Resveratrol attenuates oxidized LDL-evoked Lox-1 signaling and consequently protects against apoptotic insults to cerebrovascular endothelial cells

被引：58

作者：

Chang, Huai-Chia ^{[1
,2
]}

Chen, Tyng-Guey ^{[3
]}

Tai, Yu-Ting ^{[3
]}

Chen, Ta-Liang ^{[2
]}

Chiu, Wen-Ta ^{[4
,5
]}

Chen, Ruei-Ming ^{[1
,3
,6
]}

机构：

[1] Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei 110, Taiwan

[2] Taipei Med Univ Hosp, Dept Anesthesiol, Taipei, Taiwan

[3] Taipei Med Univ, Wan Fang Med Ctr, Dept Anesthesiol, Taipei 110, Taiwan

[4] Taipei Med Univ, Ctr Excellence Canc Res, Taipei 110, Taiwan

[5] Taipei Med Univ, Ctr Excellence Clin Trial & Res Neurosci, Taipei 110, Taiwan

[6] Taipei Med Univ, Wan Fang Med Ctr, Cell Physiol & Mol Image Res Ctr, Taipei 110, Taiwan

来源：

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2011年 / 31卷 / 03期

关键词：

antiapoptotic events; cerebrovascular endothelial cells; Lox-1; oxidized low-density lipoprotein; resveratrol; LOW-DENSITY-LIPOPROTEIN; CASPASE PROTEASE PATHWAY; BLOOD-BRAIN-BARRIER; N-TERMINAL KINASE; OXIDATIVE STRESS; NITRIC-OXIDE; HUMAN CHONDROCYTES; GENE-EXPRESSION; KAPPA-B; C-JUN;

D O I：

10.1038/jcbfm.2010.180

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (benzyloxy-carbonyl-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. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 842-854; doi:10.1038/jcbfm.2010.180; published online 13 October 2010

引用

页码：842 / 854

页数：13

共 46 条

[1] Astrocyte-endothelial interactions and blood-brain barrier permeability [J].

Abbott, NJ .

JOURNAL OF ANATOMY, 2002, 200 (06) :629-638

[2] Effects of preconditioning on tight junction and cell adhesion of cerebral endothelial cells [J].

An, Ping ;

Xue, Yi-Xue .

BRAIN RESEARCH, 2009, 1272 :81-88

[3] Multiple molecular targets of resveratrol: Anti-carcinogenic mechanisms [J].

Athar, Mohammad ;

Back, Jung Ho ;

Kopelovich, Levy ;

Bickers, David R. ;

Kim, Arianna L. .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2009, 486 (02) :95-102

[4] Therapeutic potential of resveratrol:: the in vivo evidence [J].

Baur, Joseph A. ;

Sinclair, David A. .

NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (06) :493-506

[5]

Betz AL, 1996, ADV NEUROL, V71, P301

[6] Nitric oxide protects osteoblasts from oxidative stress-induced apoptotic insults via a mitochondria-dependent mechanism [J].

Chang, Chia-Chen ;

Liao, Yi-Shyan ;

Lin, Yi-Ling ;

Chen, Ruei-Ming .

JOURNAL OF ORTHOPAEDIC RESEARCH, 2006, 24 (10) :1917-1925

[7]

Chang HC, 2010, SHOCK, V33, P485, DOI 10.1097/SHK.0b013e3181c3cea5

[8] Ketamine reduces nitric oxide biosynthesis in human umbilical vein endothelial cells by down-regulating endothelial nitric oxide synthase expression and intracellular calcium levels [J].

Chen, RM ;

Chen, TL ;

Lin, YL ;

Chen, TG ;

Tai, YT .

CRITICAL CARE MEDICINE, 2005, 33 (05) :1044-1049

[9] Nitric oxide induces osteoblast apoptosis through the de novo synthesis of Bax protein [J].

Chen, RM ;

Liu, HC ;

Lin, YL ;

Jean, WC ;

Chen, JS ;

Wang, JH .

JOURNAL OF ORTHOPAEDIC RESEARCH, 2002, 20 (02) :295-302

[10] Signal-transducing mechanisms of ketamine-caused inhibition of interleukin-1β gene expression in lipopolysaccharide-stimulated murine macrophage-like Raw 264.7 cells [J].

Chen, Ta-Liang ;

Chang, Chia-Chen ;

Lin, Yi-Ling ;

Ueng, Yune-Fang ;

Chen, Ruei-Ming .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 2009, 240 (01) :15-25

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