Document Detail


Resveratrol attenuates oxidized LDL-evoked Lox-1 signaling and consequently protects against apoptotic insults to cerebrovascular endothelial cells.
MedLine Citation:
PMID:  20940732     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Huai-Chia Chang; Tyng-Guey Chen; Yu-Ting Tai; Ta-Liang Chen; Wen-Ta Chiu; Ruei-Ming Chen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-13
Journal Detail:
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:
Created Date:  2011-03-01     Completed Date:  2011-04-27     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  842-54     Citation Subset:  IM    
Affiliation:
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
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:
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; 9007-43-6/Cytochromes c; EC 3.4.-/Peptide Hydrolases; EC 3.4.22.-/Caspases; Q369O8926L/resveratrol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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