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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 transporters in progression and clinical outcome of pancreatic cancer: what is the way forward? 被引量:5
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作者 Aleksandra Adamska Marco Falasca 《World Journal of Gastroenterology》 SCIE CAS 2018年第29期3222-3238,共17页
Pancreatic ductal adenocarcinoma(PDAC) is one of the most aggressive diseases and is characterized by high chemoresistance, leading to the lack of effective therapeutic approaches and grim prognosis. Despite increasin... Pancreatic ductal adenocarcinoma(PDAC) is one of the most aggressive diseases and is characterized by high chemoresistance, leading to the lack of effective therapeutic approaches and grim prognosis. Despite increasing understanding of the mechanisms of chemoresistance in cancer and the role of ATPbinding cassette(ABC) transporters in this resistance, the therapeutic potential of their pharmacological inhibition has not been successfully exploited yet. In spite of the discovery of potent pharmacological modulators of ABC transporters, the results obtained in clinical trials have been so far disappointing, with high toxicity levels impairing their successful administration to the patients. Critically, although ABC transporters have been mostly studied for their involvement in development of multidrug resistance(MDR), in recent years the contribution of ABC transporters to cancer initiation and progression has emerged as an important area of research, the understanding of which could significantly influence the development of more specific and efficient therapies. In this review, we explore the role of ABC transporters in the development and progression of malignancies, with focus on PDAC. Their established involvement in development of MDR will be also presented. Moreover, an emerging role for ABC transporters as prognostic tools for patients' survival will be discussed, demonstrating the therapeutic potential of ABC transporters in cancer therapy. 展开更多
关键词 PANCREATIC DUCTAL ADENOCARCINOMA MULTIDRUG resistance atp-binding cassette transporters Targeted therapies PANCREATIC DUCTAL ADENOCARCINOMA prognosis Predictive markers
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Crosslink among cyclin-dependent kinase 9,ATP binding cassette transporter G2 and Beclin 1 in colorectal cancer
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作者 Zhong-Bao Shao Ke He +1 位作者 Yu-Bin Su Zhi Shi 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第12期4778-4781,共4页
Colorectal cancer(CRC)ranks third in the number of cancers mainly because of the inability to diagnose it at an early stage.The pathogenesis of CRC is complicated,which is the result of the complex interaction of mult... Colorectal cancer(CRC)ranks third in the number of cancers mainly because of the inability to diagnose it at an early stage.The pathogenesis of CRC is complicated,which is the result of the complex interaction of multiple genetic and environmental factors.Currently,one of the main treatments for CRC is chemotherapy.But the primary cause of CRC treatment failure is drug resistance.The expression of cyclin-dependent kinase 9(CDK9)was correlated with elevated autophagy levels in colon cancer,and high expression of CDK9 indicates a poor prognosis in CRC.The incidence of autophagy and the expressions of Beclin 1 and ATP binding cassette transporter G2 are different in left and right colon cancer,and autophagy may be involved in the occurrence of chemotherapy resistance.In this article,the roles of CDK9,ATP binding cassette transporter G2 and Beclin 1 in CRC were elucidated,emphasizing the linkages among them and providing potential therapeutic targets of CRC. 展开更多
关键词 Cyclin-dependent kinase 9 ATP binding cassette transporter G2 Beclin 1 Colorectal cancer CHEMOTHERAPY
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ATP-binding cassette transporter enhances tolerance to DDT in Tetrahymena 被引量:3
