title: N-homocysteinylation of apolipoprotein A-I impairs the protein's antioxidant ability but not its cholesterol efflux capacity.
abstract: A high homocysteine (Hcy) level is a risk factor for atherosclerosis. Hcy can be added to proteins through a process known as N-homocysteinylation. This is thought to be a potential cause of atherosclerosis induction. We previously reported that N-homocysteinylated apolipoprotein A-I (N-Hcy-apoA-I) was identified in normal human plasma. In this study, the effect of N-homocysteinylation on the functions of apoA-I was examined. A kinetic study using dimyristoyl phosphatidylcholine (DMPC) liposomes indicated that N-Hcy-apoA-I showed increased lipid-binding activity compared to wild-type apoA-I. Two reconstituted high-density lipoprotein (rHDL) particles of different sizes (approximately 8.2 nm and 7.6 nm in diameter) were produced by mixing apoA-I and 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC). However, an increased ratio of large to small particles was found in rHDL prepared with N-Hcy-apoA-I. The normal apoA-I antioxidant ability, estimated by the suppression of conjugated diene formation in low-density lipoprotein (LDL) induced by copper sulfate oxidation, was considerably impaired when using N-Hcy-apoA-I. Although N-Hcy-apoA-I functioned as an oxidant, no significant difference was observed in the cholesterol efflux capacity from THP-1 macrophages between wild-type apoA-I and N-Hcy-apoA-I. These results suggest that N-Hcy-apoA-I might be proatherogenic due to its oxidative behavior but not an attenuation of cholesterol efflux capacity.
authors: Akari
authors: A
authors: Miyazaki
authors: Nozomi
authors: N
authors: Sagae
authors: Yoko
authors: Y
authors: Usami
authors: Megumi
authors: M
authors: Sato
authors: Takahiro
authors: T
authors: Kameda
authors: Akira
authors: A
authors: Yoshimoto
authors: Nau
authors: N
authors: Ishimine
authors: Kazuyuki
authors: K
authors: Matsuda
authors: Mitsutoshi
authors: M
authors: Sugano
authors: Masayuki
authors: M
authors: Hara
authors: Takayuki
authors: T
authors: Honda
authors: Minoru
authors: M
authors: Tozuka
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D016632:Apolipoprotein A-I; D002784:Cholesterol