Susceptibility of phospholipids of oxidizing LDL to enzymatic hydrolysis modulates uptake by P388D1 macrophage-like cells.
Addition of the phospholipids 1-O-hexadecyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PLE) and 1-O-hexa-decyl-2-desoxy-2-amino-arachidonyl-sn-glycero-3- phosphocholine (PLA) to [125I]LDL and subsequent Cu(2+)-induced oxidation result in significant differences in protein modification and uptake by P388D1 macrophage-like cells. PLE-treated LDL is ingested at a 1.27-fold rate compared to PLE-treated LDL and displays enhanced electrophilic mobility. Similar results (1.43-fold enhanced uptake of LDL preloaded with PLE) are obtained when the uptake of phospholipid-enriched oxLDL particles are examined. The preference for ingestion as well as protein modification of both preparations is, however, reversed under experimental conditions allowing diffusion and inactivation of a fraction of the peroxidation products. These findings suggest that LDL-associated PAF-acetylhydrolase can exert a dual role and, to be protective to LDL, require an appropriate microenvironment, capable of binding certain species of oxidatively fragmented lipids.
Fyrnys
B
B
Pharmazeutisch-Chemisches Institut, Universität Heidelberg, Germany.
Blencowe
C
C
Deigner
H P
HP
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D002460:Cell Line; D006801:Humans; D006868:Hydrolysis; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D010084:Oxidation-Reduction; D010741:Phospholipases A / Q000378:metabolism*; D010742:Phospholipid Ethers / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism
C091046:1-O-hexadecyl-2-desoxy-2-aminoarachidonoylglycero-3-phosphocholine; D008077:Lipoproteins, LDL; D010742:Phospholipid Ethers; D010743:Phospholipids; D010972:Platelet Activating Factor; C043051:1-O-hexadecyl-2-arachidonyl-sn-glycero-3-phosphocholine; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase