作者： Wang, Zuo;Tang, Zhi-Han;Lv, Yun-Chen;Liu, Lu-Shan;Jiang, Zhi-Sheng

期刊： Lecture Notes in Electrical Engineering,2012年129 LNEE(VOL. 6):527-533 ISSN：1876-1100

通讯作者： Wang, Z.

作者机构： [Lv, Yun-Chen; Wang, Zuo; Liu, Lu-Shan; Tang, Zhi-Han; Jiang, Zhi-Sheng] Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, 421001 Heng Yang, China

摘要： To determine whether the proapoptotic effect of proprotein-convertasae cubtilisin/kexin 9 related to caspase3 activation by informatics analysis. The blank control group, the transfection regent control group, the negative control group and the 80 nmol/L PCSK9 siRNA+80μg/ml oxLDL group were established simultaneously with the participation of HUVEC-12 which was incubated with 80μg/ml oxLDL for 24hr. Expression of caspase3 was measured by western blot. In order to find the similarity of sequence and the existence of a common conservative motif, comparison was made among PCSK9, caspase8 and caspase9 by bioinformatics methods. An inhibitory effect of PCSK9 siRNA on expression of caspase3 was observed in experiments. The sequence similarity of PCSK9, caspase8 and caspase9 was 22.14%. There was a similar secondary structure such as helix, strand, turn and coil in C-terminal of PCSK9 and caspase9. The similarity also can be found in the profile of PCSK9 and caspase9, which explains the common cleft relating to their similar enzyme activity in their abdomen. Finally, there were similar motifs when comparing PCSK9 with caspase9, while the proapoptotic capacity of PCSK9 has association with its activation effect on caspase3. ©2012 Springer-Verlag Berlin Heidelberg.

语种： 英文

作者： Wang Zuo*;Su Wei;Zhou Xiao-Feng;Zhang Kai;Li Shuang;...

期刊： 生物化学与生物物理进展,2012年39(2):168-174 ISSN：1000-3282

通讯作者： Wang Zuo

作者机构： [Ma Xiao-Feng; Wang Zuo; Jiang Zhi-Sheng; Zhang Kai; Li Shuang; Su Wei] Univ S China, Key Lab Arteriosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang 421001, Peoples R China.;[Zhou Xiao-Feng] Qinghai Univ, Affiliated Hosp, Dept Pathol, Xining 810001, Peoples R China.

通讯机构： [Wang Zuo] U;Univ S China, Key Lab Arteriosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang 421001, Peoples R China.

关键词： 基质细胞衍生因子1α;动脉粥样硬化;肿瘤坏死因子α;核因子-κB

摘要： 探索CXCR4阻断剂AMD3100促进apoE-/-小鼠动脉粥样硬化病变的分子机制.36只8周龄雄性apoE-/-小鼠随机分为三组:普食组、高脂组和AMD3100组.ELISA法测血清基质细胞衍生因子1α(SDF-1α)水平,采用氧化酶法测定apoE-/-小鼠血清中三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)含量.HE染色检测apoE-/-小鼠主动脉根部横切面动脉粥样硬化病变.免疫组织化学检测小鼠胸主动脉CXCR4表达.RT-PCR和Western blot分别检测小鼠动脉组织TNF-α、NF-κB mRNA和蛋白质表达.AMD3100组小鼠主动脉根部横截面的动脉粥样硬化病变较高脂组严重,AMD3100组小鼠胸腹主动脉炎症因子TNF-α、NF-κB的mRNA水平和蛋白质表达增高,但血脂TG、TC、HDL-C和LDL-C含量与高脂组均无显著性差异.AMD3100组小鼠外周血SDF-1α水平和动脉壁CXCR4表达低于高脂组.结果表明:AMD3100通过上调炎性因子表达及下调SDF-1/CXCR4轴促进apoE-/-小鼠动脉粥样硬化病变.

语种： 中文

作者： 杨简（综述）;涂玉林;王佐（审校）

期刊： 中国动脉硬化杂志,2012年20(5):472-476 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;[杨简（综述）] 南华大学

关键词： 脂蛋白(a);载脂蛋白(a);动脉粥样硬化

摘要： 脂蛋白（a）由低密度脂蛋白和载脂蛋白（a）组成。高血浆脂蛋白（a）水平是动脉粥样硬化和心盖管疾病的独立危险因素。脂蛋白（a）不但能参与动脉粥样硬化斑块的形成，还能影响抗炎机制和血管壁中促凝与抗凝因子的平衡。血浆脂蛋白（a）水平的个体差异很大，主要受遗传因素控制。血浆脂蛋白（a）水平对药理和非药理因素都不敏感，临床上缺乏高效安全降低脂蛋白（a）水平的治疗方法。近年，科研工作者发现反义寡核苷酸链和人工合成的肽链等可以降低脂蛋白（a）水平，但用于临床治疗还需进一步研究。本文拟对近年来脂蛋白（a）与动脉粥样硬化研究的新进展进行综述。

语种： 中文

作者： Liu, Xiaoping;Tang, Hailin;Wang, Zeyou;Huang, Chen;Zhang, Zuping;...

期刊： Journal of Neuro-Oncology,2012年107(3):479-485 ISSN：0167-594X

通讯作者： Wu, Minghua

作者机构： [Wu, Minghua; She, Xiaoling; Tang, Hailin; Wang, Zeyou; Zhang, Zuping; Li, Guiyuan; Liu, Xiaoping] Cent S Univ, Canc Res Inst, Changsha, Hunan, Peoples R China.;[Wu, Minghua; She, Xiaoling; Tang, Hailin; Wang, Zeyou; Zhang, Zuping; Li, Guiyuan; Liu, Xiaoping] Cent S Univ, Dis Genome Res Ctr, Changsha, Hunan, Peoples R China.;[Wu, Minghua; She, Xiaoling; Tang, Hailin; Wang, Zeyou; Zhang, Zuping; Li, Guiyuan; Liu, Xiaoping] Minist Educ, Key Lab Carcinogenesis & Canc Invas, Changsha, Hunan, Peoples R China.;[Wu, Minghua; She, Xiaoling; Tang, Hailin; Wang, Zeyou; Zhang, Zuping; Li, Guiyuan; Liu, Xiaoping] Minist Hlth, Key Lab Carcinogenesis, Changsha, Hunan, Peoples R China.;[Tang, Hailin] Univ S China, Canc Res Inst, Hengyang 421001, Peoples R China.

通讯机构： [Wu, Minghua] C;Cent S Univ, Canc Res Inst, 110 Xiangya Rd, Changsha, Hunan, Peoples R China.

关键词： Glioma;F10;Hypomethylation;Prognosis

摘要： Tumors are usually characterized by an imbalance in cytosine methylation, including hypomethylation of CpG islands. In this study, bisulfite sequencing PCR was used to assess the promoter methylation status of coagulation factor X (F10) gene in tumors of 96 glioma patients and in glioma cells U251, SF767, and SF126, and the effect of promoter hypomethylation on protein expression was evaluated immunohistochemically. The study showed that the demethylation ratio of F10 in SF126, SF767, and U251 cells was 38.6, 26.4, and 24.3% respectively. Hypomethylation of F10 was detected in 82.3% of glioma specimens and in no normal brain tissues, with significant correlation with its protein expression. However there was no remarkable relationship between F10 hypomethylation and sex, age, and advanced tumor grade. The correlation between F10 hypomethylation, protein expression, and overall survival (OS) was statistically significant. Hypomethylation of F10 promoter in gliomas accounted for F10 encoding protein FX overexpression and aggressive biological behavior in a subset of patients. Furthermore, in the F10 hypomethylation group, OS was shorter for patients with F10 overexpression than for those without. Detection of these epigenetic changes in tumors may provide important information regarding prognosis.

语种： 英文

作者： Liu, Xiaoping;Tang, Hailin;Zhang, Zuping;Li, Wenjuan;Wang, Zeyou;...

期刊： Brain Research,2011年1391:125-131 ISSN：0006-8993

通讯作者： Wu, Minghua

作者机构： [Wu, Minghua; Tang, Hailin; Zhang, Zuping; Li, Wenjuan; Wang, Zeyou; Zheng, Ying; Li, Guiyuan; Liu, Xiaoping] Cent S Univ, Canc Res Inst, Changsha, Hunan, Peoples R China.;[Tang, Hailin] Univ S China, Canc Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Wu, Minghua] Cent S Univ, Canc Res Inst, 110 Xiangya Rd, Changsha, Hunan, Peoples R China.

通讯机构： [Wu, Minghua] C;Cent S Univ, Canc Res Inst, 110 Xiangya Rd, Changsha, Hunan, Peoples R China.

关键词： Hypomethylation;POTEH;Glioma;Prognosis

摘要： POTE ankyrin domain family, member H (POTEH) belongs to POTE family, which expresses in many cancers. In this study, methylation status of POTEH promoter and its correlation with clinicopathological parameters were evaluated in glioma tissues and cells. Bisulfite sequencing PCR was carried out to investigate the promoter methylation status of POTEH in tumor of 96 glioma patients and glioma cells U251, SF767, and SF126. The effect of promoter hypomethylation on protein expression was evaluated by immunohistochemistry. POTEH was hypomethylated in 81.3% gliomas and none in normal brain tissues, and correlated significantly with its protein expression. But there was no remarkable relationship between sex, age, advanced tumor grade and POTEH hypomethylation. With the grade progressing, POTEH protein expression was enhanced. The correlation between POTEH hypomethylation, protein expression and overall survival was statistically significant. In POTEH hypomethylation group, patients with POTEH high expression had shorter overall survival than those with low expression. Hypomethylation of POTEH promoter in gliomas accounted for POTEH protein overexpression and poor outcome in a subset of patients. Detection of these epigenetic changes in tumors may provide information regarding prognosis. © 2011 Elsevier B.V.

语种： 英文

作者： Tang, Hailin;Liu, Xiaoping;Wang, Zeyou;She, Xiaoling;Zeng, Xi;...

期刊： Brain Research,2011年1390:21-32 ISSN：0006-8993

通讯作者： Wu, Minghua

作者机构： [She, Xiaoling; Zeng, Fang; Wang, Zeyou; Li, Xiaoling; Guo, Xiaofang; Liao, Qianjin; Wu, Minghua; Tang, Hailin; Deng, Min; Wang, Rang; Zeng, Xi; Li, Guiyuan; Liu, Xiaoping] Cent S Univ, Canc Res Inst, Changsha 410078, Hunan, Peoples R China.;[Liao, Qianjin; Tang, Hailin; Deng, Min; Zeng, Xi] Univ S China, Canc Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Wu, Minghua] Cent S Univ, Canc Res Inst, 110 Xiang Ya Rd, Changsha 410078, Hunan, Peoples R China.

通讯机构： [Wu, Minghua] C;Cent S Univ, Canc Res Inst, 110 Xiang Ya Rd, Changsha 410078, Hunan, Peoples R China.

关键词： Biomarker;Carcinogenesis;Glioma;Leucine-rich repeat C4;hsa-miR-381

摘要： LRRC4 is not only a brain-specific gene, but it has also been identified as a tumor suppressor gene for glioma. Promoter methylation of LRRC4 is frequently involved in the inactivation in glioma. MiRNA-mediated gene regulation has recently been demonstrated to play an important role in multiple biological processes related to cancer, including glioma. In this study, we demonstrated that a small regulatory microRNA, hsa-miR-381, an "oncomir", had a major role in glioma progression and that LRRC4 was a target of hsa-miR-381. By regulating LRRC4, hsa-miR-381 increased the in vitro and in vivo proliferation of glioma cells, and this action was associated with decreased inhibition of MEK/ERK and AKT signaling. Conversely, LRRC4, as a glioma suppressor, inhibited the endogenous expression of hsa-miR-381 and decreased cell proliferation and tumor growth. The interaction of hsa-miR-381 and LRRC4 is involved in the pathogenesis of glioma. In addition, the stable expression of hsa-miR-381 in blood provides a novel and promising diagnostic biomarker, and anti-hsa-miR-381 "antagomir" may be an ideal target for glioma therapy. © 2011 Elsevier B.V. All rights reserved.

语种： 英文

作者： 刘峰涛;任重;唐志晗;王仁;刘录山;...

期刊： 中国动脉硬化杂志,2011年(3):255 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

关键词： 动脉粥样硬化

摘要： 目的探讨HDL3氧化修饰后对人脐静脉内皮细胞株HUVEC-12细胞组织型纤溶酶原激活物(tissue plasminogen activator;t-PA)表达的影响以及相关信号转导机制。方法 HUVEC-12细胞分别经不同浓度(0、20、40和80 mg/L)、不同时间(0、6、12、24和48 h)HDL3、ox-HDL3孵育,采用实时定量PCR、ELISA和免疫细胞化学法检测t-PA表达情况。用Western blot检测HDL3、ox-HDL3对Phospho-p38 MAPK、细胞核内NF-κB p65的影响。分别用p38 MAPK和NF-κB的特异性抑制剂SB203580(0.1μmol/L)和BAY11-7085来探讨HDL3、ox-HDL3影响HUVEC细胞t-PA表达的机制。结果与0 mg/L组细胞比较,ox-HDL3呈剂量和时间依赖性下调t-PAmRNA的表达,以80 mg/L浓度组减少最明显,较0 mg/L ox-HDL3下降了30%(P<0.05),其中以24 h组细胞中减少最明显,较0 h ox-HDL3组下降了19%(P<0.05);ELISA结果显示,ox-HDL3也呈剂量和时间依赖性减少了细胞培养液中t-PA的含量,以80 mg/L浓度处理组减少最明显,较0 mg/L ox-HDL3下降了34%(P<0.05),而时效以24 h组细胞中减少最明显,较0 h ox-HDL3组下降了35%(P<0.05);免疫细胞化学的结果显示,与对照组和HDL3(80 mg/L)组相比,ox-HDL3(80 mg/L)组t-PA的表达有所下降,较对照组下降了40%,而较HDL3(80 mg/L)组下降了15%(P<0.05)。与对照组和HDL3组相比、ox-HDL3(40 mg/L和80 mg/L)组Phospho-p38 MAPK的水平增加且细胞核内NF-κBp65的量也有所增加,与对照组相比ox-HDL3(80 mg/L)组Phospho-p38 MAPK的水平增加了40%,核内NF-κB p65的量增加了45%(P<0.05)。采用p38 MAPK抑制剂(SB203580)与NF-κB抑制剂(BAY11-7085)预先处理后,ox-HDL3抑制t-PAmR-NA及蛋白表达的作用有所下降,与ox-HDL3(80 mg/L)组相比,t-PA mRNA的表达分别增加了11%和13%,而t-PA蛋白表达分别增加了9%和11%(P<0.05)。结论 HDL3氧化修饰后对内皮细胞t-PA的表达具有下调作用且与p38 MAPK、NF-κB信号途径相关。

语种： 中文

作者： Mo, Zhong-Cheng;Xiao, Ji;Liu, Xie-Hong;Hu, Yan-Wei;Li, Xiao-Xu;...

期刊： Journal of Atherosclerosis and Thrombosis,2011年18(9):796-807 ISSN：1340-3478

通讯作者： Tang, Chao-Ke

作者机构： [Tang, Chao-Ke; Li, Xiao-Xu; Hu, Yan-Wei; Liu, Xie-Hong; Tang, Ya-Ling; Mo, Zhong-Cheng; Yi, Guang-Hui; Wang, Zuo; Xiao, Ji] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha, Hunan, Peoples R China.

通讯机构： [Tang, Chao-Ke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.

关键词： Advanced oxidation protein products;ATP-binding cassette transporter A1;JAK/STAT;Cholesterol efflux

摘要： AIMS: Advanced oxidation protein products (AOPPs) are new independent risk factor for coronary artery disease. This study was to determine the effects and potential mechanisms of AOPPs on cholesterol efflux from human macrophage foam cells. METHODS: Human THP-1 monocytes were preincubated with Phorbol-12-myristate- 13-acetate (PMA) and oxidized low density lipoprotein (ox-LDL) to form foam cells. The protein and mRNA expression were examined by western immunoblotting assays and real-time quantitative PCR, respectively. Cellular cholesterol content was measured by HPLC. The cholesterol efflux was assessed by liquid scintillation counting. RESULTS: AOPPs significantly decreased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1) and liver X receptor alpha (LXRalpha) and reduced cholesterol efflux from THP-1 macrophage- derived foam cells. AOPPs substantially activated NADPH oxidase and activated Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal pathway in THP-1-derived foam-like cells. Inhibiting NADPH oxidase by diphenyliodonium (DPI) effectively abolished the AOPPs-induced decrease in cholesterol efflux and the expression of ABCA1. Inhibiting JAK/STAT activation by its specific inhibitor AG-490 or by siRNA could also block AOPPs action on THP-1 cells. CONCLUSIONS: AOPPs may first down-regulate the expression of LXRalpha and ABCA1 through JAK/STAT signal pathway activation and then inhibit cholesterol efflux in THP-1-derived foam-like cells; therefore, our study may be useful for understanding the critical effects of AOPPs on the pathogenesis of atherosclerosis.

语种： 英文

作者： 李爽;张凯;王佐

期刊： 生命的化学,2011年31(6):779-784 ISSN：1000-1336

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,衡阳,421001

关键词： 内皮祖细胞;动员;影响因素;机制

摘要： 内皮祖细胞(endothelial progenitor cell, EPC)是一类最初产生于骨髓，并能定向分化为成熟血管内皮细胞的前体细胞，参与血管新生，并在血管内皮修复及维持血管内皮组织自身平衡中起关键作用。从骨髓刺激内皮祖细胞的动员，增加循环内皮祖细胞的数量，是促进血管新生及内皮修复的一种有效措施。本文就EPC动员的影响因素及其机制进行综述。

语种： 中文

作者： 张凯;李爽;许选选;王佐

期刊： 中国动脉硬化杂志,2011年19(3):210-210 ISSN：1007-3949

作者机构： [张凯; 李爽; 许选选; 王佐] 南华大学心血管疾病研究所

关键词： 脂蛋白(a);内皮型一氧化氮合酶;内皮祖细胞

摘要： 目的 研究脂蛋白(a)[Lp(a)]是否通过抑制内皮型一氧化氮合酶(eNOS)表达损伤内皮祖细胞(EPC)。方法密度梯度离心结合差速贴壁法分离出人脐静脉血EPC，在EGM-2培养基中对EPC培养和诱导分化12天后，并用免疫荧光和流式细胞术鉴定。10~9个/L EPC种植于24孔培养板上，分别与0、10、25、50及100 mg/L Lp(a)孵育24 h进行作用量-效分析，然后EPC与10 μmol/L ATP(eNOS激动剂)+50 mg/L Lp(a)处理24 h，同时设对照组。MTT法检测EPC存活率，RT-PCR和Westem blot分别检测eNOS mRNA及蛋白水平。结果 Lp(a)呈剂量依赖性降低EPC的存活率，10 mg/L Lp(a)对EPC存活率的影响不显著(P>0.05，n=3)，25 mg/L Lp(a)即表现出明显的抑制作用(P <0.05，n=3)，以50 mg/L Lp(a)最为显著(P< 0.001，n=1)；此浓度下，EPC的eNOS mRNA和蛋白水平均显著下降；10 μmol/L ATP可显著拮抗Lp(a)对EPC存活的抑制作用，同时eNOS mRNA和蛋白水平均明显上调。结论 Lp(a)损伤EPC与抑制eNOS表达有关。

语种： 中文

作者： 王佐;张凯;王仁;苏维;李爽;...

期刊： 中国动脉硬化杂志,2011年19(10):865-869 ISSN：1007-3949

作者机构： [王佐; 张凯; 王仁; 苏维; 李爽; 杨简; 姜志胜] 南华大学心血管病研究所

关键词： 内皮祖细胞;单个核细胞;兔骨髓;密度梯度离心法;差速贴壁法

摘要： 目的探索简单有效分离培养兔骨髓源性内皮祖细胞的方法，并比较两种内皮祖细胞生物学性状。方法 4周龄左右的新西兰兔，于每侧胫骨取骨髓2 mL，密度梯度离心后取单个核细胞接种于培养瓶，48 h后将悬浮的细胞收集再次贴壁，血管内皮生长因子诱导其向内皮祖细胞分化。免疫细胞化学鉴定其表面标志物、免疫荧光功能学测定，对比前后两种贴壁细胞生长状况。结果早期获取的单个核细胞，半小时后就开始贴壁，3天左右即可长出长梭形的细胞，胞体较大，有血岛样克隆形成，随后培养可形成管腔样结构，10天左右即可呈漩涡状融合整个培养瓶，但这种细胞传代能力差，为早期内皮祖细胞；第2次贴壁的晚期细胞于贴壁后呈椭圆形生长，贴壁后5 ~ 7天即可出现集落，片状生长，最后呈铺路石样融合，并可连续传至10代以上，为晚期内皮祖细胞。第2次贴壁的内皮祖细胞在分化过程中明显失去CD133~+，而CD34~+表达有所升高，大部分第1次贴壁内皮祖细胞可以吞噬乙酰化低密度脂蛋白和荆豆凝集素1，第2次贴壁内皮祖细胞功能学鉴定结果与第1次贴壁的结果类似。结论改良后的密度梯度离心法结合，差速贴壁法能有效分离培养兔骨髓源性内皮祖细胞，第2次贴壁的内皮祖细胞生长能力更强。

语种： 中文

作者： 王佐;王仁

期刊： 中国动脉硬化杂志,2011年(3):257-258 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

关键词： 脂蛋白(a);Notch信号通路;骨髓源性内皮祖细胞;血管生成

摘要： 目的研究脂蛋白(a)对兔骨髓源性内皮祖细胞血管生成的影响及其机制。方法采用密度梯度离心及差速贴壁法从新西兰白兔骨髓中分离培养内皮祖细胞(EPC)。实验共分4组:对照组、脂蛋白(a)组、Delta-like4(Dll4)(Notch信号通路激动剂)组,兴奋剂+脂蛋白(a)组。免疫荧光双抗及功能学鉴定EPC,matrigel胶血管样结构形成分析,实时定量PCR和Western blot分别检测Jag-1的mRNA和蛋白水平。结果脂蛋白(a)呈剂量依赖性对兔骨髓源性内皮祖细胞血管生成产生影响,在培养液中加入50 mg/L脂蛋白(a)24 h后,单位面积血管密度降低,单位面积血管的长度下降到50 mm/cm2,抑制血管生成37.5%+2.3%,随着脂蛋白(a)浓度的增加,损伤加重,在70 mg/L时单位面积血管的长度减少到38 mm/cm2,抑制率52.5%+2.8%,90 mg/L时达到24 mm/cm2抑制率70.0%+3.1%,低于50 mg/L时损伤变化不明显。加入Notch信号通路激动剂Dll4后,血管损伤减轻,密度增加,单位面积血管的长度在脂蛋白(a)浓度50 mg/L时由原来的50 mm/cm2恢复到72 mm/cm2,在90 mg/L血管长度时由原来的24 mm/cm2恢复到41 mm/cm2。而在Notch信号通路激动剂组,血管结构密度增加,单位面积血管样结构的长度达到120 mm/cm2,PCR和Western blot检测Jag-1的mRNA和蛋白表达增加,说明脂蛋白(a)对血管生成的影响通过Notch信号通路实现。结论脂蛋白(a)通过下调Notch信号通路抑制兔骨髓源性内皮祖细胞血管生成。

语种： 中文

作者： Zhang, Zuping;Tang, Hailin;Wang, Zeyou;Zhang, Baoxin;Liu, Wei;...

期刊： Molecular Cancer,2011年10(1):1-16 ISSN：1476-4598

通讯作者： Wu, Minghua

作者机构： [Wu, Minghua; Tang, Hailin; Zhang, Zuping; Wang, Zeyou; Lu, Hongmei; Li, Xiaoling; Liu, Wei; Xiao, Lan; Wang, Rong; Li, Guiyuan; Liu, Xiaoping] Cent S Univ, Minist Educ, Key Lab Carcinogenesis & Canc Invas, Canc Res Inst, Changsha 410078, Hunan, Peoples R China.;[Zhang, Zuping] Cent S Univ, Dept Parasitol, Changsha 410078, Hunan, Peoples R China.;[Tang, Hailin] Univ S China, Canc Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Baoxin] Armed Police Hosp Hunan Prov, Changsha 410008, Hunan, Peoples R China.;[Lu, Hongmei] Cent S Univ, Coll Chem & Chem Engn, Res Ctr Modernizat Chinese Herbal Med, Changsha 410083, Peoples R China.

通讯机构： [Wu, Minghua] C;Cent S Univ, Minist Educ, Key Lab Carcinogenesis & Canc Invas, Canc Res Inst, 110 Xiang Ya Rd, Changsha 410078, Hunan, Peoples R China.

关键词： DNA methylation;MiR-185;Glioma;DNMT1

摘要： Background: Perturbation of DNA methylation is frequent in cancers and has emerged as an important mechanism involved in tumorigenesis. To determine how DNA methylation is modified in the genome of primary glioma, we used Methyl-DNA immunoprecipitation (MeDIP) and Nimblegen CpG promoter microarrays to identify differentially DNA methylation sequences between primary glioma and normal brain tissue samples.Methods: MeDIP-chip technology was used to investigate the whole-genome differential methylation patterns in glioma and normal brain tissues. Subsequently, the promoter methylation status of eight candidate genes was validated in 40 glioma samples and 4 cell lines by Sequenom's MassARRAY system. Then, the epigenetically regulated expression of these genes and the potential mechanisms were examined by chromatin immunoprecipitation and quantitative real-time PCR.Results: A total of 524 hypermethylated and 104 hypomethylated regions were identified in glioma. Among them, 216 hypermethylated and 60 hypomethylated regions were mapped to the promoters of known genes related to a variety of important cellular processes. Eight promoter-hypermethylated genes (ANKDD1A, GAD1, HIST1H3E, PCDHA8, PCDHA13, PHOX2B, SIX3, and SST) were confirmed in primary glioma and cell lines. Aberrant promoter methylation and changed histone modifications were associated with their reduced expression in glioma. In addition, we found loss of heterozygosity (LOH) at the miR-185 locus located in the 22q11.2 in glioma and induction of miR-185 over-expression reduced global DNA methylation and induced the expression of the promoter-hypermethylated genes in glioma cells by directly targeting the DNA methyltransferases 1.Conclusion: These comprehensive data may provide new insights into the epigenetic pathogenesis of human gliomas. © 2011 Zhang et al; licensee BioMed Central Ltd.

语种： 英文

作者： Zhao, Zhan-Zhi;Wang, Zuo;Li, Guo-Hua;Wang, Ren;Tan, Jian-Miao;...

期刊： Experimental Biology and Medicine,2011年236(2):169-176 ISSN：1535-3702

通讯作者： Jiang, Zhi-Sheng

作者机构： [Jiang, Zhi-Sheng] Univ S China, Inst Cardiovasc Dis, Hengyang City 421001, Hunan, Peoples R China.;Univ S China, Key Lab Arteriosclerol Hunan Prov, Hengyang City 421001, Hunan, Peoples R China.

通讯机构： [Jiang, Zhi-Sheng] U;Univ S China, Inst Cardiovasc Dis, Hengyang City 421001, Hunan, Peoples R China.

关键词： hydrogen sulfide;foam cells;oxidized low-density lipoprotein;macrophages;scavenger receptors;acyl-coenzyme A:cholesterol acyltransferase-1

摘要： Recent evidence indicates that hydrogen sulfide (H2S) exerts an antiatherogenic effect, but the mechanism is unclear. Formation of macrophage-derived foam cells is a crucial event in the development of atherosclerosis. Thus, we explore the effect of H2S on the formation of macrophage-derived foam cells. Incubation of monocyte-derived macrophages with oxidized LDL (oxLDL) alone caused significant increases both in intracellular lipids revealed by Oil-red O staining and in intracellular total cholesterol (TC) and esterified cholesterol (EC) concentrations assessed by high-performance liquid chromatography. Sodium hydrosulfide (NaHS, an H 2S donor) remarkably abrogated oxLDL-induced intracellular lipid accumulation, and attenuated TC and EC concentrations and EC/TC ratio, whereas DL-propargylglycine (PPG) (a H2S-generating enzyme cystathionine gamma lyase inhibitor) exacerbated lipid accumulation and augmented TC and EC concentrations and EC/TC ratio. Incubation of 1,1′-dioctadecyl-3,3, 3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-oxLDL led to lipoprotein binding and uptake of macrophages, which was blunted by NaHS, but enhanced by PPG. Furthermore, OxLDL markedly induced CD36, scavenger receptor A (SR-A) and acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) expressions in macrophages, which was suppressed by NaHS (50-200 μmol/L). Finally, the down-regulations of TC and EC concentrations as well as CD36 and ACAT-1 expressions by NaHS were suppressed by glibenclamide, a KATP channel blocker, but facilitated by PD98059, an extracellular signal-regulated kinases 1 and 2 (ERK1/2) inhibitor. These results suggested that H2S inhibits foam cell formation by down-regulating CD36, SR-A and ACAT1 expressions via the KATP/ERK1/2 pathway in human monocyte-derived macrophages. Copyright © 2011 by the Society for Experimental Biology and Medicine.

语种： 英文

作者： 张晓蕾;王佐

期刊： 中国动脉硬化杂志,2011年(3):271-272 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

关键词： 氧化脂蛋白(a);人脐静脉内皮细胞;桥粒芯糖蛋白;桥粒芯胶蛋白;通透性

摘要： 目的探讨氧化脂蛋白(a)[oxLp(a)]对人脐静脉内皮细胞(HUVEC)上跨膜蛋白桥粒芯糖蛋白1(DSG1)以及桥粒芯胶蛋白(DSC2)的表达及单层内皮细胞通透性的影响。方法每次实验前6 h给HUVEC换上新鲜的无血清培养基,使细胞饥饿,6 h后再换上新鲜的培养基并加入不同浓度的oxLp(a)(0、25、50、100 mg/L)孵育HUVEC 24 h;100 mg/L oxLp(a)分别处理HU-VEC不同时间(0、6、12、24 h),RT-PCR和Western blot分别检测DSG1、DSC2 mRNA以及蛋白的表达。Transwell上种植单层HUVEC,100 mg/L oxLp(a)处理HUVEC 24 h后,于Transwell上室加入100μL1 g/L的FITC-dextran,分别在不同的时间点(0min,15 min,30 min,1 h,2 h,4 h)收集下室中的液体,用荧光分光光度计测量液体的荧光强度,确定测量通透性的最佳时间;用不同浓度的oxLp(a)(0、25、50、100 mg/L)分别或者与SOD(100 mg/L)共同孵育HUVEC 24 h后,在上室中加入FITC-dextran孵育2 h,空白组作为对照,取下室中的液体测量荧光强度。结果 oxLp(a)使HUVEC上DSG1、DSC2的表达下调,在25 mg/L时即有显著作用,且随着oxLp(a)浓度的升高,DSG1、DSC2 mRNA和蛋白表达水平呈浓度依赖的下降趋势(P<0.05);oxLp(a)孵育HUVECs 6 h即能显著地下调DSG1、DSC2的表达,且随着处理时间的延长,DSG1、DSC2 mRNA和蛋白表达水平呈时间依赖的下降趋势(P<0.05)。oxLp(a)剂量依赖性增加单层内皮细胞的通透性,100 mg/L作用最显著(P<0.05),2 h是测量通透性的最佳时间;100 mg/L oxLp(a)引起的单层内皮细胞通透性的增加能够被SOD所抑制(P<0.05)。结论 oxLp(a)呈浓度依赖性和时间依赖性的方式下调HUVECs上DSG1、DSC2的表达,并相应地增加单层内皮细胞的通透性。

语种： 中文

作者： 唐志晗;王佐;姜志胜;刘录山

期刊： 中国动脉硬化杂志,2010年18(10):787-791 ISSN：1007-3949

作者机构： [唐志晗; 王佐; 姜志胜; 刘录山] 南华大学心血管疾病研究所

关键词： 前蛋白转化酶枯草溶菌素9;半胱天冬氨酸蛋白酶3;半胱天冬氨酸蛋白酶9;细胞凋亡;生物信息学

摘要： 目的研究前蛋白转化酶枯草溶菌素9促凋亡的作用是否与活化凋亡通路Caspase-3相关.方法用80mg/L氧化型低密度脂蛋白孵育人脐静脉内皮细胞24h,同时设空白对照组,转染试剂组,阴性对照组和80nmol/L前蛋白转化酶枯草溶菌素9siRNA+80mg/L氧化型低密度脂蛋白组,流式细胞术测定细胞凋亡率,免疫印迹法和酶联免疫吸附法分别检测Caspase-3的表达及活性.然后通过生物信息学方法对前蛋白转化酶枯草溶菌素9与Caspase-8和Caspase-9进行比较,找出它们之间的序列相似程度,以及是否存在共同的功能结构域.结果前蛋白转化酶枯草溶菌素9siRNA能抑制氧化型低密度脂蛋白诱导的Caspase-3蛋白表达和活性增加.生物信息学分析表明,前蛋白转化酶枯草溶菌素9,Caspase-8,Caspase-9三者的序列同源性高达22.14%,三者在C端的二级结构十分接近,特别是前蛋白转化酶枯草溶菌素9和Caspase-9的螺旋,片层,转角,无规则卷曲含量十分接近,三级结构分析发现前蛋白转化酶枯草溶菌素9和Caspase-9的外观轮廓相近,且在腹部中央都有一个裂口,显示前蛋白转化酶枯草溶菌素9和Caspase-9可能具有相同的酶切活性.结论前蛋白转化酶枯草溶菌素9具有与Caspase-9相似的功能结构域,可能具有激活Caspase-3的功能

语种： 中文

作者： Liu, Qingnan;Dai, Zhibing;Liu, Zhiqiang;Liu, Xiaohui;Tang, Chaoke;...

期刊： 生物化学与生物物理学报,2010年42(9):635-645 ISSN：1672-9145

通讯作者： Yuan, Zhonghua

作者机构： [Tang, Chaoke; Liu, Qingnan; Jiang, Zhisheng; Yi, Guanghui; Liu, Lushan; Liu, Zhiqiang; Wang, Zuo; Liu, Xiaohui; Yang, Yongzong; Yuan, Zhonghua] Univ S China, Key Lab Arteriosclerol Hunan Prov, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.;[Dai, Zhibing] Univ S China, Inst Pathobiol, Hengyang 421001, Peoples R China.;[Liu, Qingnan] YiYang Med Coll, Dept Basic Nursing, Yiyang 413000, Peoples R China.;[Dai, Zhibing] Cent Hosp Yiyang, Dept B Type Ultrason Diag, Yiyang 413000, Peoples R China.

通讯机构： [Yuan, Zhonghua] U;Univ S China, Key Lab Arteriosclerol Hunan Prov, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.

关键词： adipophilin;ERK1;atherosclerosis;PPAR gamma

摘要： It has been reported that oxidized low-density lipoprotein (Ox-LDL) can increase the expression of adipophilin. However, the detailed mechanisms are not fully understood. The aim of this study was to investigate the mechanism of Ox-LDL on adipophilin expression and the intracellular lipid droplet accumulation. A mouse macrophage-like cell line, RAW264.7, was used throughout, and it was found that Ox-LDL induced adipophilin expression in a dose-dependent manner. Moreover, Ox-LDL induced peroxisome proliferator-activated receptor-γ (PPARγ) expression and PPARγ-specific inhibitor T0070907 abrogated Ox-LDL-induced adipophilin expression, but specific agonist GW1929 not. Furthermore, Ox-LDL induced phosphorylation of ERK1/2, and ERK1/2-specific inhibition by PD98059 suppressed the Ox-LDL-induced PPARγ and adipophilin expression. The results showed that ERK1/2 or PPARγ-specific inhibition decreased the amounts of intracellular lipid droplets. Meanwhile, the PPARγ-specific agonist increased intracellular lipid droplets. These results suggested that Ox-LDL-induced increase in adipophilin level via ERK1/2 activation is one of the mechanisms of inducing greater amounts of intracellular lipid droplets in RAW264.7 cells, which indicated that adipophilin is involved in atherosclerotic progression. © The Author 2010.

语种： 英文

作者： 赵战芝;胡艳;宋砚明;雷建军;姜志胜;...

期刊： 中国动脉硬化杂志,2010年18(10):775-778 ISSN：1007-3949

作者机构： [赵战芝; 胡艳; 宋砚明; 雷建军; 姜志胜; 王佐] 南华大学心血管疾病研究所

关键词： 大蒜素;Caco-2细胞;三磷酸腺苷结合盒转运子G5;三磷酸腺苷结合盒转运子G8;胆固醇排出

摘要： 目的 观察大蒜素对肠道细胞系Caco-2细胞胆固醇外排及胆固醇转运基因ABCG5/ABCG8表达的影响,探讨大蒜素对肠道细胞胆固醇转运的影响及机制.方法 Caco-2细胞随机分为对照组,胆固醇微胶粒组,胆固醇微胶粒加大蒜素组和大蒜素组4组.处理末,采用油红O染色观察细胞内脂滴,高效液相色谱法测细胞内胆固醇含量,免疫印迹法测ABCG5和ABCG8 的蛋白表达. 结果 与对照组比较,胆固醇微胶粒增加Caco-2细胞内脂滴和胆固醇含量(P<0.05),而大蒜素减少胆固醇微胶粒处理后细胞内脂滴和胆固醇含量,增加细胞内胆固醇排出率(70.30%比20.92%,P<0.05).大蒜素显著上调Caco-2细胞ABCG5和ABCG8的蛋白水平. 结论大蒜素促进细胞内胆固醇排出,其机制可能与上调ABCG5和ABCG8表达相关.

语种： 中文

作者： Wei, D. H.;Wang, G. X.*;Tang, C. J.;Ye, L. Q.;Huang, H.;...

期刊： IFMBE Proceedings,2010年31(2):1016-1019 ISSN：1680-0737

通讯作者： Wang, G. X.

作者机构： [Wang, G. X.; Ye, L. Q.; Wei, D. H.; Tang, C. J.; Huang, H.; Yang, L.] Chongqing Univ, Key Lab Biorheol Sci & Technol, Minist Educ, Bioengn Coll, Shazhengjie 174, Chongqing 630044, Peoples R China.;[Liu, L. S.; Wei, D. H.; Wang, Z.] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang, Peoples R China.;[Ye, L. Q.] Yangtze Normal Univ, Anal Ctr, Chongqing, Peoples R China.

通讯机构： [Wang, G. X.] C;Chongqing Univ, Key Lab Biorheol Sci & Technol, Minist Educ, Bioengn Coll, Shazhengjie 174, Chongqing 630044, Peoples R China.

会议名称： 6th World Congress of Biomechanics (WCB 2010)

会议时间： AUG 01-06, 2010

会议地点： Biomed Engn Soc Singapore, Singapore, SINGAPORE

会议主办单位： Biomed Engn Soc Singapore

会议论文集名称： IFMBE Proceedings

关键词： Atherosclerosis;Cell adhesion;Endothelium;Fluid shear stress;Low density lipoprotein

摘要： In this study, we investigated the effect of low density lipoprotein (LDL) on endothelial cell adhesion in shear stress. The endothelial cells were incubated with four different concentrations of low density lipoprotein for 24h. Thereafter, the content of cholesterol ester in endothelial cells was assayed with High Performance Liquid Chromatography (HPLC). The lipid within endothelial cells was detected with oil red O. F-actin was examined with fluorescence staining of rhodamine-phalloidin. A micropipette aspiration technique was employed to investigate the viscoelasticity of endothelial cells treated by LDL. After treated with LDL, endothelial cells were subjected to flow shear stress of 15Pa for 24h. Compared to control, LDL significantly increased the ester level in endothelial cells (p<0.05). Observation by fluorescence microscopy showed that the fibers of F-actin in normal endothelial cells concentrated along the cell membrane and no dense fibers were observed in the cytoplasm. The abnormal F-actin were appeared in LDL-treated endothelial cells, while most of the peripheral fibers disappeared and dense stress fibers were observed in the cytoplasm with high dose LDL. After exposed to 1.5 Pa shear stress the conformance and the adhesion of endothelial cells which incubated with 150 mg/L LDL decreased comparing with control. It is concluded that LDL causes lipid accumulation and the cytoplasm damaged, which may relate to endothelial cell conformance and adhesion. © 2010 International Federation for Medical and Biological Engineering.

语种： 英文

作者： Wei Dang-heng*;Wang Gui-xue;Tang Chao-jun;Liu Lu-shang;Wang Zuo;...

期刊： Proceedings of the 2009 2nd International Conference on Biomedical Engineering and Informatics, BMEI 2009,2009年:1343-+ ISSN：1948-2914

通讯作者： Wei Dang-heng

作者机构： [Liu Lu-shang; Wang Zuo; Tang Chao-ke; Wei Dang-heng] Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.;[Liu Lu-shang; Wang Zuo; Wang Gui-xue; Wei Dang-heng; Tang Chao-jun] Chongqing Univ, Bioengn Coll, Chongqing 400044, Peoples R China.;[Ruan Chang-geng; Wei Dang-heng] Suzhou Univ, Suzhou 215400, Peoples R China.

通讯机构： [Wei Dang-heng] U;Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.

关键词： low density lipoprotein;concentration polarization;stenosis;endothelial cells;adhesion

摘要： To test the hypothesis that concentration polarization of atherogenic lipids may occur in the arterial system and probe the effect of endothelial cells (ECs). A modifier with local stenosis was developed. The luminal surface LDL concentration at the distal of stenosis was analyzed with numerical stimulation and was measured by confocal microscopy. ECs were incubated with low density lipoprotein(LDL). Then, ECs were exposed to shear stress(15dyn/cm2) and F-actin was examined by fluorescence staining. Numerical stimulation showed that the luminal surface LDL concentration was higher than the bulk concentration. The relative luminal surface LDL concentration varied with the velocity and degree of stenosis. The experimental detection result was very good agreement with the numerical analysis. After treated with LDL, F-actin reorganization was observed. Under flow, the adhesion and retention of ECs were negatively relative to LDL concentration. Therefore provided concentration polarization of LDL occurs at the distal end of stenosis, and in turn effect the adhesion of ECs under flow.

语种： 英文