アラシキ　ノブト   ARASHIKI Nobuto   新敷　信人    所属   医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The covalent modification of spectrin in red cell membranes by the lipid peroxidation product 4-hydroxy-2-nonenal.
掲載誌名	正式名：Biochemical and biophysical research communications 略　 称：Biochem Biophys Res Commun ISSNコード：(1090-2104)0006-291X(Linking)
掲載区分	国外
巻・号・頁	391(3),pp.1543-7
著者・共著者	Arashiki Nobuto, Otsuka Yayoi, Ito Daisuke, Yang Mira, Komatsu Tomohiko, Sato Kota, Inaba Mutsumi
担当区分	筆頭著者
発行年月	2010/01
概要	Spectrin strengthens the red cell membrane through its direct association with membrane lipids and through protein-protein interactions. Spectrin loss reduces the membrane stability and results in various types of hereditary spherocytosis. However, less is known about acquired spectrin damage. Here, we showed that alpha- and beta-spectrin in human red cells are the primary targets of the lipid peroxidation product 4-hydroxy-2-nonenal (HNE) by immunoblotting and mass spectrometry analyses. The level of HNE adducts in spectrin (particularly alpha-spectrin) and several other membrane proteins was increased following the HNE treatment of red cell membrane ghosts prepared in the absence of MgATP. In contrast, ghost preparation in the presence of MgATP reduced HNE adduct formation, with preferential beta-spectrin modification and increased cross-linking of the HNE-modified spectrins. Exposure of intact red cells to HNE resulted in selective HNE-spectrin adduct formation with a similar preponderance of HNE-beta-spectrin modifications. These findings indicate that HNE adduction occurs preferentially in spectrin at the interface between the skeletal proteins and lipid bilayer in red cells and suggest that HNE-spectrin adduct aggregation results in the extrusion of damaged spectrin and membrane lipids under physiological and disease conditions.
DOI	10.1016/j.bbrc.2009.12.121
PMID	20036642