giorgio Cavigiolio
Keyword(s):  
Lipid Binding ◽  
Biologically Active ◽  
High Density Lipoproteins ◽  
Cellular Lipid ◽  
Functional Feature ◽  
Solution Property ◽  
Apolipoprotein A ◽  
Self Association ◽  
Associated Species

Self-association is an inherent property of the lipid-free forms of several exchangeable apolipoproteins, including apolipoprotein A-I (apoA-I), the main protein component of high density lipoproteins (HDL) and an established antiatherogenic factor. Monomeric lipid-free apoA-I is believed to be the biologically active species, but abnormal conditions, such as specific natural mutations or oxidation, produce an altered state of self-association that may contribute to apoA-I dysfunction. Replacement of the tryptophans of apoA-I with phenylalanines (ΔW-apoA-I) leads to unusually large and stable self-associated species. We took advantage of this unique solution property of ΔW-apoA-I to analyze the role of self-association in determining the structure and lipid-binding properties of apoA-I as well as ATP-binding cassette A1 (ABCA1)-mediated cellular lipid release, a relevant pathway in atherosclerosis. Monomeric ΔW-apoA-I and wild-type apoA-I activated ABCA1-mediated cellular lipid release with similar efficiencies, whereas the efficiency of high order self-associated species was reduced to less than 50%. Analysis of specific self-associated subclasses revealed that different factors influence the rate of HDL formation in vitro and ABCA1-mediated lipid release efficiency. The α-helix-forming ability of apoA-I is the main determinant of in vitro lipid solubilization rates, whereas loss of cellular lipid release efficiency is mainly caused by reduced structural flexibility by formation of stable quaternary interactions. Thus, stabilization of self-associated species impairs apoA-I biological activity through an ABCA1-mediated mechanism. These results afford mechanistic insights into the ABCA1 reaction and suggest self-association as a functional feature of apoA-I. Physiologic mechanisms may alter the native self-association state and contribute to apoA-I dysfunction.

Stability of free apolipoprotein A-1 concentration in serum, and its measurement in normal and hyperlipidemic subjects.

1987 ◽  
Vol 33 (7) ◽  
pp. 1163-1169 ◽  
Author(s):  
R H Neary ◽  
E Gowland
Keyword(s):  
Radial Immunodiffusion ◽  
Urea Solution ◽  
Free Form ◽  
High Density Lipoproteins ◽  
Crossed Immunoelectrophoresis ◽  
Apolipoprotein A ◽  
Two Samples ◽  
Reference Serum ◽  
The Mean ◽  
Mean Concentration

Abstract Free apolipoprotein A-1 (free A-1) is a low-molecular-mass complex of protein and lipid containing apolipoprotein A-1 (apo A-1). Using crossed immunoelectrophoresis, we separated free A-1 from the apo A-1 in high-density lipoproteins (HDL) and quantified free A-1 by comparison with a reference serum (containing 1.45 g of apo A-1 per liter) diluted in 9 mol/L urea solution. This latter treatment yields apo A-1 containing protein-lipid complexes of the same size and electrophoretic mobility as free A-1. Within-day precision (CV), determined by replicate analysis of two samples with mean free A-1 concentrations of 48 and 138 mg/L, was 9.1 and 7.2%, respectively. We also showed that the concentration of free A-1 is not stable in serum or plasma either at 4 degrees C or when frozen. The mean concentration of free A-1 in 28 fasted, healthy subjects was 75.3 (SD 13.6) mg/L. The postprandial increase was not statistically significant. The percentage of total apo A-1 in the free form in serum ranged from 3.5% to 8.1%, less than the 10% to 30% reported by others who used radial immunodiffusion to measure free A-1. Because radial immunodiffusion does not separate free A-1 from HDL, we believe that that technique overestimates free A-1. We also used crossed immunoelectrophoresis to measure free A-1 in 76 hyperlipidemic patients. Those with Fredrickson types III and V had significantly increased concentrations of free A-1 (P less than .0001). Correlations between free A-1 and cholesterol and triglycerides in serum were significant (P less than .005 and P less than .001, respectively). Possible roles for free A-1 in lipid metabolism are discussed.

Extracellular Vesicles in Tumor Diagnosis: A Mini-Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Si Yu ◽  
Menglin Huang ◽  
Jingyu Wang ◽  
Yongchang Zheng ◽  
Haifeng Xu
Keyword(s):  
Clinical Diagnosis ◽  
Sensitivity And Specificity ◽  
Cancer Diagnosis ◽  
Cancer Biomarkers ◽  
Related Substances ◽  
Physiological Processes ◽  
Cancer Pathogenesis ◽  
Limited Application ◽  
Low Sensitivity ◽  
Shed Light

: Widely exploration of noninvasive tumor/cancer biomarkers has shed light on clinical diagnosis. However, many under-investigated biomarkers showed limited application potency due to low sensitivity and specificity, while extracellular vehicles (EVs) were gradually recognized as promising candidates. EVs are small vesicles transporting bioactive cargos between cells in multiple physiological processes and also in tumor/cancer pathogenesis. This review aimed to offer recent studies of EVs on structure, classification, physiological functions, as well as changes in tumor initiation and progression. Furthermore, we focused on advances of EVs and/or EV-related substances in cancer diagnosis, and summarized ongoing studies of promising candidates for future investigations.

scholarly journals Importance of Apolipoprotein A-I and A-II Composition in HDL and Its Potential for Studying COVID-19 and SARS-CoV-2

Medicines ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 38
Author(s):  
Kyung-Hyun Cho
Keyword(s):  
Antiviral Activity ◽  
High Density ◽  
High Density Lipoproteins ◽  
Potent Antiviral Activity ◽  
Apolipoprotein A ◽  
Putative Role

The composition and properties of apolipoprotein (apo) A-I and apoA-II in high-density lipoproteins (HDL) might be critical to SARS-CoV-2 infection via SR-BI and antiviral activity against COVID-19. HDL containing native apoA-I showed potent antiviral activity, while HDL containing glycated apoA-I or other apolipoproteins did not. However, there has been no report to elucidate the putative role of apoA-II in the antiviral activity of HDL.

scholarly journals Expression of human apolipoprotein A-II and its effect on high density lipoproteins in transgenic mice.

1992 ◽  
Vol 267 (30) ◽  
pp. 21630-21636 ◽  
Author(s):  
J.R. Schultz ◽  
E.L. Gong ◽  
M.R. McCall ◽  
A.V. Nichols ◽  
S.M. Clift ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
High Density ◽  
High Density Lipoproteins ◽  
Human Apolipoprotein ◽  
Apolipoprotein A
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