DOCSLIB.ORG

Apolipoprotein A-I: Structure-Function Relationships Philippe Frank, Yves Marcel

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Apolipoprotein A-I: Structure-Function Relationships Philippe Frank, Yves Marcel Apolipoprotein A-I: structure-function relationships Philippe Frank, Yves Marcel To cite this version: Philippe Frank, Yves Marcel. Apolipoprotein A-I: structure-function relationships. Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, 2000, 41. hal-02460786 HAL Id: hal-02460786 https://hal.archives-ouvertes.fr/hal-02460786 Submitted on 30 Jan 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. review Apolipoprotein A-I: structure–function relationships Philippe G. Frank1 and Yves L. Marcel2 Lipoprotein & Atherosclerosis Group, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7 Abstract The inverse relationship between high density lipo- Supplementary key words reverse cholesterol transport • apolipopro- protein (HDL) plasma levels and coronary heart disease has tein A-I mutants • HDL • cholesterol efflux • LCAT been attributed to the role that HDL and its major constitu- ent, apolipoprotein A-I (apoA-I), play in reverse cholesterol Downloaded from transport (RCT). The efficiency of RCT depends on the spe- cific ability of apoA-I to promote cellular cholesterol efflux, This review focuses on the identification of apoA-I bind lipids, activate lecithin:cholesterol acyltransferase structural domains and their participation to HDL RCT. (LCAT), and form mature HDL that interact with specific We will summarize the current knowledge on apoA-I receptors and lipid transfer proteins. From the intensive structural domains and more particularly their function in analysis of apoA-I secondary structure has emerged our cur- lipid binding and formation of HDL, their contributions www.jlr.org rent understanding of its different classes of amphipathic to cellular cholesterol efflux, and their role in LCAT acti- ␣-helices, which control lipid-binding specificity. The main challenge now is to define apoA-I tertiary structure in its vation. In each case, a particular emphasis will be placed lipid-free and lipid-bound forms. Two models are consid- on the study of apoA-I mutants and the analysis of struc- at Thomas Jefferson Univ on January 24, 2008 ered for discoidal lipoproteins formed by association of tural and functional domains. two apoA-I with phospholipids. In the first or picket fence model, each apoA-I wraps around the disc with antiparallel adjacent ␣-helices and with little intermolecular interac- 1. APOLIPOPROTEIN A-I STRUCTURE tions. In the second or belt model, two antiparallel apoA-I are paired by their C-terminal ␣-helices, wrap around the AND HDL FORMATION lipoprotein, and are stabilized by multiple intermolecular in- Apolipoprotein A-I was one of the first apolipoproteins teractions. While recent evidence supports the belt model, other models, including hybrid models, cannot be ex- to be identified and characterized. Yet its structural char- cluded. ApoA-I ␣-helices control lipid binding and associa- acterization, notably in the lipid-associated form, has not tion with varying levels of lipids. The N-terminal helix 44– been achieved and the domains involved in its multiple 65 and the C-terminal helix 210–241 are recognized as im- functions are not yet fully identified. portant for the initial association with lipids. In the central domain, helix 100–121 and, to a lesser extent, helix 122– A. Primary structure and physicochemical 143, are also very important for lipid binding and the for- properties of apoA-I mation of mature HDL, whereas helices between residues The sequence of apoA-I was determined by Brewer et 144 and 186 contribute little. The LCAT activation domain al. (1), and followed by cloning and characterization of its has now been clearly assigned to helix 144–165 with second- cDNA (2–5) and genomic DNA (6, 7). The gene encod- ary contribution by helix 166–186. The lower lipid binding affinity of the region 144–186 may be important to the acti- ing apoA-I is a member of the apolipoprotein multigene vation mechanism allowing displacement of these apoA-I superfamily, which includes genes encoding exchange- helices by LCAT and presentation of the lipid substrates. No specific sequence has been found that affects diffu- sional efflux to lipid-bound apoA-I. In contrast, the C-terminal helices, known to be important for lipid binding and main- Abbreviations: ABC1, ATP-binding cassette transporter 1; apoA-I, tenance of HDL in circulation, are also involved in the inter- apolipoprotein A-I; CE, cholesteryl ester; CETP, cholesterol ester trans- action of lipid-free apoA-I with macrophages and specific fer protein; DMPC, dimyristoyl phosphatidylcholine; FC, free choles- lipid efflux. While much progress has been made, other as- terol; GdnHCl, guanidine hydrochloride; HDL, high density lipopro- pects of apoA-I structure–function relationships still need tein; LCAT, lecithin:cholesterol acyltransferase; LpA-I, apoA-I-containing to be studied, particularly its lipoprotein topology and its in- lipoproteins; POPC, 1-palmitoyl 2-oleylphosphatidylcholine, RCT, re- teraction with other enzymes, lipid transfer proteins and re- verse cholesterol transport; SR-BI, scavenger receptor class B type I. 1 Present address: Albert Einstein College of Medicine, Department ceptors important for HDL metabolism.