Enhanced expression of ATP-binding cassette transporter A1 in non-rafts decreases the sensitivity of vascular endothelial cells to Shiga toxin.

Shiga toxin (Stx) binds to globotriaosyl ceramide (Gb3) receptors on the surface of vascular endothelial cells, which is followed by Gb3-dependent endocytosis, and initiates a cascade leading to cell damage. The Gb3 receptor is localized in lipid rafts, in which cholesterol is tightly packed primarily with sphingolipids in a liquid-ordered state. Recent studies have indicated that phosphodiesterase (PDE) type 4 inhibitors enhance the expression of ATP-binding cassette 1 (ABCA1) which promotes cholesterol efflux from non-rafts at the plasma membrane. Here we report that rolipram, a PDE4 inhibitor, reduced the sensitivity to Stx2 of human umbilical vascular endothelial cells in association with increased apolipoproteinA-I (apoA-I)-mediated cholesterol efflux, and shift of some Gb3 molecules from lipid rafts into non-rafts. Although rolipram treatment did not reduce Gb3 content at the plasma membrane and Stx binding to whole cells of HUVECs, it reduced Stx2 endocytosis. Knockdown of ABCA1 by transfection with siRNA ABCA1 in vascular endothelial cells abrogated the protective effect of rolipram on Stx2-exposed cells. Our present results suggest that the expression level of ABCA1 protein is one of critical determinants of Stx sensitivity levels in vascular endothelial cells.;博士(医学)・乙1324号・平成26年3月17日;開始ページ : 141;終了ページ : 152;PubMed番号 : http://www.ncbi.nlm.nih.gov/pubmed/20553836

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書名 Enhanced expression of ATP-binding cassette transporter A1 in non-rafts decreases the sensitivity of vascular endothelial cells to Shiga toxin.
著作者等 Kasahara, Kazuki
Kita, Eiji
Matsumura, Youko
Mikasa, Keiichi
Mizuno, Fumiko
Sugiura, Shigeki
Higashi, Nobutaka
書名別名 非ラフト部分のATP結合カセット輸送体A1の発現増強は、血管内皮細胞の志賀毒素に対する感受性を減少させる
出版元 Academic Press/Elsevier
ISSN 08824010
NCID AA10609161
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言語 英語
出版国 イギリス
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