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Inhibiting NF-κB increases cholesterol efflux from THP-1 derived-foam cells treated with AngⅡ via up-regulating the expression of ATP-binding cassette transporter A1
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作者 Kun Liu Yanfu Wang Zhijian Chen Yuhua Liao Xiang Gao Jian Chen 《Journal of Nanjing Medical University》 2008年第4期211-216,共6页
Objective: To study the role of nuclear factor-kappa B(NF- κB) in cholesterol efflux from THP-1 derived-foam cells treated with Angiotensin Ⅱ(Ang Ⅱ ). Methods:Cultured THP-1 derived-foam cells were treated wi... Objective: To study the role of nuclear factor-kappa B(NF- κB) in cholesterol efflux from THP-1 derived-foam cells treated with Angiotensin Ⅱ(Ang Ⅱ ). Methods:Cultured THP-1 derived-foam cells were treated with Ang Ⅱ or preincubated with tosyl-phenylalanine chloromethyl-ketone(TPCK) NF- κB inhibitor. The levels of activated NF- κB in the cells were examined by sandwich ELISA, Cellular cholesterol content was studied by electron microscopy scanning and zymochemistry via fluorospectrophotometer and cholesterol effiux was detected by scintillation counting technique. ABCA1 mRNA and protein were quantified by RT-PCR and Western blotting. Results:Addition of TPCK to the cells before Ang Ⅱ stimulation attenuated the response of NF- κB p65 nuclear translocation induced by Ang Ⅱ and showed no peak in foam cells group and caused a reduction in cholesterol content and an increase in cholesterol efflux by 24.1%(P〈 0.05) and 41.1%(P〈 0.05) respectively, when compared with Ang Ⅱ group. In accordance, the ABCA1 mRNA and protein were increased by 30% and 19%(P 〈 0.05) respectively, when compared with Ang Ⅱ group. Conclusion:Ang Ⅱ can downregulate ABCA1 in THP-1 derived-foam cells via NF- K B, which leads to less cholesterol effiux and the increase of cholesterol content with the consequence of the promotion of atherosclerosis. 展开更多
关键词 Angiotensin nuclear factor- kappa b atp-binding cassette transporter A1 cholesterol effiux ATHEROSCLEROSIS
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ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10(ABCC1O) are not primary resistance factors for cabazitaxel 被引量:5
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作者 Rishil J Kathawala Yi-Jun Wang +6 位作者 Suneet Shukla Yun-Kai Zhang Saeed Alqahtani Amal Kaddoumi Suresh V Ambudkar Charles R Ashby Jr Zhe-Sheng Chen 《Chinese Journal of Cancer》 SCIE CAS CSCD 2015年第3期115-120,共6页
Introduction:ATP-binding cassette subfamily B member 1(ABCB1) and subfamily C member 10(ABCCIO) proteins are efflux transporters that couple the energy derived from ATP hydrolysis to the translocation of toxic substan... Introduction:ATP-binding cassette subfamily B member 1(ABCB1) and subfamily C member 10(ABCCIO) proteins are efflux transporters that couple the energy derived from ATP hydrolysis to the translocation of toxic substances and chemotherapeutic drugs out of cells.Cabazitaxel is a novel taxane that differs from paclitaxel by its lower affinity for ATP-binding cassette(ABC) transporters.Methods:We determined the effects of cabazitaxel,a novel tubulin-binding taxane,and paclitaxel on paclitaxelresistant,ABCB1-overexpressing KB-C2 and LLC-MDR1-WT cells and paclitaxel-resistant,ABCC10-overexpressing HEK293/ABCC10 cells by calculating the degree of drug resistance and measuring ATPase activity of the ABCB1 transporter.Results:Decreased resistance to cabazitaxel compared with paclitaxel was observed in KB-C2,LLC-MDR1-WT,and HEK293/ABCC10 cells.Moreover,cabazitaxel had low efficacy,whereas paclitaxel had high efficacy in stimulating the ATPase activity of ABCB1,indicating a direct interaction of both drugs with the transporter.Conclusion:ABCB1 and ABCC10 are not primary resistance factors for cabazitaxel compared with paclitaxel,suggesting that cabazitaxel may have a low affinity for these efflux transporters. 展开更多