—Frank, P. G., and of Molecular Pharmacology, 1300 Morris Park Avenue, The Bronx, NY, Y. L. Marcel. Apolipoprotein A-I: structure–function rela- 10461. tionships. J. Lipid Res. 2000. 41: 853–872. 2 To whom correspondence should be addressed. Journal of Lipid Research Volume 41, 2000 853 Downloaded from www.jlr.org at Thomas Jefferson Univ on January 24, 2008 Fig. 1. 854 Journal of Lipid Research Volume 41, 2000 able apolipoproteins (apoA-I, A-II, Cs, and E) (8). They HCl, urea, or calorimetric denaturation experiments, a are thought to have evolved from a common ancestor by low free energy of denaturation about 2.2–2.7 kcal/mol duplication/deletion of a 33-mer motif. has been determined (22, 23). This value is much lower Analysis of the secondary structure of mature apoA-I than the value determined for globular proteins (in the has allowed the identification of 11- and 22-mer repeats range of 5–10 kcal/mol) (24, 25). This observation is in (9, 10). The 22-mer repeats, usually separated by Pro resi- agreement with a loosely folded and relatively flexible dues, have been associated with the formation of amphi- structure of the protein in the lipid-free form. This loosely pathic ␣-helices (11), which allow the interaction of the folded conformation may allow rapid lipid-interaction of protein with phospholipids through its hydrophobic face, exposed hydrophobic portions of the protein. In support while the hydrophilic face of the helices interacts with the of this view, thermal denaturation experiments by Gursky aqueous phase. and Atkinson have suggested a molten globular-like state ApoA-I sequences from a number of species have been for lipid-free apoA-I that may explain its lipid-binding determined (Fig. 1), with sizes ranging between 258 and properties in vivo (26). Sedimentation velocity experi- 267 amino acids (mature protein plus pre-pro segment). ments on human apoA-I indicate significant conforma- Comparison of sequences amongst mammals indicates tional heterogeneity, which also support a flexible struc- that the N-terminal domain of apoA-I is highly conserved ture (27). This observation may be relevant in the case of while the central and C-terminal domains show conserva- pre␤1-HDL, which has been shown to be the earliest ac- tive substitutions between species. This result is consistent ceptor of cellular cholesterol (28) and appears to contain with the study of Collet et al. (12), who showed, using only 1–2 molecules of partially lipidated apoA-I (29). The Downloaded from mAbs to human apoA-I, that the antigenicity of this pro- N-terminal sequence (residues 1–43) of apoA-I, appar- tein is better conserved between species in the N-terminal ently not required for lipid binding, may be important for domain (residues 1 to 98 of the mature protein). These the stabilization of lipid-free apoA-I in solution (30, 31). observations are in accord with the major role this do- Site directed mutagenesis of tryptophans and fluores- main plays in the structure and/or function of human cence studies show that in the lipid-free state the apoA-I apoA-I. As described in the latter sections of this review, monomer is a prolate ellipsoid and its tryptophans exist in www.jlr.org the N- and C-terminal domains of apoA-I have been in- nonpolar environments compatible with an N-terminal volved in the binding of lipids, an essential function of half that is organized into a bundle of helices (32). this apolipoprotein (13–15). The central domain of the Two cysteine mutants (D9C and A232C) have been at Thomas Jefferson Univ on January 24, 2008 protein, which has been involved in LCAT activation, may studied by circular dichroism and fluorescence spectro- have evolved in parallel with the LCAT sequence in the photometry. The adduct formed with the thiol reactive corresponding species. However, in species in which this probe acrylodan affects the structure and stability of the domain has evolved faster than in humans (mouse and lipid-free D9C mutant but not that of the mutant A234C. rat), the ability of mouse apoA-I to activate mouse LCAT is The fluorescence analysis showed rigid N- and C-terminal reduced as compared to that of human apoA-I (16, 17). structures of the lipid-free apoA-I and a fold that brings Despite changes in the primary structure of apoA-I amongst the C-terminus close to the tryptophans of the N-terminal different species, the secondary structure appears unmod- half (33).
