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Nihon Rinsho. Japanese Journal of... Dec 1994Apolipoproteins A include apoA-I, apoA-II and apoA-IV. These apolipoproteins are involved in the metabolism of HDL and reverse cholesterol transport. The genes encoding... (Review)
Review
Apolipoproteins A include apoA-I, apoA-II and apoA-IV. These apolipoproteins are involved in the metabolism of HDL and reverse cholesterol transport. The genes encoding apoA-I, apoA-II and apoA-IV have arisen from a common ancestor. This review describes the structures of the genes encoding apoA-I, apoA-II and apoA-IV, and the structures and functions of the gene products with special reference to the metabolism of HDL and reverse cholesterol transport. Further studies are required to elucidate the full role of apolipoproteins A, especially apoA-II and apoA-IV in HDL metabolism. Analysis of human genetic deficiency and transgenic animal model will be useful for the elucidation of the functions of apolipoproteins A.
Topics: Amino Acid Sequence; Animals; Apolipoproteins A; Base Sequence; Biological Transport; Cholesterol, HDL; Gene Expression; Humans; Molecular Sequence Data; Phosphatidylcholine-Sterol O-Acyltransferase
PubMed: 7853697
DOI: No ID Found -
Biochimica Et Biophysica Acta Aug 1989The monolayer system was employed to investigate the relative affinities of apolipoproteins A-I and A-II for the lipid/water interface. The adsorption of reductively... (Comparative Study)
Comparative Study
The monolayer system was employed to investigate the relative affinities of apolipoproteins A-I and A-II for the lipid/water interface. The adsorption of reductively 14C-methylated apolipoproteins to phospholipid monolayers spread at the air/water interface was determined by monitoring the surface pressure of the mixed monolayer and the surface concentration of the apoprotein. ApoA-II has a higher affinity than apoA-I for lipid monolayers; for a given initial surface pressure, apoA-II adsorbs more than apoA-I to monolayers of egg phosphatidylcholine (PC), distearoyl-PC and human high-density lipoprotein (HDL3) surface lipids. Comparison of the molecular packing of apolipoproteins A-I and A-II suggests that apoA-II adopts a more condensed conformation at the lipid/water interface compared to apoA-I. The ability of apoA-II to displace apoA-I from egg PC and HDL3 surface lipid monolayers was studied by following the adsorption and desorption of the reductively 14C-methylated apolipoproteins. At saturating subphase concentrations of the apoproteins (3.10(-5) g/100 ml), two molecules of apoA-II absorbed for each molecule of apoA-I displaced. This displacement was accompanied by an increase in surface pressure. An identical stoichiometry for the displacement of apoA-I from HDL particles by apoA-II has been reported by others. At low subphase concentrations of apoproteins (5.10(-6) g/100 ml), the apoA-I/lipid monolayer was not fully compressed and could accommodate the adsorbing apoA-II molecules without displacement of apoA-I molecules. ApoA-I molecules were unable to displace apoA-II from the lipid/water interface. The average residue hydrophobicity of apoA-II is higher than that of apoA-I; this may contribute to the higher affinity of apoA-II for lipids compared to apoA-I. The probable helical regions in apolipoproteins A-I and A-II were located using a secondary structure prediction algorithm. The analysis suggests that the amphiphilic properties of the alpha-helical regions of apoA-I and apoA-II are probably not significantly different. Further understanding of the differences in surface activity of these apolipoproteins will require more knowledge of their secondary and tertiary structures.
Topics: Amino Acid Sequence; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins A; Chemical Phenomena; Chemistry; Humans; Lipid Metabolism; Molecular Sequence Data; Protein Conformation; Surface Properties; Water
PubMed: 2503030
DOI: 10.1016/0005-2760(89)90077-5 -
Journal of Lipid Research Jul 2009The expression of recombinant apolipoproteins provides experimental avenues that are not possible with plasma purified protein. The ability to specifically mutate...
The expression of recombinant apolipoproteins provides experimental avenues that are not possible with plasma purified protein. The ability to specifically mutate residues or delete entire regions has proven to be a valuable tool for understanding the structure and function of apolipoproteins. A common feature of many recombinant systems is an affinity tag that allows for straightforward and high-yield purification of the target protein. A specific protease can then cleave the tag and yield the native recombinant protein. However, the application of this strategy to apolipoproteins has proven somewhat problematic because of the tendency for these highly flexible proteins to be nonspecifically cleaved at undesired sites within the native protein. Although systems have been developed using a variety of proteases, many suffer from low yield and, especially, the high cost of the enzyme.We developed a method that utilizes the tobacco etch virus protease to cleave a histidine-tag from apolipoproteins A-I and A-IV expressed in Escherichia coli. This protease can be easily and inexpensively expressed within most laboratories. We found that the protease efficiently cleaved the affinity tags from both apolipoproteins without nonspecific cleavage. All structural and functional measurements showed that the proteins were equivalent to native or previously characterized protein preparations. In addition to cost-effectiveness, advantages of the tobacco etch virus protease include a short cleavage time, low reaction temperature, and easy removal using the protease's own histidine-tag.
