Interaction domains of p62: A bridge between p62 and selective autophagy
作者:
Lin, Xiaolong;Li, Shuang;Zhao, Yue;Ma, Xiaofeng;Zhang, Kai;...
期刊:
DNA AND CELL BIOLOGY ,2013年32(5):220-227 ISSN:1044-5498
通讯作者:
Wang, Zuo
作者机构:
[Zhao, Yue; Ma, Xiaofeng; Li, Shuang; He, Xinglan; Wang, Zuo; Zhang, Kai; Lin, Xiaolong] Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.
通讯机构:
[Wang, Zuo] U;Univ South China, Inst Cardiovasc Dis, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.
摘要:
p62 is a multidomain protein that contains different kinds of protein-protein interaction domains, including an N-terminal PB1 domain, a ZZ-type zinc finger domain, a nuclear localization signal (NLS), an export motif (NES), the LC3-interacting region (LIR), the KEAP1-interacting region (KIR), and a C-terminal Ub-associated domain (UBA). p62 is involved in the degradation of protein aggregates and cytoplasmic bodies via selective autophagy through its PB1, LIR, and UBA domains to maintain homeostasis in the cell. Moreover, NES, NLS, KIR, and ZZ domains have been found to be linked to ubiquitinated protein degradation by autophagy. Therefore, understanding the functional domains of p62 is important. In this review, we attempt to expound the mechanism of connection between p62 and selective autophagy to illustrate how the domains of p62 regulate selective autophagy, and to provide a new direction and perspective on selective autophagy research. © Copyright 2013, Mary Ann Liebert, Inc. 2013.
语种:
英文
展开
5-Aza-CR调节FXR基因去甲基化抑制载脂蛋白(a)表达
作者:
谭剑凯;谭小进;赵岳;林小龙;何兴兰;...
期刊:
中国动脉硬化杂志 ,2013年(9):I0039-I0039 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化湖南省重点实验室
关键词:
载脂蛋白(a);DNA甲基化
摘要:
目的观察5-Aza—CR的DNA去甲基化作用对HepG2细胞载脂蛋白(a)[Apo(a)]表达的影响,并探讨其作用机制。方法选取Apo(a)高表达细胞株HepG2细胞为研究对象,MTT法测定不同浓度的5-Aza—CR处理细胞72h后细胞相对存活率,选取合适药物作用浓度范围;通过Westernblot检测5-Aza—CR不同浓度组和不同处理时间组HepG2细胞Apo(a)、FXR的表达水平,用RT—PCR检测Apo(a)、FXR的mRNA水平;MSP检测5-Aza-CR不同浓度组及不同时间组FXR基因启动子甲基化水平。
语种:
中文
展开
胆酸通过FXR/miR-23b-3p/HNF4途径下调载脂蛋白(a)表达
作者:
莫学靓;林小龙;何兴兰;马小峰;张凯;...
期刊:
中国动脉硬化杂志 ,2013年21(9):I0046 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化湖南省重点实验室,湖南省衡阳市421001
会议名称:
第十二次全国动脉硬化性疾病学术会议
会议时间:
2013-10-11
会议地点:
江苏苏州
会议论文集名称:
第十二次全国动脉硬化性疾病学术会议论文集
关键词:
胆酸;载脂蛋白(a);HepG2细胞;靶基因
摘要:
目的 前期研究发现miR-23b-3p高效降HepG2细胞载脂蛋白(a)[Apo(a)]表达,本研究拟在基础上分析胆酸降Apo(a)效用与miR-23b-3P的关系,并检测胆酸调控miR-23b-3p表达的机制,分析miR-23b-3p作用靶基因。研究胆酸降Apo(a)作用新机制。方法 首先用miRanda、Targetscan、PITA三个生物信息学在线工具对miR-23b-3p与调控筛选调控LPA基因的转录因子HNF4进行靶基因分析,然后验证胆酸对高表达Apo(a)细胞株HepG2的降Apo(a)效用的时间(0h、6h、12 h、24 h、48 h)和量效(0、0 5、2、8、32 mg/L)关系,然后分析胆酸抑制Apo (a)表达与MAPK和miR-23b-3p的关系,分析胆酸活化MAPK并上调miR-23b-3p表达作用,分析胆酸调控miR-23b-3p表达与FXR及 MAPK的关系,分析FXR、MAPK结合转录miR-23b-3p的基因启动子情况,最后使用荧光素酶报告系统对miR-23b-3p与调控筛选调控LPA基因的转录因子HNF4进行靶基因验证实验。用Western blot检测Apo(a)表达水平、p38MAPK及p-p38MAPK、实时定量PCR检测miR-23b-3p表达水平。结果 miRanda、Targetscan、PITA三个生物信息学分析工具表明HNF4G可作为miR-23b-3p的靶基因,胆酸呈时间和剂量依赖性调控HepG2细胞Apo(a)的表达,以32 mg/L和24h的作用效果最显著,48 h作用效果下降,胆酸抑制Apo(a)表达与MAPK和miR-23b-3p有关,胆酸能活化MAPK并上调miR-23b-3p表达,胆酸调控miR-23b-3p表达与FXR及MAPK,FXR在转录miR-23b-3p的基因启动子区域有8个结合位点,未发现MAPK的结合位点,MAPK可能通过间接作用于转录miR-23b-3p的基因启动子区域而发挥下调miR-23b-3p作用。使用FXR拮抗剂抑制miR-23b-3p表达的效用要强于抑制MAPK,可能胆酸更多地通过FXR来介导其上调miR-23b-3p效用,而MAPK只是胆酸发挥效用的信号途径的一个分支,转染miR-23b-3p处理组细胞裂解后荧光强度显著低于对照组,验证了HNF4G可作为miR-23b-3p的靶基因。结论 胆酸呈剂量和时间依赖性地下调HepG2细胞Apo(a)表达水平;胆酸降Apo (a)与FXR/miR-23b-3p/HNF4途径有关。
语种:
中文
展开
Apolipoprotein (a) impairs endothelial progenitor cell-mediated angiogenesis
作者:
Wang, Ren;Zhang, Kai;Li, Shuang;Tong, Zhongyi;Li, Guohua;...