Load more

Recommended publications
  • Heterozygous ATP-Binding Cassette Transporter G5 Gene Deficiency and Risk of Coronary Artery Disease
    bioRxiv preprint doi: https://doi.org/10.1101/780734; this version posted September 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Heterozygous ATP-binding Cassette Transporter G5 Gene Deficiency and Risk of Coronary Artery Disease Short title: Heterozygous ABCG5 deficiency and risk of CAD Akihiro Nomura*, MD PhD, Connor A. Emdin*, DPhil, Hong Hee Won, PhD, Gina M. Peloso, PhD, Pradeep Natarajan, MD, Diego Ardissino, MD, John Danesh, FRCP DPhil, Heribert Schunkert, MD, Adolfo Correa, MD PhD, Matthew J. Bown, MD FRCS, Nilesh J. Samani, MD FRCP, Jeanette Erdmann, PhD, Ruth McPherson, MD, Hugh Watkins, MD PhD, Danish Saleheen, MD, Roberto Elosua, MD PhD, Masa-aki Kawashiri, MD PhD, Hayato Tada, MD PhD, Namrata Gupta, PhD, Svati H. Shah, MD MHS, Daniel J. Rader, MD, Stacey Gabriel, PhD, Amit V. Khera*, MD, Sekar Kathiresan*, MD *: These authors contributed equally Address for correspondence: Sekar Kathiresan, MD Verve Therapeutics 26 Landsdowne Street, 1st Floor Cambridge, MA 02139 Email: [email protected] Phone: 617 603 0070 bioRxiv preprint doi: https://doi.org/10.1101/780734; this version posted September 27, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Background: Familial sitosterolemia is a rare, recessive Mendelian disorder characterized by hyperabsorption and decreased biliary excretion of dietary sterols.
    [Show full text]
  • The Effect of Statin Treatment on Intratumoral Cholesterol Levels and LDL Receptor Expression: a Window-Of-Opportunity Breast Ca
    Feldt et al. Cancer & Metabolism (2020) 8:25 https://doi.org/10.1186/s40170-020-00231-8 RESEARCH Open Access The effect of statin treatment on intratumoral cholesterol levels and LDL receptor expression: a window-of- opportunity breast cancer trial Maria Feldt1,2* , Julien Menard1, Ann H. Rosendahl1,2, Barbara Lettiero1, Pär-Ola Bendahl1, Mattias Belting1,2,3 and Signe Borgquist1,4 Abstract Background: Deregulated lipid metabolism is common in cancer cells and the mevalonate pathway, which synthesizes cholesterol, is central in lipid metabolism. This study aimed to assess statin-induced changes of the intratumoral levels of cholesterol and the expression of the low-density lipoprotein receptor (LDLR) to enhance our understanding of the role of the mevalonate pathway in cancer cholesterol metabolism. Methods: This study is based on a phase II clinical trial designed as a window-of-opportunity trial including 50 breast cancer patients treated with 80 mg of atorvastatin/day for 2 weeks, between the time of diagnosis and breast surgery. Lipids were extracted from frozen tumor tissue sampled pre- and post-atorvastatin treatment. Intratumoral cholesterol levels were measured using a fluorometric quantitation assay. LDLR expression was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded tumor tissue. Paired blood samples pre- and post- atorvastatin were analyzed for circulating low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1, and apolipoprotein B. In vitro experiments on MCF-7 breast cancer cells treated with atorvastatin were performed for comparison on the cellular level. Results: In the trial, 42 patients completed all study parts. From the paired tumor tissue samples, assessment of the cholesterol levels was achievable for 14 tumors, and for the LDLR expression in 24 tumors.