Topics: Amino Acid Sequence; Apolipoprotein A-I; Apolipoproteins A; Endopeptidases; Molecular Sequence Data; Recombinant Proteins
PubMed: 19318686
DOI: 10.1194/jlr.D900003-JLR200 -
Scandinavian Journal of Clinical and... Apr 1985Apolipoproteins A-I, A-II and E were determined in the plasma of nine patients (five females, four males) with cholestatic liver disease (eight patients with primary...
Apolipoproteins A-I, A-II and E were determined in the plasma of nine patients (five females, four males) with cholestatic liver disease (eight patients with primary biliary cirrhosis and one patient with sclerosing cholangitis). Plasma concentrations were measured by electroimmunoassay in the fasting state, postprandially after ingestion of either 100 g fat as whipping cream or a light mixed meal with or without addition of wheat fibre. Concentrations of apolipoproteins A-I and A-II were low in patients with cholestatic liver disease and A-I levels correlated inversely with the severity of liver disease as measured by bilirubin levels (r = -0.66). No changes in plasma apolipoprotein A-I, A-II or E concentrations occurred postprandially. There was an inverse correlation between plasma concentrations of apolipoproteins A-I and E (p less than 0.05, r = -0.68). A close relation existed between the ratio of apolipoprotein E to apolipoprotein A-I and plasma bile salt concentration (r = 0.80, p less than 0.01) and serum bilirubin (r = 0.76, p less than 0.01). This implies that in cholestatic liver disease apolipoprotein E and A-I levels reflect the degree of cholestasis.
Topics: Adult; Aged; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins A; Apolipoproteins E; Cholangitis; Cholestasis, Intrahepatic; Female; Food; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged
PubMed: 3923605
DOI: 10.3109/00365518509160981 -
Nutrition, Metabolism, and... Oct 2005
Topics: Apolipoprotein B-100; Apolipoproteins A; Apolipoproteins B; Cardiovascular Diseases; Humans; Lipoprotein(a); Lipoproteins, LDL
PubMed: 16216717
DOI: 10.1016/j.numecd.2005.07.006 -
Arquivos Brasileiros de Cardiologia Jul 2014The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide... (Review)
Review
The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.
Topics: Apolipoproteins A; Humans; Lipoprotein(a); Risk Factors
PubMed: 25120086
DOI: 10.5935/abc.20140101 -
Journal of Lipid Research Jun 1994The aim of the present study was to determine in vitro the effects of various purified apolipoproteins (apo) on the activity of the cholesteryl ester transfer protein... (Comparative Study)
Comparative Study
The aim of the present study was to determine in vitro the effects of various purified apolipoproteins (apo) on the activity of the cholesteryl ester transfer protein (CETP). It appeared that the ability of apoA-I, A-II, and A-IV to modulate the CETP-mediated transfer of radiolabeled cholesteryl esters between low density lipoproteins (LDL) and high density lipoproteins (HDL) was markedly influenced by the final apolipoprotein:lipoprotein ratio in incubation mixtures. At low apolipoprotein:lipoprotein ratio, the rate of radiolabeled cholesteryl esters transferred from HDL3 to LDL was significantly increased in the presence of apoA-I and apoA-IV. Under similar conditions, the rate of radiolabeled cholesteryl esters transferred from LDL to HDL3 was increased in the presence of apoA-I while apoA-IV had no significant effects. At high apolipoprotein:lipoprotein ratio, the ability of apoA-I and apoA-IV to enhance the rate of radiolabeled cholesteryl esters transferred either from HDL3 to LDL or from LDL to HDL3 was considerably reduced. At the highest apolipoprotein:lipoprotein ratio studied, apoA-I and A-IV became inhibitors of the CETP-mediated transfer reaction. Interestingly, apoA-II differed markedly from other apolipoproteins as, even at a low apolipoprotein:lipoprotein ratio, it significantly inhibited CETP activity as measured either from HDL3 to LDL or from LDL to HDL3. The inhibition by apoA-II was concentration-dependent and, at the highest apolipoprotein:lipoprotein ratio studied, cholesteryl ester transfer activity was totally suppressed. The possibility of a direct interaction between CETP and the two major HDL apolipoproteins, apoA-I and apoA-II, was further investigated by combining crosslinking and immunoblotting techniques. Whereas CETP alone had an apparent molecular mass of 76,000 +/- 3,100 Da, crosslinking reactions in incubation mixtures containing CETP and either apoA-I or apoA-II revealed the appearance of additional protein bands with apparent molecular masses of 99,600 +/- 6,100 and 86,900 +/- 4,500 Da, respectively. These complexes corresponded to the association of one molecule of CETP with one molecule of apoA-I or apoA-II. Interestingly, the mass concentrations of apoA-II needed to produce visible CETP-apolipoprotein complexes appeared to be about ten times higher as compared with apoA-I, suggesting that CETP may have a lower affinity for apoA-II than for apoA-I. In conclusion, data from the present study indicate that apolipoproteins A-I, A-II, and A-IV could be potent modulators of the CETP-mediated transfer of cholesteryl esters between HDL and LDL fractions.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins A; Carrier Proteins; Cholesterol Ester Transfer Proteins; Cholesterol Esters; Glycoproteins; Humans; Lipoproteins, HDL; Lipoproteins, HDL3; Lipoproteins, LDL; Molecular Weight
