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SHR Neuro Krebs Kardio Lipid

Rees, MD; Whitelock, JM; Malle, E; Chuang, CY; Iozzo, RV; Nilasaroya, A; Davies, MJ.
Myeloperoxidase-derived oxidants selectively disrupt the protein core of the heparan sulfate proteoglycan perlecan.
Matrix Biol. 2010; 29(1): 63-73. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Malle Ernst
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Number of Figures: 7
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Abstract:
The potent oxidants hypochlorous acid (HOCl) and hypobromous acid (HOBr) are produced extracellularly by myeloperoxidase, following release of this enzyme from activated leukocytes. The subendothelial extracellular matrix is a key site for deposition of myeloperoxidase and damage by myeloperoxidase-derived oxidants, with this damage implicated in the impairment of vascular cell function during acute inflammatory responses and chronic inflammatory diseases such as atherosclerosis. The heparan sulfate proteoglycan perlecan, a key component of the subendothelial extracellular matrix, regulates important cellular processes and is a potential target for HOCl and HOBr. It is shown here that perlecan binds myeloperoxidase via its heparan sulfate side chains and that this enhances oxidative damage by myeloperoxidase-derived HOCl and HOBr. This damage involved selective degradation of the perlecan protein core without detectable alteration of its heparan sulfate side chains, despite the presence of reactive GlcNH(2) residing within this glycosaminoglycan. Modification of the protein core by HOCl and HOBr (measured by loss of immunological recognition of native protein epitopes and the appearance of oxidatively-modified protein epitopes) was associated with an impairment of its ability to support endothelial cell adhesion, with this observed at a pathologically-achievable oxidant dose of 425nmol oxidant/mg protein. In contrast, the heparan sulfate chains of HOCl/HOBr-modified perlecan retained their ability to bind FGF-2 and collagen V and were able to promote FGF-2-dependent cellular proliferation. Collectively, these data highlight the potential role of perlecan oxidation, and consequent deregulation of cell function, in vascular injuries by myeloperoxidase-derived HOCl and HOBr.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Bromates - metabolism
Cell Adhesion - physiology
Cells, Cultured -
Collagen Type V - metabolism
Endothelial Cells - cytology
Epitopes - chemistry
Fibroblast Growth Factor 2 - metabolism
Glycosaminoglycans - metabolism
Heparan Sulfate Proteoglycans - chemistry
Humans -
Hypochlorous Acid - metabolism
Oxidants - metabolism
Oxidation-Reduction -
Peroxidase - metabolism
Protein Binding -

Find related publications in this database (Keywords)
Oxidation
Heparan sulfate
Perlecan
Myeloperoxidase
Inflammation
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