    [Show full text]
  • Participation of ABCA1 Transporter in Pathogenesis of Chronic Obstructive Pulmonary Disease
    International Journal of Molecular Sciences Review Participation of ABCA1 Transporter in Pathogenesis of Chronic Obstructive Pulmonary Disease Stanislav Kotlyarov Department of Nursing, Ryazan State Medical University, 390026 Ryazan, Russia; [email protected] Abstract: Chronic obstructive pulmonary disease (COPD) is the important medical and social problem. According to modern concepts, COPD is a chronic inflammatory disease, macrophages play a key role in its pathogenesis. Macrophages are heterogeneous in their functions, which is largely determined by their immunometabolic profile, as well as the features of lipid homeostasis, in which the ATP binding cassette transporter A1 (ABCA1) plays an essential role. The objective of this work is the analysis of the ABCA1 protein participation and the function of reverse cholesterol transport in the pathogenesis of COPD. The expression of the ABCA1 gene in lung tissues takes the second place after the liver, which indicates the important role of the carrier in lung function. The participation of the transporter in the development of COPD consists in provision of lipid metabolism, regulation of inflammation, phagocytosis, and apoptosis. Violation of the processes in which ABCA1 is involved may be a part of the pathophysiological mechanisms, leading to the formation of a heterogeneous clinical course of the disease. Keywords: chronic obstructive pulmonary disease; COPD; inflammation; ABCA1; reverse cholesterol transport; innate immune system Citation: Kotlyarov, S. Participation of ABCA1 Transporter in Pathogenesis of Chronic Obstructive 1. Introduction Pulmonary Disease. Int. J. Mol. Sci. Chronic obstructive pulmonary disease (COPD) is one of the most widespread dis- 2021, 22, 3334. https://doi.org/ eases, it has great medical significance due to the high frequency of temporary and per- 10.3390/ijms22073334 sistent disability and mortality.
    [Show full text]
  • 1 CETP Inhibition Improves HDL Function but Leads to Fatty Liver and Insulin Resistance in CETP-Expressing Transgenic Mice on A
    Page 1 of 55 Diabetes CETP inhibition improves HDL function but leads to fatty liver and insulin resistance in CETP-expressing transgenic mice on a high-fat diet Lin Zhu1,2, Thao Luu2, Christopher H. Emfinger1,2, Bryan A Parks5, Jeanne Shi2,7, Elijah Trefts3, Fenghua Zeng4, Zsuzsanna Kuklenyik5, Raymond C. Harris4, David H. Wasserman3, Sergio Fazio6 and John M. Stafford1,2,3,* 1VA Tennessee Valley Healthcare System, 2Division of Diabetes, Endocrinology, & Metabolism, 3Department of Molecular Physiology and Biophysics, 4Devision of Nephrology and Hypertension, Vanderbilt University School of Medicine. 5Division of Laboratory Sciences, Centers for Disease Control and Prevention. 6The Center for Preventive Cardiology at the Knight Cardiovascular Institute, Oregon Health & Science University. 7Trinity College of Art and Science, Duke University. * Address correspondence and request for reprints to: John. M. Stafford, 7445D Medical Research Building IV, Nashville, TN 37232-0475, phone (615) 936-6113, fax (615) 936- 1667 Email: [email protected] Running Title: CETP inhibition and insulin resistance Word Count: 5439 Figures: 7 Tables: 1 1 Diabetes Publish Ahead of Print, published online September 13, 2018 Diabetes Page 2 of 55 Abstract In clinical trials inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels but doesn’t robustly improve cardiovascular outcomes. About 2/3 of trial participants were obese. Lower plasma CETP activity is associated with increased cardiovascular risk in human studies, and protective aspects of CETP have been observed in mice fed a high-fat diet (HFD) with regard to metabolic outcomes. To define if CETP inhibition has different effects depending on the presence of obesity, we performed short- term anacetrapib treatment in chow- and HFD-fed CETP-transgenic mice.