PubMed: 8077854
DOI: No ID Found -
Minerva Medica Aug 2008The Lp(a) is a low density lipoprotein produced by the liver and it seems to be related to vascular diseases. There is a large individual variability of Lp(a) in the... (Review)
Review
The Lp(a) is a low density lipoprotein produced by the liver and it seems to be related to vascular diseases. There is a large individual variability of Lp(a) in the blood levels in the different subjects. The mechanism of the Lp(a) in the pathogenesis of atherosclerosis is not completely clear. There are a lot of different hypotheses and, one of these, is based on the structural analogy of apo(a) with plasminogen. According to current knowledge, it seems that there is a strong relationship between Lp(a) levels and coronary artery disease. Instead, there are still doubts about the real relationship between Lp(a) and stroke. Furthermore, Lp(a) levels seems to be influenced by some other cardiovascular risk factors: fibrinogen, cigarette smoke, and other. Actually, the dosage of the protein is not very useful in clinical practice.
Topics: Apolipoproteins A; Atherosclerosis; Humans; Kringles; Lipoprotein(a); Risk Factors; Stroke
PubMed: 18663347
DOI: No ID Found -
Pharmacological Research Aug 2020Angiogenesis is a finely co-ordinated, multi-step developmental process of the new vascular structure. Even though angiogenesis is regularly occurring in physiological... (Review)
Review
Angiogenesis is a finely co-ordinated, multi-step developmental process of the new vascular structure. Even though angiogenesis is regularly occurring in physiological events such as embryogenesis, in adults, it is restricted to specific tissue sites where rapid cell-turnover and membrane synthesis occurs. Both excessive and insufficient angiogenesis lead to vascular disorders such as cancer, ocular diseases, diabetic retinopathy, atherosclerosis, intra-uterine growth restriction, ischemic heart disease, stroke etc. Occurrence of altered lipid profile and vascular lipid deposition along with vascular disorders is a hallmark of impaired angiogenesis. Among lipoproteins, lipoprotein(a) needs special attention due to the presence of a multi-kringle protein subunit, apolipoprotein(a) [apo(a)], which is structurally homologous to many naturally occurring anti-angiogenic proteins such as plasminogen and angiostatin. Researchers have constructed different recombinant forms of apo(a) (rhLK68, rhLK8, RHACK2, KV-11, and AU-6) and successfully exploited its potential to inhibit unwanted angiogenesis during tumor metastasis and retinal neovascularization. Similar to naturally occurring anti-angiogenic proteins, apo(a) can directly interfere with angiogenic signaling pathways. Besides this, apo(a) can also exert its anti-angiogenic effect indirectly by inducing endothelial cell apoptosis, by inhibiting endothelial progenitor cell functions or by upregulating nuclear factors in endothelial cells via apo(a)-bound oxPLs. However, the impact of the anti-angiogenic potential of native apo(a) during physiological angiogenesis in embryos and wounded tissues is not yet explored. In this context, we review the studies so far done to demonstrate the anti-angiogenic activity of apo(a) and the recent developments in using apo(a) as a therapeutic agent to treat impaired angiogenesis during vascular disorders, with emphasis on the gaps in the literature.
Topics: Angiogenesis Inhibitors; Animals; Apolipoproteins A; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic
PubMed: 32430285
DOI: 10.1016/j.phrs.2020.104858 -
Methods in Enzymology 1986A number of different analytical techniques are now available for the isolation of apoA-I, apoA-II, and apoA-IV. The choice of a particular technique is dependent on the...
A number of different analytical techniques are now available for the isolation of apoA-I, apoA-II, and apoA-IV. The choice of a particular technique is dependent on the instrumentation available, and the quantity of isolated apolipoprotein required. The isolation and characterization of the separate isoforms and the precursor isoproteins of the individual apolipoproteins are detailed, and methods for the evaluation of the purity of the separate apolipoproteins presented. A method for the evaluation of apolipoproteins in plasma is now available which permits the identification of structural variants of plasma apolipoproteins in patients with dyslipoproteinemias.
Topics: Amino Acid Sequence; Amino Acids; Animals; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins A; Chromatography, High Pressure Liquid; Dogs; Electrophoresis, Polyacrylamide Gel; Humans; Immunodiffusion; Isoelectric Focusing; Lipoproteins, HDL; Polymorphism, Genetic
PubMed: 3088390
DOI: 10.1016/0076-6879(86)28070-2