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Apoproteins
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Eugene A Podrez – One of the best experts on this subject based on the ideXlab platform.
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cross linking modifications of hdl Apoproteins by oxidized phospholipids structural characterization in vivo detection and functional implications
Journal of Biological Chemistry, 2020Co-Authors: Detao Gao, Mohammad Z Ashraf, Lifang Zhang, Niladri Kar, Tatiana V Byzova, Eugene A PodrezAbstract:Apolipoprotein A-I (apoA-I) is cross-linked and dysfunctional in human atheroma. Although multiple mechanisms of apoA-I cross-linking have been demonstrated in vitro, the in vivo mechanisms of cross-linking are not well-established. We have recently demonstrated the highly selective and efficient modification of high-density lipoprotein (HDL) Apoproteins by endogenous oxidized phospholipids (oxPLs), including γ-ketoalkenal phospholipids. In the current study, we report that γ-ketoalkenal phospholipids effectively cross-link Apoproteins in HDL. We further demonstrate that cross-linking impairs the cholesterol efflux mediated by apoA-I or HDL3 in vitro and in vivo Using LC-MS/MS analysis, we analyzed the pattern of apoprotein cross-linking in isolated human HDL either by synthetic γ-ketoalkenal phospholipids or by oxPLs generated during HDL oxidation in plasma by the physiologically relevant MPO-H2O2-NO2- system. We found that five histidine residues in helices 5-8 of apoA-I are preferably cross-linked by oxPLs, forming stable pyrrole adducts with lysine residues in the helices 3-4 of another apoA-I or in the central domain of apoA-II. We also identified cross-links of apoA-I and apoA-II with two minor HDL Apoproteins, apoA-IV and apoE. We detected a similar pattern of apoprotein cross-linking in oxidized murine HDL. We further detected oxPL cross-link adducts of HDL Apoproteins in plasma and aorta of hyperlipidemic LDLR-/- mice, including cross-link adducts of apoA-I His-165-apoA-I Lys-93, apoA-I His-154-apoA-I Lys-105, apoA-I His-154-apoA-IV Lys-149, and apoA-II Lys-30-apoE His-227. These findings suggest an important mechanism that contributes to the loss of HDL’s atheroprotective function in vivo.
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characterization of covalent modifications of hdl Apoproteins by endogenous oxidized phospholipids
Free Radical Biology and Medicine, 2017Co-Authors: Detao Gao, Eugene A PodrezAbstract:Abstract High density lipoprotein (HDL) is cardioprotective, unless it is pathologically modified under oxidative stress. Covalent modifications of lipid-free apoA-I, the most abundant apoprotein in HDL, compromise its atheroprotective functions. HDL is enriched in oxidized phospholipids (oxPL) in vivo in oxidative stress. Furthermore, oxidized phospholipids can covalently modify HDL Apoproteins. We have now carried out a systematic analysis of modifications of HDL Apoproteins by endogenous oxPL. Human HDL or plasma were oxidized using a physiologically relevant MPO−H2O2−NO2− system or AIPH, or were exposed to synthetic oxPL. Protein adduction by oxPL was assessed using LC-MS/MS and MALDI-TOF MS. The pattern of HDL apoprotein modification by oxPL was independent of the oxidation systems used. ApoA-I and apoA-II were the major modification targets. OxPL with a γ-hydroxy (or oxo)-alkenal were mostly responsible for modifications, and the Michael adduct was the most abundant adduct. Histidines and lysines in helices 5–8 of apoA-I were highly susceptible to oxPL modifications, while lysines in helices 1, 2, 4 and 10 were resistant to modification by oxPL. In plasma exposed to oxidation or synthetic oxPL, oxPL modification was highly selective, and four histidines (H155, H162, H193 and H199) in helices 6–8 of apoA-I were the main modification target. H710 and H3613 in apoB-100 of LDL and K190 of human serum albumin were also modified by oxPL but to a lesser extent. Comparison of oxPL with short chain aldehyde HNE using MALDI-TOF MS demonstrated high selectivity and efficiency of oxPL in the modification of HDL Apoproteins. These findings provide a novel insight into a potential mechanism of the loss of atheroprotective function of HDL in conditions of oxidative stress.
Marc Anton – One of the best experts on this subject based on the ideXlab platform.
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Structure modification in hen egg yolk low density lipoproteins layers between 30 and 45 mN/m observed by AFM.
Colloids and Surfaces B: Biointerfaces, 2007Co-Authors: Stéphanie Dauphas, Valérie Beaumal, Paul Gunning, Alan Mackie, Peter Wilde, Véronique Vie, Alain Riaublanc, Marc AntonAbstract:We have studied the structure of films made by low density lipoproteins (LDL) from hen egg yolk, which are composed of Apoproteins, neutral lipids and phospholipids. These LDL have been deposited on air-water interface to form a monolayer which has been compressed to measure an isotherm using Langmuir balance. This isotherm presented three transitions (neutral lipid (surface pressure, pi=19 mN/m), apoprotein-lipid (pi=41 mN/m) and phospholipid (pi=51 mN/m) transitions). We have studied only the apoprotein-lipid transition. In order to observe the LDL film structure before (pi=30 mN/m) and after (pi=45 mN/m) the apoprotein-lipid transition, the formed films were transferred and visualised by atomic force microscopy (AFM). Our results have shown that the structures observed in the LDL film were different depending on the surface pressure. The Apoproteins and neutral lipids appeared to be miscible up to the apoprotein-lipid transition, when demixing occurred. The structures observed after the apoprotein-lipid transition should be due to the demixing between Apoproteins and neutral lipids. On the other hand, Apoproteins and phospholipids seemed miscible whatever the surface pressure. Hence, the first transition (pi=19 mN/m) should be attributed to the free neutral lipid collapse; the second transition (pi=41 mN/m) should be attributed to the demixing of apoprotein-neutral lipid complexes; and the last transition (pi=51 mN/m) should be attributed to phospholipid collapse or to demixing of apoprotein-phospholipid complexes.