    [Show full text]
  • An Abundant Dysfunctional Apolipoprotein A1 in Human Atheroma
    Cleveland State University EngagedScholarship@CSU Mathematics Faculty Publications Mathematics Department 2-1-2014 An Abundant Dysfunctional Apolipoprotein A1 in Human Atheroma Ying Huang Cleveland Clinic Joseph A. DiDonato Cleveland State University, [email protected] Bruce S. Levison Cleveland Clinic Dave Schmitt Cleveland Clinic Lin Li Cleveland Clinic Follow this and additional works at: https://engagedscholarship.csuohio.edu/scimath_facpub Part of the Mathematics Commons See next page for additional authors How does access to this work benefit ou?y Let us know! Repository Citation Huang, Ying; DiDonato, Joseph A.; Levison, Bruce S.; Schmitt, Dave; Li, Lin; Wu, Yuping; Buffa, Jennifer; Kim, Timothy; Gerstenecker, Gary S.; Gu, Xiaodong; Kadiyala, Chandra S.; Wang, Zeneng; Culley, Miranda K.; Hazen, Jennie E.; DiDonato, Anthony J.; Fu, Xiaoming; Berisha, Stela Z.; Peng, Daoquan; Nguyen, Truc T.; Liang, Shaohong; Chuang, Chia-Chi; Cho, Leslie; PLow, Edward F.; Fox, Paul L.; Gogonea, Valentin; Tang, W.H. Wilson; Parks, John S.; Fisher, Edward A.; Smith, Jonathan D.; and Hazen, Stanley L., "An Abundant Dysfunctional Apolipoprotein A1 in Human Atheroma" (2014). Mathematics Faculty Publications. 161. https://engagedscholarship.csuohio.edu/scimath_facpub/161 This Article is brought to you for free and open access by the Mathematics Department at EngagedScholarship@CSU. It has been accepted for inclusion in Mathematics Faculty Publications by an authorized administrator of EngagedScholarship@CSU. For more information, please contact [email protected]. Authors Ying Huang, Joseph A. DiDonato, Bruce S. Levison, Dave Schmitt, Lin Li, Yuping Wu, Jennifer Buffa, Timothy Kim, Gary S. Gerstenecker, Xiaodong Gu, Chandra S. Kadiyala, Zeneng Wang, Miranda K. Culley, Jennie E.
    [Show full text]
  • The Crucial Roles of Apolipoproteins E and C-III in Apob Lipoprotein Metabolism in Normolipidemia and Hypertriglyceridemia
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Harvard University - DASH The crucial roles of apolipoproteins E and C-III in apoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Sacks, Frank M. 2015. “The Crucial Roles of Apolipoproteins E and C-III in apoB Lipoprotein Metabolism in Normolipidemia and Hypertriglyceridemia.” Current Opinion in Lipidology 26 (1) (February): 56–63. doi:10.1097/mol.0000000000000146. Published Version doi:10.1097/MOL.0000000000000146 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:30203554 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Open Access Policy Articles, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#OAP HHS Public Access Author manuscript Author Manuscript Author ManuscriptCurr Opin Author Manuscript Lipidol. Author Author Manuscript manuscript; available in PMC 2016 February 01. Published in final edited form as: Curr Opin Lipidol. 2015 February ; 26(1): 56–63. doi:10.1097/MOL.0000000000000146. The crucial roles of apolipoproteins E and C-III in apoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia Frank M. Sacks Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA Abstract Purpose of review—To describe the roles of apolipoprotein C-III (apoC-III) and apoE in VLDL and LDL metabolism Recent findings—ApoC-III can block clearance from the circulation of apolipoprotein B (apoB) lipoproteins, whereas apoE mediates their clearance.
