ABSTRACT
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.
Subject(s)
ATP-Binding Cassette Transporters/biosynthesis , Apoptosis , Cell Membrane/chemistry , Endothelial Cells/drug effects , Shiga Toxin/toxicity , Trihexosylceramides/metabolism , ATP Binding Cassette Transporter 1 , ATP-Binding Cassette Transporters/antagonists & inhibitors , Apolipoprotein A-I/metabolism , Cells, Cultured , Cholesterol/metabolism , Endothelial Cells/metabolism , Gene Knockdown Techniques , Humans , Membrane Microdomains/metabolism , Phosphodiesterase Inhibitors/pharmacology , RNA, Small Interfering/metabolism , Rolipram/pharmacology , Shiga Toxin/metabolismABSTRACT
We have experienced a case of total laryngectomy with graft of the rectus abdominis muscle skin flap because of the recurrent lingual cancer. Just before the operation, we used right basilic vein for introduction of a central venous catheter. Right shoulder pain occurred on the first postoperative day. After the operation, we found that the catheter from the right basilic vein was inserted to the right jugular vein. We pulled out it and inserted another catheter from the left subclavian vein. Shoulder pain diminished and then pyrexia and symptom of infection diminished. After recatheterization, shoulder pain was suspected to be the result of frozen shoulder. We should be aware that shoulder pain could occur by immobility of upper extremities when basilic venous catheter is in place.