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作者 NING YingZhi DANG Huai +4 位作者 LIU GuangLong XIONG Jie YUAN DongXia FENG LiFang MIAO Wei 《Science China(Life Sciences)》 SCIE CAS CSCD 2015年第3期297-304,共8页
The reuse of dichlorodiphenyltrichloroethane(DDT) as an indoor residual spray was permitted by the World Health Organization in 2007, and approximately 14 countries still use DDT to control disease vectors. The extens... The reuse of dichlorodiphenyltrichloroethane(DDT) as an indoor residual spray was permitted by the World Health Organization in 2007, and approximately 14 countries still use DDT to control disease vectors. The extensive exposure of insects to DDT has resulted in the emergence of DDT resistance, especially in mosquitoes, and the mechanism for this resistance in mosquitoes has been widely reported. Spraying can also introduce DDT directly into surface water, and DDT can subsequently accumulate in microorganisms, but the mechanism for the resistance to DDT degradation in microorganisms is unclear. Using whole-genome microarray analysis, we detected an abcb15 gene that was up-regulated in a specific manner by DDT treatment in T. thermophile. The deduced ABCB15 peptide sequence had two transmembrane domains(TMDs) and two nucleotide-binding domains(NBDs) to form the structure TMD-NBD-TMD-NBD, and each NBD contained three conserved motifs: Walker-A, C-loop, and Walker-B, which indicated the T. thermophila abcb15 was a typical ABC transporter gene. The expression of ABCB15 fused with a C-terminal green fluorescent protein was found to be on the periphery of the cell, suggesting that ABCB15 was a membrane pump protein. In addition, cells with abcb15 partially knocked down(abcb15-KD) grew slower than wild-type cells in the presence of 256 mg L-1 DDT, indicating the tolerance of abcb15-KD strain to DDT exposure was decreased. Thus, we suggest that in Tetrahymena, the membrane pump protein encoded by ABCT gene abcb15 can enhance the tolerance to DDT and protect cells from this exogenous toxin by efficiently pumping it to the extracellular space. 展开更多
关键词 TETRAHYMENA DDT atp-binding cassette transporter TOLERANCE
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Overexpression of the steroidogenic acute regulatory protein increases the expression of ATP-binding cassette transporters in microvascular endothelial cells(bEnd.3)
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作者 Yan-xia NING Shun-lin REN +1 位作者 Feng-di ZHAO Lian-hua YIN 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2010年第5期350-356,共7页
Objective:To determine the effect of steroidogenic acute regulatory protein(StAR) overexpression on the levels of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1) and ATP-binding cassette transporter... Objective:To determine the effect of steroidogenic acute regulatory protein(StAR) overexpression on the levels of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1) and ATP-binding cassette transporter G1(ABCG1) in an endothelial cell line(bEnd.3).Methods:The StAR gene was induced in bEnd.3 cells with adenovirus infection.The infection efficiency was detected by fluorescence activated cell sorter(FACS) and fluorescence microscopy.The expressions of StAR gene and protein levels were detected by real-time polymerase chain reaction(PCR) and Western blot.The gene and protein levels of ABCA1 and ABCG1 were detected by real-time PCR and Western blot after StAR overexpression.Results:The result shows that StAR was successfully overexpressed in bEnd.3 cells by adenovirus infection.The mRNA and protein expressions of ABCA1 and ABCG1 were greatly increased by StAR overexpression in bEnd.3 cells.Conclusion:Overexpression of StAR increases ABCA1 and ABCG1 expressions in endothelial cells. 展开更多
关键词 Steroidogenic acute regulatory protein(StAR) Endothelial cells Cholesterol Adenosine triphosphate (ATP)-binding cassette transporter A(ABCA) atp-binding cassette transporter G(ABCG) bEnd. Steroidogenic acute regulatory protein(StAR) Endothelial cells Cholesterol Adenosine triphosphate (ATP)-binding cassette transporter A(ABCA) atp-binding cassette transporter G(ABCG) bEnd.