关键词 ATP酶活性 阻力 家族 会员 亚科 HEK293 化疗药物 紫杉醇
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YTHDC1介导ABCB6上调诱导AD小鼠神经元细胞铁死亡促进认知功能障碍机制的实验研究
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作者 吴雅欣 赵锦华 +3 位作者 孟清琳 潘娜 刘养凤 苟英之 《现代检验医学杂志》 CAS 2024年第6期54-60,95,共8页
目的研究ATP结合盒B亚家族转运蛋白6(ATP-binding cassette subfamily B transporter 6,ABCB6)对阿尔兹海默症(Alzheimer’s disease,AD)小鼠认知功能障碍的影响及其可能的潜在调控分子机制。方法通过注射β-淀粉样蛋白(amyloidβ-prote... 目的研究ATP结合盒B亚家族转运蛋白6(ATP-binding cassette subfamily B transporter 6,ABCB6)对阿尔兹海默症(Alzheimer’s disease,AD)小鼠认知功能障碍的影响及其可能的潜在调控分子机制。方法通过注射β-淀粉样蛋白(amyloidβ-protein,Aβ)构建体内AD小鼠模型;采用水迷宫测试和Y迷宫测试评估大鼠学习与记忆能力、空间探索能力。通过神经元HT22细胞和Aβ构建体外AD细胞模型;采用RNA免疫沉淀(RNA immunoprecipitation,RIP)分析YTH结构域包含蛋白1(YTH domain containing proteins 1,YTHDC1)与ABCB6的结合关系;实时定量聚合酶链反应(qRT-PCR)检测过表达和敲低转染效率;Western blot检测YTHDC1和ABCB6蛋白,以及铁死亡相关蛋白[溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)]表达水平;CCK-8检测细胞活力;检测丙二醛(malondialdehyde,MDA)、还原型谷胱甘肽(glutathione,GSH)、活性氧(reactive oxygen species,ROS)水平及Fe^(2+)含量。结果AD小鼠海马组织及Aβ诱导的HT22细胞中ABCB6 mRNA(3.51±0.17 vs 1.02±0.01,3.45±0.21 vs 1.02±0.01)和蛋白(3.25±0.14 vs 1.01±0.01,3.14±0.16vs 1.01±0.01)水平均显著上调,差异具有统计学意义(t=-46.238,-20.349;-50.468,-23.013,均P<0.001)。敲低ABCB6显著降低AD小鼠抵达平台的时间、到达平台距离,增加小鼠自发交替率和进入新异臂次数的比值(t=27.007,11.264,24.414,19.901,均P<0.001)。敲低ABCB6促进HT22细胞增殖,抑制Aβ诱导的MDA,Fe^(2+)水平上调和GSH水平下调,减少ROS生成,促进SLC7A11和GPX4蛋白表达(t=2.883~26.122,均P<0.05)。YTHDC1蛋白通过与ABCB6 mRNA结合促进其稳定性,上调ABCB6蛋白表达。敲低YTHDC1显著降低ABCB6蛋白水平(t=18.504,P<0.001),促进HT22细胞增殖,升高GSH含量及SLC7A11和GPX4蛋白水平,降低MDA和Fe^(2+)含量,抑制ROS生成(t=4.404~14.486,均P<0.05)。敲低YTHDC1可以改善AD小鼠学习与记忆能力和空间探索能力。过表达ABCB6可逆转敲低YTHDC1对HT22细胞铁死亡和AD小鼠认知功能障碍的影响。结论YTHDC1可能通过介导ABCB6上调,诱导神经元细胞铁死亡,进而促进AD小鼠的认知功能障碍发生。 展开更多
关键词 阿尔兹海默症 YTH结构域包含蛋白1 ATP结合盒b亚家族转运蛋白6 铁死亡 认知功能障碍
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Construction and characterization of a humanized SLCO1B1 rat model with its application in evaluating the uptake of different statins
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作者 Yuanjin Zhang Junze Huang +6 位作者 Shengbo Huang Jie Liu Luyao Deng Chenmeizi Liang Yuanqing Guo Bingyi Yao Xin Wang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2024年第4期1592-1604,共13页
Organic anion-transporting polypeptides IB1(OATPIB1)plays a crucial role in the transport of statins.However,there are too few animal models related to OATPIB1,especially humanized animal models.In this study,the huma... Organic anion-transporting polypeptides IB1(OATPIB1)plays a crucial role in the transport of statins.However,there are too few animal models related to OATPIB1,especially humanized animal models.In this study,the human SLCOIB1 cDNA was inserted into the second exon of the rat Slcolb2 gene using CRISPR/Cas9 technology.Pharmacokinetic characteristics of statins were conducted in wild-type(WT),humanized OATPIB1(hOATPIB1),and OATPIB2 knockout(OATPIB2 KO)rats,respec-tively.The results showed that human OATPIB1 was successfully expressed in rat liver and exhibited transport function.Furthermore,the pharmacokinetic results revealed that OATPIB1 exhibited varying uptake levels of pivastatin,rosuvastatin,and fluvastatin,leading to different levels of exposure within the body.These results were consistent with those obtained from in vitro experiments using overexpressed cell lines.In conclusion,we established a novel humanized SLCOIBI transgenic rat model to assess the role of human OATPIB1 in the uptake of different statins.The different uptake mediated by OATPIB1 may be an important reason for the different efficacy of statins.The hOATPIB1 rat is a promising model for improving the prediction of human drug transport. 展开更多
关键词 CRISPR/Cas9 Drug transport Drug disposition Geneediting humanized rat model OATP1b1 SLCO1b1 STATINS