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chemical and structural characterisation of low density lipoproteins purified from hen egg yolk
Food Chemistry, 2003Co-Authors: Marc Anton, Valérie Beaumal, Virginie Martinet, Michele Dalgalarrondo, Elisabeth Davidbriand, Hanitra RabesonaAbstract:Abstract Low-density lipoproteins (LDL) are considered to be the main contributors to the exceptional emulsifying activity of hen egg yolk. However, the lack of understanding of the molecular basis for LDL functionality is a significant obstacle for good control of yolk emulsions. Consequently, we have attempted to link the structure and the characteristics of LDL with their emulsifying properties. After purification of LDL, we have determined their protein and lipid compositions, their ultrastructure, and then extracted their Apoproteins for physicochemical characterisation. LDL are composed of about 12% of proteins and 87% of lipids and present a spherical shape with a mean diameter of about 35 nm. LDL solubility is high, whatever the medium conditions, because of their low density. LDL contain five major Apoproteins out of which the apoprotein of 15 kDa is considered to be the most surface-active. After extraction, this apoprotein showed a high proportion of amphipathic α-helix chains, explaining the high capacity of this apoprotein to adsorb at the oil–water interface.
Detao Gao – One of the best experts on this subject based on the ideXlab platform.
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cross linking modifications of hdl Apoproteins by oxidized phospholipids structural characterization in vivo detection and functional implications
Journal of Biological Chemistry, 2020Co-Authors: Detao Gao, Mohammad Z Ashraf, Lifang Zhang, Niladri Kar, Tatiana V Byzova, Eugene A PodrezAbstract:Apolipoprotein A-I (apoA-I) is cross-linked and dysfunctional in human atheroma. Although multiple mechanisms of apoA-I cross-linking have been demonstrated in vitro, the in vivo mechanisms of cross-linking are not well-established. We have recently demonstrated the highly selective and efficient modification of high-density lipoprotein (HDL) Apoproteins by endogenous oxidized phospholipids (oxPLs), including γ-ketoalkenal phospholipids. In the current study, we report that γ-ketoalkenal phospholipids effectively cross-link Apoproteins in HDL. We further demonstrate that cross-linking impairs the cholesterol efflux mediated by apoA-I or HDL3 in vitro and in vivo Using LC-MS/MS analysis, we analyzed the pattern of apoprotein cross-linking in isolated human HDL either by synthetic γ-ketoalkenal phospholipids or by oxPLs generated during HDL oxidation in plasma by the physiologically relevant MPO-H2O2-NO2- system. We found that five histidine residues in helices 5-8 of apoA-I are preferably cross-linked by oxPLs, forming stable pyrrole adducts with lysine residues in the helices 3-4 of another apoA-I or in the central domain of apoA-II. We also identified cross-links of apoA-I and apoA-II with two minor HDL Apoproteins, apoA-IV and apoE. We detected a similar pattern of apoprotein cross-linking in oxidized murine HDL. We further detected oxPL cross-link adducts of HDL Apoproteins in plasma and aorta of hyperlipidemic LDLR-/- mice, including cross-link adducts of apoA-I His-165-apoA-I Lys-93, apoA-I His-154-apoA-I Lys-105, apoA-I His-154-apoA-IV Lys-149, and apoA-II Lys-30-apoE His-227. These findings suggest an important mechanism that contributes to the loss of HDL’s atheroprotective function in vivo.
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characterization of covalent modifications of hdl Apoproteins by endogenous oxidized phospholipids
Free Radical Biology and Medicine, 2017Co-Authors: Detao Gao, Eugene A PodrezAbstract:Abstract High density lipoprotein (HDL) is cardioprotective, unless it is pathologically modified under oxidative stress. Covalent modifications of lipid-free apoA-I, the most abundant apoprotein in HDL, compromise its atheroprotective functions. HDL is enriched in oxidized phospholipids (oxPL) in vivo in oxidative stress. Furthermore, oxidized phospholipids can covalently modify HDL Apoproteins. We have now carried out a systematic analysis of modifications of HDL Apoproteins by endogenous oxPL. Human HDL or plasma were oxidized using a physiologically relevant MPO−H2O2−NO2− system or AIPH, or were exposed to synthetic oxPL. Protein adduction by oxPL was assessed using LC-MS/MS and MALDI-TOF MS. The pattern of HDL apoprotein modification by oxPL was independent of the oxidation systems used. ApoA-I and apoA-II were the major modification targets. OxPL with a γ-hydroxy (or oxo)-alkenal were mostly responsible for modifications, and the Michael adduct was the most abundant adduct. Histidines and lysines in helices 5–8 of apoA-I were highly susceptible to oxPL modifications, while lysines in helices 1, 2, 4 and 10 were resistant to modification by oxPL. In plasma exposed to oxidation or synthetic oxPL, oxPL modification was highly selective, and four histidines (H155, H162, H193 and H199) in helices 6–8 of apoA-I were the main modification target. H710 and H3613 in apoB-100 of LDL and K190 of human serum albumin were also modified by oxPL but to a lesser extent. Comparison of oxPL with short chain aldehyde HNE using MALDI-TOF MS demonstrated high selectivity and efficiency of oxPL in the modification of HDL Apoproteins. These findings provide a novel insight into a potential mechanism of the loss of atheroprotective function of HDL in conditions of oxidative stress.