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  • Title: Proteolysis and fusion of low density lipoprotein particles independently strengthen their binding to exocytosed mast cell granules.
    Author: Paananen K, Kovanen PT.
    Journal: J Biol Chem; 1994 Jan 21; 269(3):2023-31. PubMed ID: 8294453.
    Abstract:
    Contact between low density lipoproteins (LDL) and exocytosed mast cell granules, the "granule remnants," leads to binding of LDL to the granule remnants via ionic interactions between the apolipoprotein B-100 (apoB-100) component of LDL and the heparin proteoglycan component of the granule remnants. Upon incubation at 37 degrees C, the heparin proteoglycan-bound apoB-100 is progressively proteolyzed by remnant chymase and carboxypeptidase A, which are also bound to the heparin proteoglycans. Thereupon, the LDL particles fuse, and their binding to the granule remnants strengthens, as defined by the decreased ability of NaCl to release LDL from the remnants. We now have examined separately the effects of proteolysis and fusion on LDL binding. Proteolysis without fusion was induced by lowering the incubation temperature to 15 degrees C, and proteolysis-independent fusion was induced by treating granule remnant-bound LDL with sphingomyelinase in the presence of protease inhibitors. It was found that degradation of the heparin proteoglycan-bound apoB-100, even without accompanying particle fusion, increased the strength of LDL binding to the granule remnants, suggesting exposure of buried heparin binding regions of apoB-100. When such proteolyzed LDL particles were allowed to fuse, the strength of their binding to the granule remnants increased still further, probably because of an increase in the number of apoB-100 fragments in the enlarged particles. Proteolysis-independent fusion, induced by sphingomyelinase treatment of granule remnant-bound LDL, also increased the strength of binding. The results show that proteolytic degradation and fusion, the two modifications of granule remnant-bound LDL subsequent to action by chymase and carboxypeptidase A of the granule remnants, represent two separate mechanisms by which LDL particles become tightly bound to the heparin proteoglycans of exocytosed mast cell granules. Since the formation of an atheroma, the hallmark of atherosclerosis, is characterized by accumulation in the proteoglycan matrix of the arterial intima of extracellular lipid droplets resembling the fused LDL particles on the granule remnant surfaces, the modifications of LDL described in this study may provide a clue to the actual processes by which the lipid droplets are anchored to the arterial intima.
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