    [Show full text]
  • Lrp1 Modulators
    Last updated on February 14, 2021 Cognitive Vitality Reports® are reports written by neuroscientists at the Alzheimer’s Drug Discovery Foundation (ADDF). These scientific reports include analysis of drugs, drugs-in- development, drug targets, supplements, nutraceuticals, food/drink, non-pharmacologic interventions, and risk factors. Neuroscientists evaluate the potential benefit (or harm) for brain health, as well as for age-related health concerns that can affect brain health (e.g., cardiovascular diseases, cancers, diabetes/metabolic syndrome). In addition, these reports include evaluation of safety data, from clinical trials if available, and from preclinical models. Lrp1 Modulators Evidence Summary Lrp1 has a variety of essential functions, mediated by a diverse array of ligands. Therapeutics will need to target specific interactions. Neuroprotective Benefit: Lrp1-mediated interactions promote Aβ clearance, Aβ generation, tau propagation, brain glucose utilization, and brain lipid homeostasis. The therapeutic effect will depend on the interaction targeted. Aging and related health concerns: Lrp1 plays mixed roles in cardiovascular diseases and cancer, dependent on context. Lrp1 is dysregulated in metabolic disease, which may contribute to insulin resistance. Safety: Broad-spectrum Lrp1 modulators are untenable therapeutics due to the high potential for extensive side effects. Therapies that target a specific Lrp1-ligand interaction are expected to have a better therapeutic profile. 1 Last updated on February 14, 2021 Availability: Research use Dose: N/A Chemical formula: N/A S16 is in clinical trials MW: N/A Half life: N/A BBB: Angiopep is a peptide that facilitates BBB penetrance by interacting with Lrp1 Clinical trials: S16, an Lrp1 Observational studies: sLrp1 levels are agonist was tested in healthy altered in Alzheimer’s disease, volunteers (n=10) in a Phase 1 cardiovascular disease, and metabolic study.
    [Show full text]
  • Apolipoprotein A4 Gene (APOA4) (Chromosome 11/Haplotypes/Intron Loss/Coronary Artery Disease/Apoal-APOC3 Deficiency) Sotirios K
    Proc. Natl. Acad. Sci. USA Vol. 83, pp. 8457-8461, November 1986 Biochemistry Structure, evolution, and polymorphisms of the human apolipoprotein A4 gene (APOA4) (chromosome 11/haplotypes/intron loss/coronary artery disease/APOAl-APOC3 deficiency) SOTIRios K. KARATHANASIS*t, PETER OETTGEN*t, ISSAM A. HADDAD*t, AND STYLIANOS E. ANTONARAKISt *Laboratory of Molecular and Cellular Cardiology, Department of Cardiology, Children's Hospital and tDepartment of Pediatrics, Harvard Medical School, Boston, MA 02115; and tDepartment of Pediatrics, Genetics Unit, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205 Communicated by Donald S. Fredrickson, July 11, 1986 ABSTRACT The genes coding for three proteins of the APOC3 deficiency and premature coronary artery disease plasma lipid transport system-apolipoproteins Al (APOAI), (13-15), hypertriglyceridemia (16), and hypoalphalipopro- C3 (APOC3), and A4 (APOA4)-are closely linked and teinemia (17). tandemly organized on the long arm ofhuman chromosome 11. In this report the nucleotide sequence of the human In this study the human APOA4 gene has been isolated and APOA4 gene has been determined. The results suggest that characterized. In contrast to APOAl and APOC3 genes, which the APOAI, APOC3, and APOA4 genes were derived from a contain three introns, the APOA4 gene contains only two. An common evolutionary ancestor and indicate that during intron interrupting the 5' noncoding region of the APOA1 and evolution the APOA4 gene lost one of its ancestral introns. APOC3 mRNAs is absent from the corresponding position of Screening of the APOA4 gene region for polymorphisms the APOA4 mRNA. However, similar to APOAI and APOC3 showed that two different Xba I restriction endonuclease genes, the introns of the APOA4 gene separate nucleotide sites are polymorphic in Mediterranean and Northern Euro- sequences coding for the signal peptide and the amphipathic pean populations.
