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. METHODS AND 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.
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. METHODS AND 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 humanatherosclerotic lesions. CONCLUSIONS:PC-HAs are present in vivo and possess multiple functions characteristic of oxidized LDL and 4-hydroxynonenal.
Authors: Mohammad Z Ashraf; Niladri S Kar; Xi Chen; Jaewoo Choi; Robert G Salomon; Maria Febbraio; Eugene A Podrez Journal: J Biol Chem Date: 2008-02-19 Impact factor: 5.157
Authors: Olga V Oskolkova; Taras Afonyushkin; Alexander Leitner; Elena von Schlieffen; Peter S Gargalovic; Aldons J Lusis; Bernd R Binder; Valery N Bochkov Journal: Blood Date: 2008-05-01 Impact factor: 22.113
Authors: Amir Ravandi; Saeid Babaei; Ramsey Leung; Juan Carlos Monge; George Hoppe; Henry Hoff; Hiroshi Kamido; Arnis Kuksis Journal: Lipids Date: 2004-02 Impact factor: 1.880