The Endothelium-Derived Hyperpolarizing Factor, H2O2, Promotes Metal-Ion Efflux in Aortic Endothelial Cells: Elemental Mapping by a Hard X-ray Microprobe

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• 作者：Paul K. Witting ; Hugh H. Harris ; Benjamin S. Rayner ; Jade B. Aitken ; Carolyn T. Dillon ; Roland Stocker ; Barry Lai ; Zhonghou Cai ; Peter A. Lay
• 刊名：Biochemistry
• 出版年：2006
• 出版时间：October 17, 2006
• 年：2006
• 卷：45
• 期：41
• 页码：12500 - 12509
• 全文大小：214K
• 年卷期：v.45,no.41(October 17, 2006)
• ISSN：1520-4995

文摘

Hydrogen peroxide (H₂O₂) is a physiologic oxidant implicated in vascular cell signaling,although little is known about the biochemical consequences of its reaction with endothelial cells.Submicrometer-resolution hard X-ray elemental mapping of cultured porcine aortic endothelial cells (PAEC)has provided data on the global changes for intracellular elemental density within PAEC and indicates anefflux of metal ions and phosphorus from the cytoplasm after H₂O₂ treatment. The synchrotron-radiation-induced X-ray emission experiments (SRIXE) show that H₂O₂-treated cells are irregularly shaped andexhibit blebbing indicative of increased permeability due to the damaged membrane. The SRIXE resultssuggest that H₂O₂-induced damage is largely restricted to the cell membrane as judged by the changes tomembrane and cytoplasmic components rather than the cell nucleus. The SRIXE data also provide amechanism for cell detoxification as the metal-ion efflux resulting from the initial H₂O₂-mediated changesto cell membrane potentially limits intracellular metal-mediated redox processes through Fenton-likechemistry. They may also explain the increased levels of these ions in atherosclerotic plaques, regardlessof whether they are involved in plaque formation. Finally, the SRIXE data support the notion that culturedendothelial cells exposed to H₂O₂ respond with enhanced cellular metal-ion efflux into the extracellularspace.