Phospholipid hydroxyalkenals: biological and chemical properties of specific oxidized lipids present in atherosclerotic lesions.
OBJECTIVE
Phosphatidylcholine hydroxyalkenals (PC-HAs) are a class of oxidized PCs derived from lipid peroxidation of arachidonate or linoleate at the sn-2 position to form terminal gamma-hydroxy, alpha-, and beta-unsaturated aldehydes. The aim of this study was to characterize some of their biological properties, ascertain the mechanism of their action, and assess whether they have in vivo relevance.


RESULTS
Combinations of cell biological approaches with radiolabels, mass spectroscopy, and immunochemical as well as immunohistochemical techniques were used to show that PC-HAs reduce the proteolytic degradation by mouse peritoneal macrophages (MPMs) of internalized macromolecules, such as maleylated bovine serum albumin, and that the activity of the lysosomal protease, cathepsin B, in MPMs form Michael adducts with MPM proteins and with N-acetylated cysteine in vitro form pyrrole adducts with MPM proteins and reduce the maturation of Rab5a, thereby impairing phagosome-lysosome fusion (maturation) in phagocytes; they are present unbound and as pyrrole adducts in human atherosclerotic lesions.


CONCLUSIONS
PC-HAs are present in vivo and possess multiple functions characteristic of oxidized LDL and 4-hydroxynonenal.
Hoff
Henry F
HF
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA. hoffh@ccf.org
O'Neil
June
J
Wu
Zhiping
Z
Hoppe
George
G
Salomon
Robert L
RL
D000111:Acetylcysteine / Q000737:chemistry / Q000378:metabolism; D000447:Aldehydes / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology*; D001692:Biological Transport; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D002788:Cholesterol Esters / Q000737:chemistry / Q000378:metabolism; D002853:Chromatography, Liquid; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000276:immunology; D008247:Lysosomes / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry / Q000276:immunology; D021241:Spectrometry, Mass, Electrospray Ionization
D000447:Aldehydes; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D010743:Phospholipids; D011758:Pyrroles; C099252:oxidized low density lipoprotein; D002401:Cathepsin B; C027576:4-hydroxy-2-nonenal; D008239:Lysine; D000111:Acetylcysteine