期刊:
DNA AND CELL BIOLOGY ,2013年32(5):243-251 ISSN:1044-5498
通讯作者:
Wang, Zuo
作者机构:
[Zhao, Yue; Li, Guohua; Wang, Ren; Li, Shuang; Zhao, Zhanzhi; Jiang, Zhisheng; Wang, Zuo; Liu, Fengtao; Lin, Xiaolong] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang City 421001, Peoples R China.;[Zhang, Kai] Univ South China, Affiliated Hosp 2, ICU Dept, Hengyang City 421001, Peoples R China.;[Tong, Zhongyi] Changde Vocat Tech Coll, Basic Med Dept, Changde, Peoples R China.
通讯机构:
[Wang, Zuo] U;Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang City 421001, Peoples R China.
摘要:
Improvement of blood flow and promotion of angiogenesis are important therapeutic measures for the treatment of ischemic peripheral vascular diseases. Since apolipoprotein (a) (apo (a)) is a glycoprotein with repetitive kringle domains exhibiting 75% to 98% structural homology with plasminogen (Plg), apo (a) may also have a negative effect on endothelial progenitor cell (EPC)-induced angiogenesis through Plg-like inhibitory effects on EPC proliferation, adhesion, migration, and angiogenesis. To evaluate the effect of apo (a) on EPCs-induced angiogenesis, EPCs were isolated from the bone marrow of apo (a) transgenic mice, wild-type litter mates, and normal mice. These cells were cultured without or with apo (a) before transplantation. Hindlimb ischemia models were surgically induced in mice, which then received an intravenous injection of 3×105 EPCs. At 3, 7, and 14 days post EPC transplantation, the adhesion, migration abilities, and capillary density in calf muscles were assessed. Results indicate that apo (a) significantly reduced the adhesion and migration abilities of EPCs. Furthermore, the tubule-like formation of EPCs on Matrigel gels was damaged. In vivo experiments showed the homing of EPCs to ischemic peripheral vascular, and the number of capillary vessels decreased significantly in apo(a) transgenic mice. This study demonstrated that apo (a) could attenuate the adhesion, migration, and homing abilities of EPCs and could impair the angiogenesis ability of EPCs. © Copyright 2013, Mary Ann Liebert, Inc. 2013.
语种:
英文
展开
载脂蛋白A损伤小鼠骨髓源性EPCs血管发生能力及其机制
作者:
Wang Ren;Zhang Kai;Li Shuang;Tong Zhong-Yo;Li Guo-Hua;...
期刊:
生物化学与生物物理进展 ,2013年40(8):757-765 ISSN:1000-3282
通讯作者:
Wang Zuo
作者机构:
[Zhao Yue; Li Guo-Hua; Liu Feng-Tao; Wang Zuo; Lin Xiao-Long; Jiang Zhi-Sheng; Zhao Zhan-Zhi; Li Shuang; Wang Ren] Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.;[Zhao Yue; Li Guo-Hua; Liu Feng-Tao; Wang Zuo; Lin Xiao-Long; Jiang Zhi-Sheng; Zhao Zhan-Zhi; Li Shuang; Wang Ren] Univ South China, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Zhang Kai] Univ South China, ICU Dept, Affiliated Hosp 2, Hengyang 421001, Peoples R China.;[Tong Zhong-Yo] Changde Vocat Tech Coll Changde, Basic Med Dept, Changde 415000, Peoples R China.
通讯机构:
[Wang Zuo] U;Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.
关键词:
内皮祖细胞;载脂脂蛋白A;血管发生;骨髓
摘要:
改善血流、促进血管新生是缺血性外周血管疾病的重要治疗措施.由于载脂蛋白A(ApoA)与纤溶酶原(plasminogen,Plg)具有75%~98%的结构同源性,因此,ApoA也可能通过类似Plg的方式抑制内皮祖细胞(endothelial progenitor cells,EPCs)增殖、黏附及迁移而影响血管发生的能力.本文研究ApoA对EPCs 血管发生的影响及机制.为了编码人ApoA全长cDNA序列的pSG-5表达载体,转染COS-7细胞株后进行培养,收集培养液,免疫亲和层析法分离纯化ApoA蛋白;从转ApoA基因小鼠、野生型对照鼠及正常对照鼠骨髓分离培养EPCs,经ApoA处理后移植下肢缺血实验小鼠,于移植后第3、7、14天后观察ApoA对EPCs黏附、迁移及血管发生能力的影响.研究发现,ApoA能显著降低 EPCs的黏附、迁移能力,Matrigel胶上,EPCs血管腔样结构严重破坏,体内实验揭示,EPCs归巢至ApoA转基因小鼠缺血组织血管周围的数量及毛细血管数量显著减少.结果表明,ApoA能损伤EPCs的黏附、迁移及归巢,最终损伤EPCs的血管发生能力.