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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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ZBM30 suppresses atherosclerosis through up-regulating ATP-binding cassette A1 and G1
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《中国药理学通报》 CAS CSCD 北大核心 2015年第B11期47-47,共1页
Atherosclerosis is the most common cause of cardiovascular diseases, such as myocardial infarction and stroke. The aim of this study was to investigate the effects of a novel compound ZBM30 on atherosclerosis in ApoE-... Atherosclerosis is the most common cause of cardiovascular diseases, such as myocardial infarction and stroke. The aim of this study was to investigate the effects of a novel compound ZBM30 on atherosclerosis in ApoE- deficient mice and its associated mechanism. ApoE-deficient mice (6 weeks old), fed an atherogenic high-fat and high cholesterol diet for 8 weeks, were divided into three groups. Two groups were orally administrated ZBM30 (10, 30 nag ~ kg-1) daily for 12 weeks, while the control group was administered saline. Atherosclerotic lesions with en face aortas were evaluated by Sudan IV staining, and lesion areas in aortic sinuses were evaluated by oil red O staining. Necrotic core areas and fibrous cap areas in the lesion were evaluated by henaatoxylin and eosin (HE) staining and Masson' s trichronae staining in the aorta sinuses. The effects of ZBM30 on cholesterol accumulation in naacrophages and cholesterol transporters: ATP binding cassette A1 (ABCA1) and ATP binding cassette G1 (AB- CG1) were evaluated by oil red O assay, 3H-cholesterol efflux assay, Western blot, and real-time PCR on macro- phage cell lines: Raw 264.7 and THP-1. Inanauno-fluoresces was used to determine the ABCA1 expression in naac- rophage in aorta sinuses. Luciferase reporters of wild type and mutant types of ABCA1 promoter were constructed to determine the regulatory domain of ZBM30 on ABCA1 promoter. Results showed that, compared with the control group, en face lesions in ZBM30 group ( 10, 30 mg · kg^-1 ) were reduced 54.96 ± 10.06% and 71.50 ± 15.37% respectively, and aorta sinus lesions were reduced 41.85 ± 11.21% and 82.23 ± 8.25% respectively. Necrotic core areas in the ZBM30 group were markedly reduced and fibrous cap areas were not changed. Oil red O staining and 3 H-cholesterol efflux assays on Raw 264.7 cell line revealed that ZBM30 significantly attenuated the cholesterol accumulation in naacrophages by enhancing apolipoprotein AI and HDL mediated cholesterol efflux. Furthermore, ZBM30 induced the protein and naRNA expression of cholesterol transporters such as ABCA1 and ABCG1. Inanauno- fluoresces experiment revealed that ZBM30 induced the ABCA1 expression in naacrophage in the lesion, which is consistent with the results in vitro. Luciferase reporter assay revealed that ZBM30 exerted its effect on ABCA1 via liver X receptor (LXR) binding domain. In conclusion, ZBM30 suppresses atherosclerosis through up-regulating cholesterol efflux via ABCA1 and ABCG1 transporters in ApoE-deficient mice. 展开更多
关键词 ATHEROSCLEROSIS macrophage cholesterol EFFLUX atp-binding cassette A1 atp-binding cassette G1 Liver X receptor
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Coarse-Grained Free-Energy Simulations of Conformational State Transitions in an Adenosine 5′-Triphosphate-binding Cassette Exporter 被引量:1
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作者 Yun Huang Hao-chen Xu Jie-lou Liao 《Chinese Journal of Chemical Physics》 SCIE CAS CSCD 2020年第6期712-716,I0002,共6页
ATP-binding cassette exporters transport many substrates out of cellular membranes via alternating between inward-facing and outward-facing conformations. Despite extensive research efforts over the past decades, unde... ATP-binding cassette exporters transport many substrates out of cellular membranes via alternating between inward-facing and outward-facing conformations. Despite extensive research efforts over the past decades, understanding of the molecular mechanism remains elusive. As these large-scale conformational movements are global and collective, we have previously performed extensive coarse-grained molecular dynamics simulations of the potential of mean force along the conformational transition pathway [J. Phys. Chem. B 119, 1295(2015)]. However, the occluded conformational state, in which both the internal and external gate are closed, was not determined in the calculated free energy profile. In this work, we extend the above methods to the calculation of the free energy profile along the reaction coordinate, d1-d2, which are the COM distances between the two sides of the internal(d1)and the external gate(d2). The potential of mean force is thus obtained to identify the transition pathway, along which several outward-facing, inward-facing, and occluded state structures are predicted in good agreement with structural experiments. Our coarse-grained molecular dynamics free-energy simulations demonstrate that the internal gate is closed before the external gate is open during the inward-facing to outward-facing transition and vice versa during the inward-facing to outward-facing transition. Our results capture the unidirectional feature of substrate translocation via the exporter, which is functionally important in biology. This finding is different from the previous result, in which both the internal and external gates are open reported in an X-ray experiment [Proc. Natl. Acad. Sci. USA 104,19005(2007)]. Our study sheds light on the molecular mechanism of the state transitions in an ATP-binding cassette exporter. 展开更多
关键词 atp-binding cassette exporter Conformational state transition Coarse-grained molecular dynamics Potential of mean force
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How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance? 被引量:5
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作者 Adrian C.Jaramillo Farah Al Saig +2 位作者 Jacqueline Cloos Gerrit Jansen Godefridus J.Peters 《Cancer Drug Resistance》 2018年第1期6-29,共24页
P-glycoprotein(ABCB1),multidrug resistance protein-1(ABCC1)and breast cancer resistance protein(ABCG2)belong to the ATP-binding cassette(ABC)superfamily of proteins that play an important physiological role in protect... P-glycoprotein(ABCB1),multidrug resistance protein-1(ABCC1)and breast cancer resistance protein(ABCG2)belong to the ATP-binding cassette(ABC)superfamily of proteins that play an important physiological role in protection of the body from toxic xenobiotics and endogenous metabolites.Beyond this,these transporters determine the toxicity profile of many drugs,and confer multidrug resistance(MDR)in cancer cells associated with a poor treatment outcome of cancer patients.It has long been hypothesized that inhibition of ABC drug efflux transporters will increase drug accumulation and thereby overcome MDR,but until now no approved inhibitor of these transporters is available in the clinic.In this review we present molecular strategies to overcome this type of drug resistance and discuss for each of these strategies their promising value or indicate underlying reasons for their limited success. 展开更多
关键词 Breast cancer resistance protein atp-binding cassette transporters multidrug resistance multidrug resistance protein
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肾移植患者ABCA1及GPIHBP1水平与术后血脂的相关性
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作者 刘磊 丰贵文 +3 位作者 庞新路 王军祥 王志强 王志刚 《海南医学》 CAS 2024年第17期2492-2496,共5页
目的分析尿毒症肾移植患者三磷酸腺苷结合盒亚家族A成员1(ABCA1)及糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(GPIHBP1)水平与术后血脂的相关性。方法回顾性分析2015年3月至2023年1月郑州大学第一附属医院肾移植科收治的97例尿毒症肾移... 目的分析尿毒症肾移植患者三磷酸腺苷结合盒亚家族A成员1(ABCA1)及糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(GPIHBP1)水平与术后血脂的相关性。方法回顾性分析2015年3月至2023年1月郑州大学第一附属医院肾移植科收治的97例尿毒症肾移植患者的临床资料,按照术后血脂情况分为血脂正常组(n=34)和血脂紊乱组(n=63),比较两组患者术后1个月、3个月、6个月、12个月的ABCA1、GPIHBP1、血脂(高密度脂蛋白胆固醇、低密度脂蛋白、甘油三酯及总胆固醇)水平和他克莫司血药浓度,采用Pearson相关分析法分析术后ABCA1及GPIHBP1与血脂水平及他克莫司血药浓度的相关性,并比较两组患者随访12个月内并发症的发生情况。结果血脂紊乱组患者术后1个月、3个月、6个月、12个月的ABCA1、GPIHBP1、总胆固醇、甘油三酯、低密度脂蛋白胆固醇及他克莫司血药浓度明显高于血脂正常组,差异均有统计学意义(P<0.05);血脂紊乱组患者术后1个月、3个月、6个月及12个月的高密度脂蛋白胆固醇为(1.05±0.14)mmol/L、(1.14±0.18)mmol/L、(1.18±0.16)mmol/L、(1.23±0.17)mmol/L,均低于同时间段血脂正常组的(1.17±0.21)mmol/L、(1.37±0.28)mmol/L、(1.42±0.24)mmol/L、(1.50±0.32)mmol/L,差异均有统计学意义(P<0.05)。尿毒症肾移植患者的ABCA1与总胆固醇、他克莫司血药浓度呈正相关(P<0.05),与高密度脂蛋白胆固醇呈负相关(P<0.05),而GPIHBP1与总胆固醇、甘油三酯、他克莫司血药浓度均呈正相关(P<0.05)。血脂紊乱组患者的并发症总发生率为49.21%,明显高于血脂正常组的23.53%,差异有统计学意义(P<0.05)。结论尿毒症肾移植患者ABCA1及GPIHBP1基因水平与他克莫司血药浓度及术后血脂水平有一定相关性,检测ABCA1及GPIHBP1基因水平能够为尿毒症肾移植患者术后管理提供一定依据。 展开更多
关键词 尿毒症 肾移植 三磷酸腺苷结合盒亚家族A成员1 糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1 血脂 相关性
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自然衰老型小鼠海马及肝脏组织中胆固醇转运相关蛋白表达的研究
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作者 刘旭东 王松楠 +2 位作者 马丹 单德红 任路 《中国当代医药》 CAS 2024年第6期10-13,20,共5页
目的研究自然衰老型小鼠海马及肝脏组织胆固醇转运相关蛋白表达变化,观察衰老对胆固醇转运的影响。方法选取清洁级雄性昆明小鼠1月龄10只,10月龄10只。1月龄小鼠为对照组,10月龄小鼠为老年组,饲养7 d后,采用Y字迷宫检测小鼠行为学及记忆... 目的研究自然衰老型小鼠海马及肝脏组织胆固醇转运相关蛋白表达变化,观察衰老对胆固醇转运的影响。方法选取清洁级雄性昆明小鼠1月龄10只,10月龄10只。1月龄小鼠为对照组,10月龄小鼠为老年组,饲养7 d后,采用Y字迷宫检测小鼠行为学及记忆,采用免疫组化检测肝脏脂肪酸合酶(FASN)蛋白表达变化、海马载脂蛋白E(ApoE)蛋白表达变化,采用ELISA法检测总胆固醇、三酰甘油、高密度胆固醇及低密度胆固醇含量变化,采用Western Blot法检测肝脏三磷酸腺苷结合盒转运体A1(ABCA1)、低密度脂蛋白受体(LDLR)蛋白和海马ABCA1蛋白、ApoE蛋白表达变化。结果老年组小鼠出现摄食量减少、懒动及反应较迟钝的表现。老年组小鼠的总进臂次数和交替次数少于对照组,差异有统计学意义(P<0.05)。老年组小鼠的高密度脂蛋白胆固醇含量低于对照组,三酰甘油和低密度脂蛋白胆固醇高于对照组,差异有统计学意义(P<0.05)。老年组小鼠肝脏的FASN、LDLR和ABCA1水平低于对照组,海马组织的ApoE蛋白表达高于对照组,ABCA1蛋白表达低于对照组,差异有统计学意义(P<0.05)。结论老年组小鼠外周及中枢胆固醇代谢出现异常,可能与肝脏及海马ABCA1蛋白、ApoE蛋白、LDLR蛋白表达异常有关。 展开更多
关键词 衰老 胆固醇 三磷酸腺苷结合盒转运体A1 海马
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建立检测猕猴三磷酸腺苷结合盒转运蛋白G2的mRNA相对表达水平的RT-qPCR方法
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作者 林小瑞 张铭润 +5 位作者 王陈芸 周玮 叶尤松 龙维虎 李哲丽 唐东红 《实验动物科学》 2024年第2期35-40,共6页
目的本研究旨在建立一种实时荧光定量PCR方法,用于检测猕猴三磷酸腺苷结合盒转运蛋白G2(adenosine triphosphate-binding cassette transporter protein G2,ABCG2)mRNA的基因转录水平。方法使用NCBI上GenBank数据库猕猴(Macaca mulatta)... 目的本研究旨在建立一种实时荧光定量PCR方法,用于检测猕猴三磷酸腺苷结合盒转运蛋白G2(adenosine triphosphate-binding cassette transporter protein G2,ABCG2)mRNA的基因转录水平。方法使用NCBI上GenBank数据库猕猴(Macaca mulatta)的ABCG2核苷酸序列号NM_001032919.1及内参GAPDH核苷酸序列号NM_001195426.1,借助Primer premier 5.0软件设计PCR引物。提取猕猴新鲜肾组织的总RNA,并反转录合成cDNA。接着,利用PCR引物进行实时荧光定量PCR扩增,并根据反应体系中荧光的变化情况定量分析ABCG2的mRNA相对表达水平。结果PCR产物测序结果显示,扩增的ABCG2和GAPDH核苷酸序列与NCBI上猕猴的序列同源性分别为90.91%和91.14%。ABCG2和GAPDH的扩增效率均达到80%~120%,实时荧光定量PCR标准曲线的熔解曲线为单峰,R2接近1。结论本研究建立的检测猕猴ABCG2 mRNA实时荧光定量检测方法,为研究高尿酸血症的发病机制以及新药开发奠定基础。 展开更多
关键词 猕猴 实时荧光定量PCR 三磷酸腺苷结合盒转运蛋白G2
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ABCA3作为非小细胞肺癌的预后生物标志物及其与免疫细胞浸润的相关性
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作者 张萌萌 邵松 +1 位作者 曹冰 潘蕾 《中国医学前沿杂志(电子版)》 CSCD 北大核心 2024年第1期45-54,共10页