    [Show full text]
  • Increased Phospholipid Transfer Protein Activity Associated with the Impaired Cellular Cholesterol Efflux in Type 2 Diabetic Subjects with Coronary Artery Disease
    Tohoku J. Exp. Med., 2007,Cholesterol 213, 129-137 Efflux and PLTP Activity in Diabetes with CAD 129 Increased Phospholipid Transfer Protein Activity Associated with the Impaired Cellular Cholesterol Efflux in Type 2 Diabetic Subjects with Coronary Artery Disease 1,2 2 2 2 3 NEBIL ATTIA, AMEL NAKBI, MAHA SMAOUI, RAJA CHAABA, PHILIPPE MOULIN, 4 4 5 SONIA HAMMAMI, KHALDOUN BEN HAMDA, FRANÇOISE CHANUSSOT and 2 MOHAMED HAMMAMI 1Biology Department, Faculty of Sciences, University November 7th at Carthage, Bizerte, Tunisia 2Biochemistry Laboratory, UR 08-39, Faculty of Medicine, University of Monastir, Monastir, Tunisia 3U11 Cardiovascular Unit, Louis Pradel Hospital and INSERM U585, Lyon, France 4Departments of Internal Medicine (SH) and Cardiology (KBH), Monastir Hospital, Monastir, Tunisia 5INSERM U476, Faculty of Medecine la Timone, University Aix-Marseille II, Marseille, France ATTIA, N., NAKBI, A., SMAOUI, M., CHAABA, R., MOULIN, P., HAMMAMI, S., HAMDA, K.B., CHANUSSOT, F. and HAMMAMI, M. Increased Phospholipid Transfer Protein Activity Associated with the Impaired Cellular Cholesterol Efflux in Type 2 Diabetic Subjects with Coronary Artery Disease. Tohoku J. Exp. Med., 2007, 213 (2), 129-137 ── Reverse cholesterol transport (RCT) is the pathway, by which the excess of cholesterol is removed from peripheral cells to the liver. An early step of RCT is the efflux of free cholesterol from cell membranes that is mediated by high-density lipoproteins (HDL). Phospholipid transfer protein (PLTP) transfers phospholipids between apolipoprotein-B-containing lipo- proteins (i.e., chylomicrons and very low-density lipoproteins) and HDL. PLTP contrib- utes to the HDL maturation and increases the ability of HDL to extract the cellular choles- terol.
    [Show full text]
  • Common Genetic Variations Involved in the Inter-Individual Variability Of
    nutrients Review Common Genetic Variations Involved in the Inter-Individual Variability of Circulating Cholesterol Concentrations in Response to Diets: A Narrative Review of Recent Evidence Mohammad M. H. Abdullah 1 , Itzel Vazquez-Vidal 2, David J. Baer 3, James D. House 4 , Peter J. H. Jones 5 and Charles Desmarchelier 6,* 1 Department of Food Science and Nutrition, Kuwait University, Kuwait City 10002, Kuwait; [email protected] 2 Richardson Centre for Functional Foods & Nutraceuticals, University of Manitoba, Winnipeg, MB R3T 6C5, Canada; [email protected] 3 United States Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705, USA; [email protected] 4 Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; [email protected] 5 Nutritional Fundamentals for Health, Vaudreuil-Dorion, QC J7V 5V5, Canada; [email protected] 6 Aix Marseille University, INRAE, INSERM, C2VN, 13005 Marseille, France * Correspondence: [email protected] Abstract: The number of nutrigenetic studies dedicated to the identification of single nucleotide Citation: Abdullah, M.M.H.; polymorphisms (SNPs) modulating blood lipid profiles in response to dietary interventions has Vazquez-Vidal, I.; Baer, D.J.; House, increased considerably over the last decade. However, the robustness of the evidence-based sci- J.D.; Jones, P.J.H.; Desmarchelier, C. ence supporting the area remains to be evaluated. The objective of this review was to present Common Genetic Variations Involved recent findings concerning the effects of interactions between SNPs in genes involved in cholesterol in the Inter-Individual Variability of metabolism and transport, and dietary intakes or interventions on circulating cholesterol concen- Circulating Cholesterol trations, which are causally involved in cardiovascular diseases and established biomarkers of Concentrations in Response to Diets: cardiovascular health.