语种:
中文
展开
Hydrogen sulfide prevents H2O2-induced senescence in human umbilical vein endothelial cells through SIRT1 activation
作者:
Suo, Rong;Zhao, Zhan-Zhi;Tang, Zhi-Han;Ren, Zhong;Liu, Xing;...
期刊:
MOLECULAR MEDICINE REPORTS ,2013年7(6):1865-1870 ISSN:1791-2997
通讯作者:
Jiang, Zhi-Sheng
作者机构:
[Jiang, Zhi-Sheng] Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Zhi-Sheng] Univ South China, Inst Cardiovasc Dis, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Jiang, Zhi-Sheng] U;Univ South China, Inst Cardiovasc Dis, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
Cardiovascular;Oxidative stress;Sirtuin 1
摘要:
The aim of the present study was to investigate the attenuation of endothelial cell senescence by H2S and to explore the mechanisms underlying the anti-aging effects of H2S. Senescence was induced in human umbilical vein endothelial cells (HUVECs) by incubation in 25 ?mol/l H2O2 for 1 h. Senescence-associated β-galactosidase (SA-β-gal) activity was examined to determine the effects of H2S on senescent HUVECs. The results indicated that SA-β-gal activity in the H2O2-treated HUVECs was 11.2±1.06%, which was attenuated in the NaHS group. Pretreatment with nicotinamide (NAM), a sirtuin 1 (SIRT1) inhibitor, inhibited the reduction in senescence associated with H 2S. Immunoblot analyses revealed that SIRT1 levels in senescent HUVECs treated with NaHS (60 ?M) were indistinguishable from controls; however, analyses of SIRT1 activity indicated that SIRT1 enzyme activity was enhanced. In addition, we found that H2S improves the function of senescent HUVECs. The present study demonstrated that H2S protects against HUVEC senescence, potentially through modulation of SIRT1 activity. Furthermore, this study establishes a novel endothelial protective effect of H2S. Copyright © 2013 Spandidos Publications Ltd. All rights reserved.
语种:
英文
展开
FGF21通过FGFR1-ERK1/2-Elk-1通路抑制HepG2细胞载脂蛋白(a)表达
作者:
林小龙;何兴兰;马小峰;张凯;张海;...
作者机构:
南华大学心血管疾病研究所动脉硬化湖南省重点实验室,湖南省衡阳市421001
会议名称:
第十二次全国动脉硬化性疾病学术会议
会议时间:
2013-10-11
会议地点:
江苏苏州
会议论文集名称:
第十二次全国动脉硬化性疾病学术会议论文集
关键词:
载脂蛋白(a);FGFR1-ERK1/2-EIk-1通路;HepG2细胞
摘要:
目的 探讨FGF21对HepG2细胞中载脂蛋白(a)[Apo(a)]表达的影响及其作用机制.方法 以HepG2细胞为研究对象,用不同浓度FGF21(0、50、100、200及400 μg/L)或相同浓度FGF21(200 μg/L)处理细胞不同时间(0、6、12、24及48 h),用免疫组化、Western blot观察细胞Apo(a)蛋白水平的变化,real-time PCR观察Apo(a) mRNA变化、ELISA观察培养基中Apo(a)分泌情况,筛选出FGF21的最佳作用时间和浓度;通过应用ERK1/2抑制剂或转柒Elk-1 siRNA或FGFR1抑制剂,用Western blot 观察p-ERK1/2、T-ERK1/2、p-Elk-1、T-Elk-1、Apo(a)表达变化,免疫组化观察细胞Apo(a)变化,real-time PCR观察Apo(a) mRNA变化、ELISA观察培养基中Apo(a)分泌情况.结果 与对照组相比,FGF21在200 μg/L、400 μg/L时对Apo(a)表达影响最大,但200 μg/L与400 μg/L之间抑制效果无明显差别;而FGF21处理不同时间显示,在12、24及48 h均可明显减少Apo(a)表达,但三个时间段之间并无明显差异.FGF21+ ERK1/2抑制剂组与对照组相比Apo(a)表达无明显变化,与FGF21组相比Apo(a)表达明显增加,而Elk-1激活明显受到抑制,表明ERK1/2参与抑制HepG2细胞Apo(a)表达的调节;FGF21+Elk-1 siRNA组与对照组相比Apo(a)表达无明显变化,而与FGF21组相比Apo(a)表达明显增加,表明Elk-1参与FGF21抑制HepG2细胞Apo(a)表达;FGF21+ FGFR1抑制剂组与对照组相比Apo(a)表达无明显变化,而与FGF21组相比Apo (a)表达明显增加,而这表明FGF21通过ERK1/2-Elk-1抑制HepG2细胞Apo (a)表达是由FGFR1所介导的.结论 FGF21可以通过FGFR1-ERK1/2-Elk-1通路抑制HepG2细胞Apo(a)表达.
语种:
中文
展开
Oxidized Lipoprotein(a) Increases Endothelial Cell Monolayer Permeability via ROS Generation
作者:
Wei, Deng-heng;Zhang, Xiao-lei;Wang, Ren;Zeng, Jun-fa;Zhang, Kai;...
期刊:
Lipids ,2013年48(6):579-586 ISSN:0024-4201
通讯作者:
Wang, Zuo
作者机构:
[Wei, Deng-heng; Wang, Ren; Jiang, Zhi-sheng; Zhang, Xiao-lei; Yang, Jian; Zeng, Jun-fa; Li, Shuang; Lin, Xiao-long; Wang, Zuo; Zhang, Kai] Univ South China, Key Lab Arteriosclerol Hunan Prov, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.;[Zhang, Xiao-lei] Huaiyin Adv Vocat & Tech Sch Hlth, Lab Digest Tract Tumor, Huaian 223300, Peoples R China.;[Wang, Gui-xue] Chongqing Univ, Key Lab Biorheol Sci & Technol, Minist Educ, Bioengn Coll, Chongqing 400044, Peoples R China.
通讯机构:
[Wang, Zuo] U;Univ South China, Key Lab Arteriosclerol Hunan Prov, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.
关键词:
Lipid chemistry;Lipid metabolism;Inflammation;Physiology;Lipid peroxidation;Oxidized lipids
摘要:
Oxidized lipoprotein(a) (oxLp(a)) is a more potent marker of atherogenesis than native Lp(a). However, the molecular mechanisms of oxLp(a) activity are not clear. Reactive oxygen species (ROS) have recently been suggested as acting as intracellular second messengers. In this study, the effects of oxLp(a) on endothelial cell monolayer permeability and the role of reactive oxygen species (ROS) generation in these effects were investigated. Our results showed that oxLp(a) inhibited desmoglein-1 (DSG1) and desmocollin-2 (DSC2) expression at both mRNA and protein levels in a dose- and time-dependent manner, and increased the generation of cellular ROS. Down-regulation of DSG1 and DSC2 was strengthened by pretreatment with H2O2 and attenuated by superoxide dismutase (SOD) treatment. Furthermore, oxLp(a) increased endothelial cell monolayer permeability, and this effect was enhanced by H2O2 and blunted by SOD. Taken together, these results demonstrate that oxLp(a) increases endothelial cell monolayer permeability, which is mediated at least in part via ROS generation.
语种:
英文
展开
Blood pressure reducing effects of piromelatine and melatonin in spontaneously hypertensive rats.
作者:
Huang, L.;Zhang, C.;Hou, Y.;Laudon, M.;She, M.;...
期刊:
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES ,2013年17(18):2449-2456 ISSN:1128-3602
通讯作者:
Yin, W.
作者机构:
[Zhang, C.; Yin, W.; Hou, Y.; Huang, L.; He, P.] Univ South China, Key Lab Arteriosclerosis Hunan Prov, Inst Cardiovasc Res, Hengyang, Hunan, Peoples R China.;[Huang, L.; Wang, H.] Univ South China, Dept Operat Surg, Hengyang, Hunan, Peoples R China.;[Yin, W.; She, M.; Ding, L.; Yang, S.] Univ South China, Dept Biochem & Mol Biol, Sch Life Sci & Technol, Hengyang, Hunan, Peoples R China.;[Laudon, M.] Neurim Pharmaceut Ltd, Drug Discovery, Tel Aviv, Israel.;[Wang, Z.] Univ South China, Dept Lab Anim Sci, Hengyang, Hunan, Peoples R China.
通讯机构:
[Yin, W.] U;Univ South China, Key Lab Arteriosclerosis Hunan Prov, Inst Cardiovasc Res, Hengyang, Hunan, Peoples R China.
关键词:
Piromelatine;Melatonin;Hypertension;Spontaneously hypertensive rats;Metabolic diseases
摘要:
Recently, widespread interest has grown regarding melatonin treatment of hypertension including its cardioprotective effects. Studies in rodents indicate that melatonin plays a role in the pathogenesis of hypertension in rats with metabolic syndrome. Piromelatine, a melatonin agonist, serotonin 5-HT-1A and 5-HT-1D agonist and serotonin 5-HT2B antagonist is a multimodal agent with sleep promoting, anti-diabetic, analgesic, anti-neurodegenerative, anxiolytic and antidepressant potential, currently in development for the treatment of insomnia. In this report we assessed the effects of piromelatine and melatonin treatment on blood pressure in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Five groups of 12-wk-old rats (10/group) were treated for 5 weeks with a vehicle, piromelatine (5, 15 and 50 mg/kg BW) and melatonin (10 mg/kg BW) and an age-matched WKY control group. Systolic blood pressure (tail-cuff method) was measured weekly at 9:00 a.m. and at 9:00 p.m. The rats body weight, plasma glucose, insulin, triglyceride, adiponectin, total cholesterol, HDL and LDL/VLDL cholesterol were also measured. Our results showed that both piromelatine and melatonin reduced SHR blood pressure significantly both during the morning and the evening. Piromelatine, but not melatonin, also reduced SHR body weight gain and both significantly decreased plasma glucose and insulin levels and increased adiponectin levels. Piromelatine, similar to melatonin, has an antihypertensive effect and also attenuates body weight, improves metabolic profiles and might be useful in the treatment of hypertension and the metabolic syndrome.
语种:
英文
展开
FGF21通过FGFRl-ERKI/2-Elk-1通路抑制HepG2细胞载脂蛋白(a)表达
作者:
林小龙;何兴兰;马小峰;张凯;张海;...
期刊:
中国动脉硬化杂志 ,2013年21(9):I0039-I0039 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化湖南省重点实验室,湖南省衡阳市421001
关键词:
脂蛋白(a);2-Elk-1通路;HEPG2细胞
摘要:
目的探讨FGF21对HepG2细胞中载脂蛋白(a)[Apo(a)]表达的影响及其作用机制。方法以HepG2细胞为研究对象,用不同浓度FGF21(O、50、100、200及400μg/L)或相同浓度FGF21(200μg/L)处理细胞不同时间(0、6、12、24及48h),用免疫组化、Westernblot观察细胞Apo(a)蛋白水平的变化,real—timePCR观察Apo(a)mRNA变化、ELISA观察培养基中Apo(a)分泌情况,
语种:
中文
展开
载脂蛋白(a)对小鼠骨髓源性内皮祖细胞血管生成能力的影响
作者:
王仁;张凯;刘峰涛;赵战芝;赵岳;...
期刊:
中国动脉硬化杂志 ,2013年(9):I0041-I0041 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化湖南省重点实验室;南华大学附属第二医院ICU病房;南华大学机能学实验中心
关键词:
内皮祖细胞;载脂蛋白(a);血管新生
摘要:
背景改善血流、促进血管新生是缺血性外周血管疾病的重要治疗措施。由于载脂蛋白(a)[Apo(a)]与纤溶酶原具有75%~98%的结构同源性,因此,Apo(a)也可能通过类似纤溶酶原的方式抑制内皮祖细胞(EPC)增殖、黏附及迁移而影响血管发生能力。目的研究Apo(a)对EPC血管发生的影响及机制。方法编码人Apo(a)全长eDNA序列的pSG-5表达载体转染COS-7细胞株后进行培养,收集培养液,免疫亲和层析法分离纯化Apo(a)蛋白;从转Apo(a)基因小鼠、野生型对照鼠及正常对照鼠骨髓分离培养EPC,经Apo(a)处理后移植下肢缺血实验小鼠,于移植后第3、7、14天后观察Apo(a)对EPC黏附、迁移及血管发生能力的影响。结果Apo(a)能显著降低EPC黏附、迁移能力,EPC血管腔样结构严重破坏;体内实验揭示,EPC归巢至Apo(a)转基因小鼠缺血组织血管周围的数量及毛细血管数量显著减少。结论Apo(a)能损伤EPC黏附、迁移及归巢,最终损伤EPC的血管发生能力。
语种:
中文
展开
FGF21对THP-1源性巨噬细胞胆固醇流出的影响及其机制
作者:
唐雅玲;林小龙;何兴兰;张海;张凯;...
期刊:
中国动脉硬化杂志 ,2013年21(9):I0040-I0040 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化湖南省重点实验室,湖南省衡阳市421001
会议名称:
第十二次全国动脉硬化性疾病学术会议
会议时间:
2013-10-11
会议地点:
江苏苏州
会议论文集名称:
第十二次全国动脉硬化性疾病学术会议论文集
关键词:
胆固醇流出;脂质蓄积;泡沫细胞
摘要:
目的 探讨FGF21对THP-1源性泡沫细胞胆固醇流出的影响及机制。方法 采用体外培养的THP-1细胞作为研究对象,用PMA诱导为巨噬细胞,加入ox-LDL(50 mg/L)诱导泡沫细胞,同时加入不同浓度的FGF21处理,油红O观察细胞的脂质蓄积情况,高效液相色谱法测定细胞内总胆固醇(TC)、游离胆固醇(FC)、胆固醇酯(CE)变化,液体闪烁计数仪测定胆固醇流出率,低pH值ELISA测定细胞内cAMP水平,采用实时定量PCR和蛋白印迹法分别检测细胞中ABCA1、ABCG1、LXRα、PPARγ的表达变化。结果 泡沫细胞模型组脂质蓄积远多于正常组。而FGF21处理组(200 ng/L、400 ng/L)与泡沫细胞模型组相比脂质蓄积明显减少,并可以显著减少细胞内TC、FC、CE及CE/TC,同时显著提高细胞胆固醇流出率、细胞内cAMP水平及ABCA1、ABCG1表达。结论 FGF21可以促进THP-1源性巨噬细胞ABCA1、ABCG1表达促进细胞内胆固醇流出,抑制泡沫细胞形成,其机制可能是通过上调细胞内cAMP水平起作用。
语种:
中文
展开
亲环素A对氧化型低密度脂蛋白诱导的RAW264.7细胞中NF-κB蛋白表达的影响
作者:
许选选;尹凯;李涛;李金凤;涂剑;...
期刊:
中国动脉硬化杂志 ,2013年21(4):311-314 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化学湖南省重点实验室,湖南省衡阳市,421001;南华大学药物药理研究所,湖南省衡阳市,421001
关键词:
亲环素A;氧化型低密度脂蛋白;核因子κB
摘要:
目的 观察亲环素A对氧化型低密度脂蛋白诱导的RAW264.7细胞中核因子κB (NF-κB)表达的影响.方法 Western blot检测氧化型低密度脂蛋白处理RAW264.7细胞不同时间亲环素A和NF-κB蛋白的表达,siRNA沉降亲环素A后再用Western blot检测氧化型低密度脂蛋白对RAW264.7细胞中NF-κB蛋白表达的影响.结果 氧化型低密度脂蛋白能够上调RAW264.7细胞中亲环素A和NF-κB蛋白的表达,siRNA沉降亲环素A能降低细胞中NF-κB蛋白的表达.结论 亲环素A表达的改变能影响氧化型低密度脂蛋白诱导的RAW264.7细胞中NF-κB的蛋白表达.
语种:
中文
展开
Cathepsin L stimulates autophagy and inhibits apoptosis of ox-LDL-induced endothelial cells: Potential role in atherosclerosis
作者:
Wei, Dang-Heng* ;Jia, Xiao-Ying;Liu, Yang-Hui;Guo, Feng-Xia;Tang, Zhi-Han;...
期刊:
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE ,2013年31(2):400-406 ISSN:1107-3756
通讯作者:
Wei, Dang-Heng
作者机构:
[Jia, Xiao-Ying; Tang, Zhi-Han; Jian, Zhi-Sheng; Wei, Dang-Heng; Li, Xiao-Hong; Liu, Yang-Hui; Guo, Feng-Xia; Wang, Zuo; Liu, Lu-Shan] Univ S China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Jia, Xiao-Ying] Xiangnan Univ, Dept Nursing, Chenzhou 423000, Peoples R China.;[Wang, Gui-Xue; Wei, Dang-Heng] Chongqing Univ, Bioengn Coll, Minist Educ, Key Lab Biorheol Sci & Technol, Chongqing 400044, Peoples R China.;[Wei, Dang-Heng; Ruan, Chang-Geng] Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Hematol, Key Lab Thrombosis & Hemostasis,Minist Hlth, Suzhou 215006, Peoples R China.;[Wei, Dang-Heng] Univ S China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang 42001, Peoples R China.
通讯机构:
[Wei, Dang-Heng] U;Univ S China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang 42001, Peoples R China.
关键词:
Apoptosis;Autophagy;Cathepsin L;Endothelial cell;Oxidized low-density lipoprotein;Permeability
摘要:
The activation of endothelial cells by oxidized low-density lipoprotein (ox-LDL) with subsequent increases in endothelial permeability occurs in the early stage of atherosclerosis. Cathepsin L (CATL) is one of the cysteine proteases and has been implicated in advanced atherosclerotic lesions and plaque instability. This study aimed to explore the role of CATL in ox-LDL-induced early atherosclerotic events and to delineate the underlying mechanism. Results showed that ox-LDL upregulated CATL protein levels and activation in human umbilical vein endothelial cells (ECs) in a concentration-dependent manner and stimulated EC autophagy and apoptosis and increased EC monolayer permeability. Concomitantly, VE-cadherin expression was decreased. When ECs were pretreated with a CATL inhibitor, ox-LDL-induced autophagy was inhibited while apoptosis was further increased. In addition, the VE-cadherin protein level was increased, and the EC monolayer permeability was reduced. Taken together, the present study showed that the upregulated expression and activation of CATL induced by ox-LDL, increased EC autophagy and antagonized EC apoptosis, which partly neutralized the effect of increased EC monolayer permeability mediated by the downregulation of VE-cadherin. Thus, the proatherogenic effect of CATL was partly neutralized by inducing autophagy and inhibiting apoptosis in early stages of atherosclerosis.
语种:
英文
展开
Increased trans-endothelial cells permeability induced by oxidized lipoprotein(a) relates to reactive oxygen species generation and desmogleins expression
作者:
Wang, Z.* ;Yang, J.;Zhang, X.-L.;Ma, X.-F.;Wang, R.;...
期刊:
IFMBE Proceedings ,2013年39(1):672-676 ISSN:1680-0737
通讯作者:
Wang, Z.
作者机构:
Zhang;X.-l.
通讯机构:
Institute of Cardiovascular Research, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, China
关键词:
desmogleins;oxidized-lipoprotein(a);permeability;reactive oxygen species;superoxide dismutase
摘要:
Aim: we aim at measurement enhanced effect of oxidized lipoprotien(a) [oxLp(a)] on permeability of monolayer endothelial cells and relationship with reactive oxygen spe-cies(ROS) generation and desmogleins(DSGs) expression. Methods and Results : Trans-endothelial permeability was assayed by transwell and reactive oxygen species(ROS) was determined by DCFH-DA staining. RT-PCR was carried out to determine DSG1 and DSC2 expression in mRNA, respectively. Trans-endothelial permeability was enhanced by oxLP(a) dose and time dependently. The most marked effect appeared at a concentration of 100 mg/L, Trans-endothelial permeability reached the maximum value after 2 h of FITC-dextran addition, and then gradually decreased after 4 h. oxLp(a) induces the generation of cellular reactive oxygen species (ROS), and this effect could be inhibited by superoxide dismutase(SOD). Incubation of HUVECs with oxLp(a) resulted in a dose and time-dependent down-regulation of DSG1 and DSC2 expression at transcriptional level. Conclusion : permeability of monolayer endothelial cells was enhanced by oxLp(a) and it is related to up-regulating ROS formation and down-regulating desmogleins expression. © 2013 Springer-Verlag.
语种:
英文
展开
载脂蛋白(a)对小鼠骨髓源性内皮祖细胞血管生成能力的影响
作者:
王仁;张凯;刘峰涛;赵战芝;赵岳;...
作者机构:
南华大学心血管疾病研究所动脉硬化湖南省重点实验室,湖南省衡阳市421001;南华大学附属第二医院ICU病房,湖南省衡阳市421001;南华大学机能学实验中心,湖南省衡阳市421001
会议名称:
第十二次全国动脉硬化性疾病学术会议
会议时间:
2013-10-11
会议地点:
江苏苏州
会议论文集名称:
第十二次全国动脉硬化性疾病学术会议论文集
关键词:
内皮祖细胞;载脂蛋白(a);血管新生
摘要:
背景 改善血流、促进血管新生是缺血性外周血管疾病的重要治疗措施。由于载脂蛋白(a)[Apo(a)]与纤溶酶原具有75%~98%的结构同源性,因此,Apo (a)也可能通过类似纤溶酶原的方式抑制内皮祖细胞(EPC)增殖、黏附及迁移而影响血管发生能力。目的 研究Apo(a)对EPC血管发生的影响及机制。方法 编码人Apo(a)全长cDNA序列的pSG-5表达载体转染COS-7细胞株后进行培养,收集培养液,免疫亲和层析法分离纯化Apo(a)蛋白;从转Apo (a)基因小鼠、野生型对照鼠及正常对照鼠骨髓分离培养EPC,经Apo(a)处理后移植下肢缺血实验小鼠,于移植后第3、7、14天后观察Apo(a)对EPC黏附、迁移及血管发生能力的影响。结果 Apo(a)能显著降低EPC黏附、迁移能力,EPC血管腔样结构严重破坏;体内实验揭示,EPC归巢至Apo(a)转基因小鼠缺血组织血管周围的数量及毛细血管数量显著减少。结论 Apo (a)能损伤EPC黏附、迁移及归巢,最终损伤EPC的血管发生能力。
语种:
中文
展开
影响血管内皮细胞自噬的因素及其相关机制探讨
作者:
Lin Xiao-Long;Ma Xiao-Feng;Li Shuang;Zhao Yue;Wang Zuo*
期刊:
生物化学与生物物理进展 ,2012年39(3):234-240 ISSN:1000-3282
通讯作者:
Wang Zuo
作者机构:
[Zhao Yue; Ma Xiao-Feng; Wang Zuo; Lin Xiao-Long; Li Shuang] Univ S China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.
通讯机构:
[Wang Zuo] U;Univ S China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.
关键词:
内皮细胞;自噬;氧化低密度脂蛋白;整联蛋白β4
摘要:
自噬对维持细胞自身的稳定及细胞成分更新、保持正常的生理状态起着至关重要的作用.机体在生理和病理过程中都存在自噬,基础状态下的自噬对细胞具有保护和修复作用,而自噬过度激活会引起细胞的损伤及死亡.近年来,对自噬的研究主要集中于肿瘤细胞,而对正常细胞的自噬研究较少.血管内皮细胞作为人体中最活跃的细胞之一,其功能变化与心血管疾病的发生和发展有密切相关.本文对影响血管内皮细胞自噬的因素及其相关机制进行综述.
语种:
中文
展开
氧化型低密度脂蛋白对人脐静脉内皮细胞TET2表达及自噬的影响
作者:
危当恒;贾小英;刘艳辉;郭凤霞;刘慧婷;...
期刊:
中国动脉硬化杂志 ,2012年20(11):972-975 ISSN:1007-3949
作者机构:
[危当恒; 阮长耿] 苏州大学附属第一医院;[贾小英; 刘艳辉; 郭凤霞; 刘慧婷; 王佐] 南华大学心血管疾病研究所
关键词:
氧化型低密度脂蛋白;血管内皮细胞;自噬
摘要:
目的观察氧化型低密度脂蛋白对人脐静脉内皮细胞自噬的影响及其调节机制。方法氧化型低密度脂蛋白孵育人脐静脉内皮细胞24h, RT-PCR检测TET2 mRNA表达,Western blot检测TET2以及自噬标记物Beclin 1、LC3的表达。TET2 siRNA转染人脐静脉内皮细胞,Western blot检测Beclin 1、LC3的表达。结果人脐静脉内皮细胞经不同浓度氧化型低密度脂蛋白孵育24h后,浓度依赖性地下调TET2 mRNA以及蛋白的表达(P<0.05),并且下调Beclin 1表达以及LC3Ⅱ/LC3Ⅰ的比值。TET2 siRNA转染人脐静脉内皮细胞后,Beclin 1表达以及LC3Ⅱ/LC3Ⅰ的比值明显降低。结论氧化型低密度脂蛋白促进人脐静脉内皮细胞自噬,可能与下调TET2表达相关。
语种:
中文
展开
氨氯地平下调内皮细胞源性PDGF-B表达抑制平滑肌细胞增殖和迁移
作者:
何谨;孟军;白洁;涂剑;许选选;...