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High-density lipoprotein and atherosclerosis: Roles of lipid transporters 被引量:10
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作者 Yoshinari Uehara Keijiro Saku 《World Journal of Cardiology》 CAS 2014年第10期1049-1059,共11页
Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-... Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases. 展开更多
关键词 atp-binding cassette transporter atp-bind-ing cassette A1 atp-binding cassette G1 Apolipopro-tein A-I HIGH-DENSITY LIPOPROTEIN HIGH-DENSITY lipopro-tein therapy APOA-I MIMETIC peptide Reconstitutedf HIGH-DENSITY LIPOPROTEIN
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Efficacy of Shoushen granule on adenosine triphosphate binding cassette transporter A1, proprotein convertase subtilisin/kexin type 9 and toll-like receptor 4/nuclear factor kappa-B signaling pathway in ApoE-knockout mice 被引量:5
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作者 Li Shanshan Cao Hui +4 位作者 Shen Dingzhu Chen Chuan Xing Sanli Dou Fangfang Jia Qingling 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2019年第4期524-534,共11页
OBJECTIVE: To evaluate the efficacy of Shoushen granule, prepared with four Chinese medicinals, on the targeted regulation of adenosine triphosphate binding cassette transporter A1(ABCA1) through proprotein convertase... OBJECTIVE: To evaluate the efficacy of Shoushen granule, prepared with four Chinese medicinals, on the targeted regulation of adenosine triphosphate binding cassette transporter A1(ABCA1) through proprotein convertase subtilisin/kexin type 9(PCSK9) and toll-like receptor 4(TLR4)/nuclear factor kappa-B(NF-κB) signaling pathway to affect atherosclerosis(AS) in ApoE-knockout(ApoE-/-) mice.METHODS: ApoE-/-mice fed with a high-fat diet were used for AS modeling and divided into Model,Shoushen, and Atorvastatin groups. C57 BL/6 J mice at the same age and background strain were included in the Control group. Western blot and immunohistochemistry were used to measure ABCA1, PCSK9, TLR4, and NF-κB protein expression in mouse aortas. Enzyme-linked immuno sorbent assay was used to measure mouse serum tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), monocyte chemoattractant protein 1(MCP-1), and intercellular cell adhesion molecule-1(ICAM-1) expression. Serum lipid profiles and histopathology were also assessed. Shoushen granule were composed of Heshouwu(Radix Polygoni Multiflori) 15 g, Gouqizi(Fructus Lycii) 15 g, Sheng shanzha(Raw Fructus Crataegus Pinnatifidae) 10 g, and Sanqi(Radix Notoginseng) 3 g.RESULTS: ApoE-/-mice fed with a high-fat diet had notable AS lesions, with reduced ABCA1 and IL-10 levels, elevated PCSK9, TLR4, NF-κB, TNF-α, MCP-1,and ICAM-1 expression, and increased total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C) contents. With drug interventions, the areas of AS plaques were significantly reduced,the ABCA1 and IL-10 levels were increase, while the PCSK9, TLR4, NF-κB, TC, and LDL-C contents,and the TNF-α, MCP-1, and ICAM-1 expression were reduced.CONCLUSION: Shoushen granule effectively interfered with AS development by antagonizing the expression of key factors of the PCSK9 and TLR4/NF-κB signaling pathway to upregulate ABCA1 expression. 展开更多
关键词 Atherosclerosis atp-binding cassette transporters PROPROTEIN convertases TOLL-LIKE receptor 4 NF-KAPPA b Shoushen GRANULE
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Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model 被引量:4
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作者 Florian P Reiter Ralf Wimmer +10 位作者 Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk 《World Journal of Hepatology》 CAS 2016年第8期401-410,共10页
AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4... AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. 展开更多
关键词 CHOLESTASIS Primary sclerosing cholangitis The atp-binding cassette transporter b4 Liver fibrosis INTERLEUKIN-1
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Roles of sulfonylurea receptor 1 and multidrug resistance protein 1 in modulating insulin secretion in human insulinoma 被引量:1
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作者 Cheng-Jiang Li,Hua-Li Zhou,Jun Li,Hong-Tian Yao,Rong Su and Wen-Peng Li Department of Endocrinology(Li CJ,Zhou HL and Li WP),Department of Pathology,and Key Laboratory of Multi-organ Transplantation of Ministry of Public Health,First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2011年第1期88-94,共7页
BACKGROUND:Sulfonylurea receptor 1(SUR1)and multidrug resistance protein 1(MRP1)are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate ... BACKGROUND:Sulfonylurea receptor 1(SUR1)and multidrug resistance protein 1(MRP1)are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS:Fasting glucose,insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients.Insulin content,SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS:Insulinoma patients presented the typical demons-trations of Whipple’s triad.Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L,and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose.Immunohistochemistry and immunofluorescence staining showed that SUR1 increased,but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS:The hypersecretion of insulin in insulinomas might be,at least partially,due to the enrichment of SUR1. In contrast,MRP1,which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion. 展开更多
关键词 sulfonylurea receptor 1 multidrug resistance protein 1 atp-binding cassette transporters INSULINOMA insulin secretion
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Role of apolipoproteins,ABCA1 and LCAT in the biogenesis of normal and aberrant high density lipoproteins 被引量:1
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作者 Vassilis I.Zannis Shi Su Panagiotis Fotakis 《The Journal of Biomedical Research》 CAS CSCD 2017年第6期471-485,共15页
In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1(ABCA1), and lecithin: cholesterol acyltransferase(LCAT) in the formation of plasma H... In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1(ABCA1), and lecithin: cholesterol acyltransferase(LCAT) in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I(and to a lesser extent with apoE and apoA-IV) and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant prep HDL subpopulations that cannot be converted efficiently to a subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size a4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL.The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL. 展开更多
关键词 HDL biogenesis HDL phenotypes apolipoprotein A-I mutations apolipoprotein E apolipoprotein A-IV atp-binding cassette transporter A1(AbCA1
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LncRNA SNHG16 promotes colorectal cancer proliferation by regulating ABCB1 expression through sponging miR-214-3p 被引量:1
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作者 Pei Tan Mu Xu +5 位作者 Junjie Nie Jian Qin Xiangxiang Liu Huiling Sun Shukui Wang Yuqin Pan 《The Journal of Biomedical Research》 CAS CSCD 2022年第4期231-241,共11页
Mounting evidence indicates that long non-coding RNAs(lncRNAs)have critical roles in colorectal cancer(CRC)progression,providing many potential diagnostic biomarkers,prognostic biomarkers,and treatment targets.Here,we... Mounting evidence indicates that long non-coding RNAs(lncRNAs)have critical roles in colorectal cancer(CRC)progression,providing many potential diagnostic biomarkers,prognostic biomarkers,and treatment targets.Here,we sought to investigate the role and underlying regulatory mechanism of lncRNA small nucleolar RNA host gene 16(SNHG16)in CRC.The expressions of SNHG16 in CRC were identified by RNA-sequencing and quantitative reverse transcription PCR.The functions of SNHG16 were explored by a series of in vitro and in vivo assays(colony formation assay,flow cytometry assay,and xenograft model).Bioinformatics analysis,RNA fluorescence in situ hybridization and luciferase reporter assay were used to investigate the regulatory mechanism of effects of SNHG16.SNHG16 was found to be significantly elevated in human CRC tissues and cell lines.Functional studies suggested that SNHG16 promoted CRC cell growth both in vitro and in vivo.Mechanistically,we identified that SNHG16 is expressed predominantly in the cytoplasm.SNHG16 could interact with miR-214-3p and up-regulated its target ABCB1.This study indicated that SNHG16 plays an oncogenic role in CRC,suggesting it could be a novel biomarker and therapeutic target in CRC. 展开更多
关键词 SNHG16 atp-binding cassette subfamily b member 1 microRNA colorectal cancer ceRNA
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High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival
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作者 Bin Xi Fang-Zhou Luo +4 位作者 Bin He Fang Wang Ze-Kuan Li Ming-Chun Lai Shu-Sen Zheng 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2022年第4期370-377,共8页
Background:ATP-binding cassette transporter G1(ABCG1)regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity.But,for hepatocellular carcinoma(HCC),the role of ABCG1 has not been inves... Background:ATP-binding cassette transporter G1(ABCG1)regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity.But,for hepatocellular carcinoma(HCC),the role of ABCG1 has not been investigated.Thus,the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC.Methods:One hundred and four adult patients with HCC were enrolled,and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry.All these patients were stratified by ABCG1 expression,Kaplan-Meier analysis was used to compare the overall survival(OS)and recurrence-free survival(RFS),and Cox regression analysis was used to determine independent predictors of tumor recurrence.Results:Upregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues.Patients with high nuclear ABCG1 expression had lower OS and RFS(P=0.012 and P=0.020,respectively).High nuclear ABCG1 expression was related to larger tumor size(P=0.004)and tumor recurrence(P=0.027).Although ABCG1 was expressed in the cytoplasm,cytosolic expression could not predict the outcome in patients with HCC.A new stratification pattern was established based on the heterogenous ABCG1 expression pattern:high risk(High^(nucleus)/Low^(cytosol)),moderate risk(High^(nucleus)/High^(cytosol) or Low^(nucleus)/Low^(cytosol)),and low risk(Low^(nucleus)/High^(cytosol)).This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with HCC.Multivariate Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS(P=0.015).Conclusions:High nuclear ABCG1 expression indicates poor prognosis in patients with HCC.Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence. 展开更多
关键词 atp-binding cassette transporter G1 Hepatocellular carcinoma Overall survival Prognostic factor Progression-free survival
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Protective Effect of Irbesartan on ATP Binding Cassette Transporter A1 in THP-1 Derived Macrophages
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作者 张慧玲 李清贤 +1 位作者 王彦富 石胜伟 《South China Journal of Cardiology》 2009年第4期227-233,共7页
Objectives To explore the protective effect of irbesartan (lrb) under the interference with angiotensin II (Ang II) on ABCA1. Methods Electron microscopy was used to detect the morphous of foam cells. The expressi... Objectives To explore the protective effect of irbesartan (lrb) under the interference with angiotensin II (Ang II) on ABCA1. Methods Electron microscopy was used to detect the morphous of foam cells. The expression of ABCA1 mRNA and its protein were determined by RT-PCR and Western blotting, respectively. The variance of cellular cholesterol content was measured by zymochemistry via-fluorospeetrophotometer. Results A positive facilitative effect of Ang II on the formation of foam cells was observed. Total cholesterol was increased significantly by Ang II, the expression of ABCA1 was down-regulated obviously by Ang II; Irb could protect ABCA1 against the lesion of Ang II; Total cellular cholesterol content was reduced significantly in Irb + Ang II group; However, considerable alteration about the cholesterol content and the expression of ABCA1 were not observed in Irb group without incubation with Ang II. Conclusions Irb could protect ABCA1 against the lesion of Ang II, which may contribute to its anti-atherosclerotic properties. ( S Chin J Cardiol 2009; 10(4) : 227 -233) 展开更多
关键词 ATHEROSCLEROSIS angiotensin II IRbESARTAN atp-binding cassette transporter A1
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Two pyrrole acids isolated from Phyllanthus emblica L.and their bioactivities
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作者 Shu-Hui Wang Cong Guo +8 位作者 Wen-Jin Cui Qing-Xia Xu Jun Zhang Jin-Zhu Jiang Yan Liu Sha Chen Chang Chen Jin-Tang Cheng An Liu 《Natural Products and Bioprospecting》 CSCD 2023年第1期493-501,共9页
An undescribed pyrrole acid,1-(4′-methoxy-4′-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid(1)and one known pyr-role acid(2)were isolated from the fruits of Phyllanthus emblica.The structures of these compounds were el... An undescribed pyrrole acid,1-(4′-methoxy-4′-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid(1)and one known pyr-role acid(2)were isolated from the fruits of Phyllanthus emblica.The structures of these compounds were elucidated via the comprehensive analyses of IR,HRESIMS,1D and 2D spectroscopic data.A series of biological assays revealed that compounds 1 and 2 could inhibit LPS-induced over-production of nitric oxide(NO),interleukin-6(IL-6),monocyte chemotactic protein 1(MCP-1)and tumor necrosis factor-α(TNF-α)by reducing the phosphorylation of extracellular regulated protein kinases(ERK)and c-Jun N-terminal kinases(JNK)in RAW 264.7 cells.Additionally,compounds 1 and 2 were found to reduce lipid deposition and increase the mRNA expression of ATP-binding cassette transporter A1 in oxidized low-density lipoprotein-treated RAW264.7 macrophages. 展开更多
关键词 Pyrrole acid Phyllanthus emblica L. Lipid deposition atp-binding cassette transporter A1 RAW264.7 macrophages
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血管紧张素(1-7)和血管紧张素Ⅱ对THP-1源性泡沫细胞胆固醇外流的影响 被引量:5
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作者 柴婵娟 杨慧宇 +4 位作者 杨志明 梁斌 阎丰 武瑞 边云飞 《中国动脉硬化杂志》 CAS CSCD 北大核心 2014年第9期885-890,共6页
目的观察血管紧张素(1-7)[Ang(1-7)]及血管紧张素Ⅱ(AngⅡ)对THP-1源性泡沫细胞B族Ⅰ型清道夫受体(SR-BⅠ)、ATP结合盒转运体A1(ABCA1)表达及胆固醇外流的影响。方法将THP-1单核细胞加入100 nmol/L佛波酯(PMA)48 h诱导分化为THP-1源性... 目的观察血管紧张素(1-7)[Ang(1-7)]及血管紧张素Ⅱ(AngⅡ)对THP-1源性泡沫细胞B族Ⅰ型清道夫受体(SR-BⅠ)、ATP结合盒转运体A1(ABCA1)表达及胆固醇外流的影响。方法将THP-1单核细胞加入100 nmol/L佛波酯(PMA)48 h诱导分化为THP-1源性巨噬细胞,加入氧化型低密度脂蛋白(ox-LDL)建立泡沫细胞模型。随机分为五组:空白对照组、AngⅡ组、Ang(1-7)组、Ang(1-7)+AngⅡ组及AngⅡ+Ang(1-7)+A-779组[A-779为Ang(1-7)受体特异性阻滞剂]。分别运用RT-PCR及Western blot方法检测SR-BⅠmRNA、ABCA1mRNA及其蛋白的表达,用液体闪烁计数仪检测胆固醇流出率的变化。结果与空白对照组相比,加用AngⅡ组SR-BⅠmRNA、ABCA1mRNA及其蛋白的表达均明显减弱且胆固醇外流减少(P<0.05);与AngⅡ组比较,加用Ang(1-7)促进SR-BⅠmRNA、ABCA1mRNA及其蛋白的表达,胆固醇外流增加(P<0.05);与AngⅡ+Ang(1-7)组比较,AngⅡ+Ang(1-7)+A-779组SR-BⅠmRNA、ABCA1mRNA及其蛋白的表达减弱、胆固醇外流减少(P<0.05),但与AngⅡ组比较差异无统计学意义(P>0.05)。结论 AngⅡ抑制THP-1源性泡沫细胞SR-BⅠ、ABCA1的表达并减少胆固醇外流,而Ang(1-7)通过其特异性受体MAS受体可减弱AngⅡ的作用,促进胆固醇外流,从而对动脉粥样硬化的进展起到抑制作用。 展开更多
关键词 血管紧张素(1-7) 血管紧张素Ⅱ b族Ⅰ型清道夫受体 ATP结合盒转运体A1 胆固醇逆转运
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阿托伐他汀抑制THP-1经PMA诱导后变成巨噬细胞ATP结合盒转运子A1mRNA和蛋白的表达 被引量:1
