Revealing binding sites for myeloperoxidase on the surface of human low density lipoproteins

Sokolov, A. V.; Чеканов, А. В.; Kostevich, Valeria A.; Aksenov, D. V.; Vasilyev, V. B.; Панасенко, О. М.

doi:10.1016/j.chemphyslip.2010.10.004

Cited by 18 publications

(12 citation statements)

References 25 publications

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“…The remaining sidechains (on N355, N391, and N729) decorate the exposed surface of the heavy subunit of mature dimeric MPO with six carbohydrate groups that are accessible and available to bind to surfaces and thus target MPO-dependent oxidants more precisely. The oligosaccharides on MPO have been implicated in neutrophil activation via engagement of β2 integrins [55] as well as in binding to microbes [56], macrophages [57–60], extracellular matrix [61], and lipids [62]. In the context of MPO and innate immunity against infection [63], glycosylation of MPO may benefit host defense.…”

Section: Events In the Endoplasmic Reticulummentioning

confidence: 99%

Biosynthesis of human myeloperoxidase

Nauseef

2018

Archives of Biochemistry and Biophysics

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Members of Chordata peroxidase subfamily [1] expressed in mammals, including myeloperoxidase (MPO), eosinophil peroxidase (EPO), lactoperoxidase (LPO), and thyroid peroxidase (TPO), express conserved motifs around the heme prosthetic group essential for their activity, a calcium-binding site, and at least two covalent bonds linking the heme group to the protein backbone. Although most studies of the biosynthesis of these peroxidases have focused on MPO, many of the features described occur during biosynthesis of other members of the protein subfamily. Whereas MPO biosynthesis includes events typical for proteins generated in the secretory pathway, the importance and consequences of heme insertion are events uniquely associated with peroxidases. This Review summarizes decades of work elucidating specific steps in the biosynthetic pathway of human MPO. Discussion includes cotranslational glycosylation and subsequent modifications of the N-linked carbohydrate sidechains, contributions by molecular chaperones in the endoplasmic reticulum, cleavage of the propeptide from proMPO, and proteolytic processing of protomers and dimerization to yield mature MPO. Parallels between the biosynthesis of MPO and TPO as well as the impact of inherited mutations in the MPO gene on normal biosynthesis will be summarized. Lastly, specific gaps in our knowledge revealed by this review of our current understanding will be highlighted.

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Section: Events In the Endoplasmic Reticulummentioning

confidence: 99%

Biosynthesis of human myeloperoxidase

Nauseef

2018

Archives of Biochemistry and Biophysics

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“…They also demonstrated that ceruloplasmin, which is a human plasmatic protein and a physiological MPO inhibitor [96], is able to inhibit MPO activity when HDL is present but not in the presence of LDL. The same group then studied the binding site for MPO on apoB-100 [97]. The authors predicted that MPO should bind to the NH 2 - βα 1 domain of apoB-100 because this domain is exposed on the outside of the lipoprotein.…”

Section: Modification Of Ldl Myeloperoxidase and Mox-ldlmentioning

confidence: 99%

Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

Delporte

Antwerpen

Vanhamme

et al. 2013

Mediators of Inflammation

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Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNFα and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis.

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“…MPO is a highly cationic protein that is able to bind to endothelial cells, leukocytes and LDL ( 2 ). Sokolov et al ( 8 ) concluded that the likely site of interaction with MPO is the amino acid stretch 445–456 of apoB-100 though mimicking 3 kinds of apoB-100 fragments. Numerous studies have suggested that MPO adsorbs onto the surface of LDL, promoting the oxidation of amino acid residues and the formation of oxidized lipoproteins ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Native low density lipoprotein promotes lipid raft formation in macrophages

Jiang

Ping

Duong

et al. 2016

Molecular Medicine Reports

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Oxidized low-density lipoprotein (LDL) has an important role in atherogenesis; however, the mechanisms underlying cell-mediated LDL oxidation remain to be elucidated. The present study investigated whether native-LDL induced lipid raft formation, in order to gain further insight into LDL oxidation. Confocal microscopic analysis revealed that lipid rafts were aggregated or clustered in the membrane, which were colocalized with myeloperoxidase (MPO) upon native LDL stimulation; however, in the presence of methyl-β-cyclodextrin (MβCD), LDL-stimulated aggregation, translocation, and colocalization of lipid rafts components was abolished.. In addition, lipid raft disruptors MβCD and filipin decreased malondialdehyde expression levels. Density gradient centrifugation coupled to label-free quantitative proteomic analysis identified 1,449 individual proteins, of which 203 were significantly upregulated following native-LDL stimulation. Functional classification of the proteins identified in the lipid rafts revealed that the expression levels of translocation proteins were upregulated. In conclusion, the results of the present study indicated that native-LDL induced lipid raft clustering in macrophages, and the expression levels of several proteins were altered in the stimulated macrophages, which provided novel insights into the mechanism underlying LDL oxidation.

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Revealing binding sites for myeloperoxidase on the surface of human low density lipoproteins

Cited by 18 publications

References 25 publications

Biosynthesis of human myeloperoxidase

Biosynthesis of human myeloperoxidase

Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

Native low density lipoprotein promotes lipid raft formation in macrophages

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