    [Show full text]
  • Apoa4 Antibody Cat
    ApoA4 Antibody Cat. No.: 6269 Western blot analysis of ApoA4 in chicken small intestine tissue lysate with ApoA4 antibody at 1 μg/mL Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Chicken, Human ApoA4 antibody was raised against a 20 amino acid synthetic peptide near the carboxy terminus of chicken ApoA4. IMMUNOGEN: The immunogen is located within the last 50 amino acids of ApoA4. TESTED APPLICATIONS: ELISA, WB ApoA4 antibody can be used for detection of ApoA4 by Western blot at 1 μg/mL. APPLICATIONS: Antibody validated: Western Blot in chicken samples. All other applications and species not yet tested. POSITIVE CONTROL: 1) Chicken Small Intestine Lysate Properties PURIFICATION: ApoA4 Antibody is affinity chromatography purified via peptide column. CLONALITY: Polyclonal ISOTYPE: IgG September 24, 2021 1 https://www.prosci-inc.com/apoa4-antibody-6269.html CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: ApoA4 Antibody is supplied in PBS containing 0.02% sodium azide. CONCENTRATION: 1 mg/mL ApoA4 antibody can be stored at 4˚C for three months and -20˚C, stable for up to one STORAGE CONDITIONS: year. As with all antibodies care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures. Additional Info OFFICIAL SYMBOL: APOA4 ALTERNATE NAMES: ApoA4 Antibody: Apolipoprotein A-IV, Apolipoprotein A4, Apo-AIV ACCESSION NO.: NP_990269 PROTEIN GI NO.: 71773110 GENE ID: 337 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References ApoA4 Antibody: Apolipoprotein A4 (also known as ApoA-IV) is a plasma protein that is O- linked glycoprotein after proteolytic processing.
    [Show full text]
  • Role of Myeloperoxidase Mediated Oxidative Modification and Apolipoprotein Composition in High Density Lipoprotein Function
    ROLE OF MYELOPEROXIDASE MEDIATED OXIDATIVE MODIFICATION AND APOLIPOPROTEIN COMPOSITION IN HIGH DENSITY LIPOPROTEIN FUNCTION by ARUNDHATI UNDURTI Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Thesis Advisor: Dr. Stanley L. Hazen Department of Microbiology and Molecular Biology Cell Biology Program CASE WESTERN RESERVE UNIVERSITY August, 2010 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of _____________________________________________________Arundhati Undurti candidate for the ______________________degreePhD *. Alan Levine (signed)_______________________________________________ (chair of the committee) Stanley Hazen ________________________________________________ Jonathan Smith ________________________________________________ Menachem Shoham ________________________________________________ Mark Chance ________________________________________________ ________________________________________________ (date) _______________________06-30-2010 *We also certify that written approval has been obtained for any proprietary material contained therein. For Amma and Nana TABLE OF CONTENTS List of Figures 3 List of Tables 7 Abbreviations 8 Acknowledgements 11 Abstract 13 Chapter I: Introduction Pathogenesis of Atherosclerosis Endothelial Dysfunction 17 Fatty Streak Formation 17 Advanced Lesion Formation 18 Thrombotic Complications 18 Role of Lipoproteins in Atherosclerosis Lipoprotein Classification and Metabolism 19 High Density Lipoprotein 20 Reverse
    [Show full text]