期刊:
中国动脉硬化杂志 ,2012年20(12):1093-1096 ISSN:1007-3949
作者机构:
南华大学附属第一医院,湖南省衡阳市,421001;南华大学药物药理研究所,湖南省衡阳市,421001;南华大学医学院,湖南省衡阳市,421001
关键词:
氨氯地平;人脐静脉内皮细胞;血小板源性生长因子B;人脐动脉平滑肌细胞;细胞增殖和迁移
摘要:
目的 观察人脐静脉内皮细胞12(HUVEC-12)受氧化型低密度脂蛋白刺激及氨氯地平作用后,血小板源生长因子B(PDGF-B)的内源性表达改变对人脐动脉平滑肌细胞(HUASMC)增殖和迁移的影响.方法 酶联免疫吸附法检测不同浓度氨氯地平预孵育对氧化型低密度脂蛋白诱导的HUVEC-12细胞培养上清液中PDGF-B蛋白的表达.选择10.0 μmol/L氨氯地平和20 μmol/L PDGF-B抗体分别预孵育HUASMC 30 min,然后与PDGF-B上清液共同孵育24h,噻唑蓝法检测不同细胞增殖能力的变化,Transwell迁移实验检测细胞迁移能力的改变.结果 氨氯地平可下调氧化型低密度脂蛋白诱导的HUVEC-12细胞培养上清液中PDGF-B的蛋白表达,并能使预孵育HUASMC组细胞的增殖和迁移能力明显降低.结论 氨氯地平下调内皮细胞源性PDGF-B的表达可抑制HUA-SMC的增殖和迁移.
语种:
中文
展开
Calphostin C抑制脂肪分化相关蛋白诱导的ACAT1表达
作者:
袁中华;陶媛;刘清南;黄谙非;刘晓辉;...
期刊:
中国动脉硬化杂志 ,2012年20(12):1057-1063 ISSN:1007-3949
作者机构:
[袁中华; 陶媛; 唐朝克; 易光辉; 王佐] 南华大学心血管疾病研究所;[刘清南] 益阳医学高等专科学校护理系基础护理学教研室;[黄谙非] 深圳市西丽医院病理科;[刘晓辉] 苏州大学唐仲英血液学研究中心;[田国平] 南华大学附属第二医院心内科
关键词:
脂肪分化相关蛋白;乙酰辅酶A:胆固醇酰基转移酶1
摘要:
目的我们已经发现adipophilin通过改变乙酰辅酶A∶胆固醇酰基转移酶1(ACAT1)的表达来促进细胞内脂质蓄积,病理状态下形成泡沫细胞,成为动脉粥样硬化的始动因素。本研究旨在探讨该过程所涉及的信号通路,阐明adipophilin引起细胞内脂质积聚的机制。方法通过克隆adipophilin基因,构建逆转录病毒载体pQCXIP-HA-Adi,使用siRNA技术构建pSuper-retro-adipophilin siRNA逆转录病毒载体,包装病毒后,感染RAW264.7细胞,筛选后获得高或低表达adipophilin的细胞。将该细胞分别与300 nmol/L PKC抑制剂Calphostin C孵育16 h或同时再加入50 mg/L氧化型低密度脂蛋白(ox-LDL)共孵育,应用RT-PCR和Western blot检测细胞内ACAT1的表达。当低表达adipophilin的细胞与Calphostin C共孵育时,在不同的时间点取样,RT-PCR和Westernblot检测各时间点细胞内ACAT1的表达。结果高表达adipophilin细胞中ACAT1表达增加,低表达adipophilin细胞中ACAT1表达减少。无论在高或低表达adipophilin的细胞中,Calphostin C能够抑制ACAT1的表达,与不孵育Calphostin C组相比差别有显著性。与ox-LDL孵育使高表达adipophilin的细胞荷脂,同样能够发现Calphostin C抑制ACAT1的表达。低表达adipophilin的细胞与Calphostin C共孵育1 h后,ACAT1 mRNA开始下降;孵育8 h后,ACAT1蛋白开始下降;孵育16 h后ACAT1 mRNA及蛋白表达均明显下降,与对照组相比差别有显著性。高及低表达adipophilin或负荷脂质状态下,Calphostin C能够时间依赖性的抑制ACAT1的表达。结论adipophilin引起细胞内脂质积聚的机制可能是,PKC信号分子作用于adipophilin,并进一步影响ACAT1的表达,最终导致细胞内脂质积聚。
语种:
中文
展开