| Resveratrol attenuates oxidized LDL-evoked Lox-1 signaling and consequently protects against apoptotic insults to cerebrovascular endothelial cells. | |
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MedLine Citation:
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PMID: 20940732 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cerebrovascular endothelial cells (CECs) are crucial components of the blood-brain barrier. Our previous study showed that oxidized low-density lipoprotein (oxLDL) induces apoptosis of CECs. This study was designed to further evaluate the effects of resveratrol on oxLDL-induced CEC insults and its possible molecular mechanisms. Resveratrol decreased the oxidation of LDL into oxLDL. Additionally, the oxLDL-caused oxidative stress and cell damage were attenuated by resveratrol. Exposure of CECs to oxLDL induced cell shrinkage, DNA fragmentation, and cell apoptosis, but resveratrol defended against such injuries. Application of Lox-1 small interference (si)RNA into CECs reduced the translation of this membrane receptor, and simultaneously increased resveratrol protection from oxLDL-induced cell apoptosis. By comparison, overexpression of Lox-1 attenuated resveratrol protection. Resveratrol inhibited oxLDL-induced Lox-1 mRNA and protein expressions. Both resveratrol and Lox-1 siRNA decreased oxLDL-enhanced translocation of proapoptotic Bcl-2-associated X protein (Bax) from the cytoplasm to mitochondria. Sequentially, oxLDL-induced alterations in the mitochondrial membrane potential, cytochrome c release, and activities of caspases-9, -3, and -6 were decreased by resveratrol. Pretreatment with Z-VEID-FMK (benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethyl ketone) synergistically promoted resveratrol's protection against DNA fragmentation and cell apoptosis. Therefore, this study shows that resveratrol can protect CECs from oxLDL-induced apoptotic insults via downregulating Lox-1-mediated activation of the Bax-mitochondria-cytochrome c-caspase protease pathway. |
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Authors:
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Huai-Chia Chang; Tyng-Guey Chen; Yu-Ting Tai; Ta-Liang Chen; Wen-Ta Chiu; Ruei-Ming Chen |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-13 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 31 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-01 Completed Date: 2011-04-27 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 842-54 Citation Subset: IM |
Affiliation:
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Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / pharmacology* Apoptosis / drug effects* Caspases / metabolism Cell Survival / drug effects Cells, Cultured Cerebrovascular Circulation* Cytochromes c / metabolism Cytoprotection Down-Regulation Endothelial Cells / drug effects, physiology* Lipoproteins, LDL / antagonists & inhibitors, pharmacology* Membrane Potentials / drug effects Mice Mitochondria / physiology Peptide Hydrolases / metabolism RNA, Messenger / antagonists & inhibitors, drug effects RNA, Small Interfering / pharmacology Reactive Oxygen Species / antagonists & inhibitors Receptors, Cell Surface / metabolism Scavenger Receptors, Class E / antagonists & inhibitors, genetics, metabolism* Signal Transduction / drug effects* Stilbenes / pharmacology* Tissue Distribution / drug effects bcl-2-Associated X Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Lipoproteins, LDL; 0/Olr1 protein, mouse; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Reactive Oxygen Species; 0/Receptors, Cell Surface; 0/Scavenger Receptors, Class E; 0/Stilbenes; 0/bcl-2-Associated X Protein; 0/oxidized low density lipoprotein; 501-36-0/resveratrol; 9007-43-6/Cytochromes c; EC 3.4.-/Peptide Hydrolases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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