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作者 王秀萍 容春莉 +3 位作者 于薇 李如意 彭应心 齐晓勇 《基础医学与临床》 CSCD 北大核心 2007年第3期310-313,共4页
目的探讨阿托伐他汀对THP-1巨噬细胞ATP结合盒转运子A1(ABCA1)mRNA和蛋白及LXRαmRNA表达的影响。方法体外培养的人THP-1单核细胞,经氟波酯(PMA)诱导48 h,使形成巨噬细胞,将分化良好的巨噬细胞分别加入含不同浓度或不含阿托伐他汀的无血... 目的探讨阿托伐他汀对THP-1巨噬细胞ATP结合盒转运子A1(ABCA1)mRNA和蛋白及LXRαmRNA表达的影响。方法体外培养的人THP-1单核细胞,经氟波酯(PMA)诱导48 h,使形成巨噬细胞,将分化良好的巨噬细胞分别加入含不同浓度或不含阿托伐他汀的无血清RPMI 1640培养基,培养24 h或48 h,收集细胞。用多聚酶链反应(RT-PCR)和免疫组化法检测THP-1巨噬细胞ABCA1 mRNA和蛋白及LXRαmRNA的表达。结果含阿托伐他汀(10μmol/L)的培养基体外培养人THP-1巨噬细胞24 h,ABCA1(相对表达量IA值1.21,对照组1.48)和LXRαmRNA(A值0.87,对照组1.12)表达比对照组明显减少(P<0.05),延长培养时间,ABCA1和LXRαmRNA表达有进一步减少趋势。结论阿托伐他汀抑制体外培养的人THP-1巨噬细胞ABCA1 mRNA和蛋白及LXRαmRNA的表达。 展开更多
关键词 人THP-1单核细胞 ATP结合盒转运子A1 肝X受体Α
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New insights into renal lipid dysmetabolism in diabetic kidney disease 被引量:6
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作者 Alla Mitrofanova George Burke +1 位作者 Sandra Merscher Alessia Fornoni 《World Journal of Diabetes》 SCIE 2021年第5期524-540,共17页
Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests tha... Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests that impaired cholesterol metabolism,increased lipid uptake or synthesis,increased fatty acid oxidation,lipid droplet accumulation and an imbalance in biologically active sphingolipids(such as ceramide,ceramide-1-phosphate and sphingosine-1-phosphate)contribute to the development of diabetic kidney disease(DKD).Currently,the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production,oxidative stress,inflammation,or cell death.Therefore,control of renal lipid dysmetabolism is a very important therapeutic goal,which needs to be archived.This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD. 展开更多
关键词 Diabetes LIPIDS Free fatty acids atp-binding cassette transporters sub-class A Sterol-O-acyltransferase 1 CD36 SPHINGOLIPIDS Sphingomyelin phosphodiesterase acid-like 3b Diabetic kidney disease
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Mitochondrial function and regulation of macrophage sterol metabolism and inflammatory responses 被引量:9
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作者 Annette Graham Anne-Marie Allen 《World Journal of Cardiology》 CAS 2015年第5期277-286,共10页
The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activator... The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activators of liver X receptors(LXRs),via sterol 27-hydroxylase,is regulated by the rate of flux of cholesterolto the inner mitochondrial membrane,via a complex of cholesterol trafficking proteins.Oxysterols are key signalling molecules,regulating the transcriptional activity of LXRs which coordinate macrophage sterol metabolism and cytokine production,key features influencing the impact of these cells within atherosclerotic lesions.The precise identity of the complex of proteins mediating mitochondrial cholesterol trafficking in macrophages remains a matter of debate,but may include steroidogenic acute regulatory protein and translocator protein.There is clear evidence that targeting either of these proteins enhances removal of cholesterol via LXRα-dependent induction of ATP binding cassette transporters(ABCA1,ABCG1) and limits the production of inflammatory cytokines; interventions which influence mitochondrial structure and bioenergetics also impact on removal of cholesterol from macrophages.Thus,molecules which can sustain or improve mitochondrial structure,the function of the electron transport chain,or increase the activity of components of the protein complex involved in cholesterol transfer,may therefore have utility in limiting or regressing atheroma development,reducing the incidence of coronary heart disease and myocardial infarction. 展开更多
关键词 Atherosclerosis MACROPHAGE Cholesterol High density LIPOPROTEINS APOLIPOPROTEINS ATP binding cassette transporters SCAVENGER receptor b1 Mitochondria(dys)function STEROL 27-hydroxylase Liver X receptors
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Hepatocellular transport proteins and their role in liver disease 被引量:2
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作者 Carmen Stanca Diana Jung +1 位作者 Peter J.Meier Gerd A.Kullak-Ublick 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第2期157-169,共13页
MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte... MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte cultures and basolateral plasma membrane vesicles [2,4]. 展开更多
关键词 atp-binding cassette transporters ANIMALS Carrier Proteins HEPATOCYTES humans LIVER Liver Diseases Organic Anion transporters Organic Cation transport Proteins Research Support Non-U.S. Gov't
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A Possible Mechanism Linking Hyperglycemia and Reduced High-density Lipoprotein Cholesterol Levels in Diabetes
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作者 高峰 严同 +2 位作者 赵艳 尹凡 胡翠宁 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2010年第3期318-321,共4页
This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol(HDL-C).Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco’s modified Eagle’s medium(D... This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol(HDL-C).Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco’s modified Eagle’s medium(DMEM) containing glucose of various concentrations.The cells were divided into 3 groups in terms of different glucose concentrations in the cultures:Control group(5.6 mmol/L glucose),high glucose concentration groups(16.7 mmol/L and 30 mmol/L glucose).ATP-binding cassette transporter A1(ABCA1) mRNA expression in the macrophages was detected by semi-quantitative RT-PCR 24,48 and 72 h after glucose treatment.The results showed that ABCA1 mRNA expression in the 16.7 mmol/L glucose group was not significantly different from that in the control group at all testing time points(P>0.05 for each).In the 30 mmol/L glucose group,macrophage ABCA1 mRNA expression was not changed significantly at 24 h(P=0.14),but was substantially decreased by 40.4% at 48 h(P=0.009) and by 48.1% at 72 h(P=0.015) as compared with that in the control group.It was concluded that ABCA1 is of vital importance for HDL-C biogenesis.High glucose may hamper HDL-C biogenesis by decreasing ABCA1 expression,which contributes to low HDL-C level in diabetes. 展开更多
关键词 reverse cholesterol transport DIAbETES high-density lipoprotein cholesterol atp-binding cassette transporter A1
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1-苯基2-硫脲对Tg(abcb4:eGFP)斑马鱼肿瘤多重耐药相关基因表达的影响
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作者 孔鹏 莫大双 +5 位作者 陈敏 黄江涛 安丽娟 尹正昊 舒莉萍 何志旭 《贵州医科大学学报》 CAS 2024年第11期1587-1592,1600,共7页
目的探讨去色素药物1-苯基2-硫脲(PTU)对Tg(abcb4:eGFP)斑马鱼肿瘤多重耐药相关基因abcb4及其标记基因egfp表达的影响及可能机制。方法选取受精后24 h(24 hpf)Tg(abcb4:eGFP)斑马鱼胚胎做药物暴露实验,分为Control、PTU以及PTU+RES 3个... 目的探讨去色素药物1-苯基2-硫脲(PTU)对Tg(abcb4:eGFP)斑马鱼肿瘤多重耐药相关基因abcb4及其标记基因egfp表达的影响及可能机制。方法选取受精后24 h(24 hpf)Tg(abcb4:eGFP)斑马鱼胚胎做药物暴露实验,分为Control、PTU以及PTU+RES 3个组;持续用药96 h,通过荧光显微镜拍照检测各组斑马鱼胃肠道荧光强度;RT-qPCR检测abcb4、egfp及pxr基因mRNA,Western Blot检测abcb4、egfp蛋白(Abcb4、eGFP)的表达,罗丹明B积累实验检测不同组Abcb4功能。结果与Control组相比,PTU组Tg(abcb4:eGFP)斑马鱼荧光表达增强(P<0.01),PTU+RES组荧光变化不明显(P>0.05);PTU组abcb4、egfp及pxr基因mRNA表达均增加(P<0.005),PTU+RES组pxr基因mRNA表达增加(P<0.005),abcb4、egfp基因mRNA表达无明显变化(P>0.05);PTU组abcb4、egfp蛋白表达均增加(P<0.005),PTU+RES组无明显变化(P>0.05);PTU组Abcb4功能增强(P<0.01),PTU+RES组无明显变化(P>0.05)。结论PTU可诱导Tg(abcb4:eGFP)斑马鱼abcb4和egfp表达增加,核因子pxr可能参与PTU对abcb4和egfp的诱导调节过程,在应用PTU去色素处理的Tg(abcb4:eGFP)斑马鱼进行药物筛选时需注意PTU对abcb4和egfp表达的影响。 展开更多
关键词 1-苯基2-硫脲 转基因斑马鱼 斑马鱼b4型ATP结合盒 b1型ATP结合盒 孕烷X受体 增强型绿色荧光蛋白
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