目的 本研究旨在基于生物信息学分析探讨ABCA3在非小细胞肺癌——肺腺癌(lung adenocarcinoma,LUAD)中的临床意义和生物学功能。方法 基于癌症基因组图谱(the Cancer Genome Atlas,TCGA),提取LUAD中ABCA3表达和相应的临床信息。使用R4.... 目的 本研究旨在基于生物信息学分析探讨ABCA3在非小细胞肺癌——肺腺癌(lung adenocarcinoma,LUAD)中的临床意义和生物学功能。方法 基于癌症基因组图谱(the Cancer Genome Atlas,TCGA),提取LUAD中ABCA3表达和相应的临床信息。使用R4.2.2软件进行统计分析。采用Wilcoxon符号秩和检验比较TCGA LUAD队列中肿瘤组织与对照组之间ABCA3的表达,以及临床病理参数与ABCA3表达水平之间的关系。根据ABCA3表达的中位数,将TCGA LUAD患者分为高表达组和低表达组。使用survival包和survminer包分析ABCA3与LUAD患者总生存(overall survival,OS)期和无进展生存(progression free survival,PFS)期的关系,并进行单因素和多因素Cox回归分析确定与LUAD预后相关的危险因素。使用rms包构建预测LUAD患者1年、2年和3年OS率的列线图模型。使用DESeq2包对高表达组和低表达组患者进行差异表达基因(differential expressed genes,DEGs)分析,并使用cluster Profil er包对DEGs进行基因本体(Gene Ontology,GO)数据库和基因组京都百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。利用CIBERSORT算法预测LUAD肿瘤样本和正常样本中22种浸润性免疫细胞的丰度,并分析ABCA3表达与免疫浸润细胞和免疫检查点之间的相关性。结果 ABCA3基因在LUAD肿瘤组织中的表达均低于配对和非配对样本正常组织(P<0.05)。ABCA3高表达LUAD患者的OS (P=0.031)和PFS (P=0.044)明显高于低表达患者。T2分期(P=0.004)和T3分期(P=0.044)患者ABCA3的表达显著低于T1分期患者。多因素Cox回归分析显示,T分期、N分期和ABCA3表达是影响LUAD预后的独立影响因素(P<0.05)。基于ABCA3表达、T分期和N分期构建的列线图预测模型的C-index为0.86,提示模型与实际结果较为一致。校准曲线中的偏差修正线接近理想曲线,提示列线图模型的预测结果与观测结果较吻合。基因集富集分析显示ABCA3高表达组主要与花生四烯酸代谢、补体和凝血级联、肠道免疫网络免疫球蛋白A产生等有关。ABCA3的表达与NRP1、TRFRSF14、TNFSF15、CD40LG、HHLA2、CD28呈明显正相关,而与IDO1、CD70、TNFSF4、CD276和VTCN1呈明显负相关(P<0.05)。12种免疫浸润细胞在高表达组和低表达组存在明显差异(P<0.05)。此外,14种免疫浸润细胞与ABCA3表达呈现明显相关性(P<0.05),包括巨噬细胞、CD4+T细胞和树突细胞。结论 ABCA3的表达与LUAD患者预后和免疫细胞浸润有关,可能是预测非小细胞肺癌预后的有价值生物标志物。 展开更多
关键词 非小细胞肺癌 肺腺癌 三磷酸腺苷结合盒转运子A3 免疫细胞浸润 预后
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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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荻草谷网蚜ABCG1基因的克隆及表达模式分析
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作者 于苗苗 张思宇 +3 位作者 宋国锋 陈巨莲 解海翠 范佳 《植物保护》 CAS CSCD 北大核心 2024年第1期256-263,285,共9页
荻草谷网蚜Sitobion miscanthi是严重威胁我国小麦生产安全的迁飞性害虫。蜕皮激素是参与蚜虫翅型分化调控的内激素,在有翅成蚜体内保持高滴度,且诱导后代产生更高比例的无翅蚜,其进出靶细胞需要经过细胞膜上特定蛋白的转运。ATP结合盒... 荻草谷网蚜Sitobion miscanthi是严重威胁我国小麦生产安全的迁飞性害虫。蜕皮激素是参与蚜虫翅型分化调控的内激素,在有翅成蚜体内保持高滴度,且诱导后代产生更高比例的无翅蚜,其进出靶细胞需要经过细胞膜上特定蛋白的转运。ATP结合盒转运蛋白家族G亚家族(ATP-binding cassette transporter G, ABCG)中的ABCG1是通过跨膜转运昆虫类固醇、对蜕皮激素信号进行负调控的功能蛋白之一,在蚜虫中尚未见报道。本文克隆了荻草谷网蚜ABCG1(SmisABCG1)基因,并进行了序列比对、系统进化分析以及不同组织部位和发育时期表达模式分析。结果显示,SmisABCG1基因的开放阅读框全长为1 851 bp,编码616个氨基酸,含7个跨膜结构域,符合ABCG蛋白家族典型结构特性,基因登录ID:OP626323。昆虫间ABCG1较保守,该蛋白系统进化关系与各自物种间亲缘关系的远近保持一致。其中,SmisABCG1与来自豌豆蚜、禾谷缢管蚜、棉蚜、花生蚜和雪松长足大蚜等的ABCG1氨基酸序列高度一致(>87%),以上蚜虫聚为一支。与SmisABCG1亲缘关系最近的是豌豆蚜的ABCG1,其次是半翅目的褐飞虱、白背飞虱和灰飞虱,与膜翅目的新疆菜叶蜂、阿里山潜蝇茧蜂以及鞘翅目的赤拟谷盗、蜂箱小甲虫亲缘关系较远。该基因在伪胚胎和成蚜阶段高表达。包含伪胚胎的有翅、无翅成蚜整蚜SmisABCG1的转录水平无显著差异,但其在来自有翅成蚜的伪胚胎中的转录水平高于无翅成蚜伪胚胎,证实无翅成蚜自身的转录水平较高,而有翅成蚜较低。进一步分析显示这一差异主要是无翅蚜胸部显著高表达所导致。基于该蛋白对蜕皮激素负调控,与有翅成蚜转录水平低,但蜕皮激素水平更高相符合。 展开更多
关键词 荻草谷网蚜 ABC转运蛋白 蜕皮激素 基因克隆 表达谱
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ABCA1 DNA启动子甲基化水平与早发急性冠脉综合征及其病变严重程度的关系
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作者 安芳 李学文 +3 位作者 杨丽荣 李覃 丛洪良 赵季红 《武警医学》 CAS 2024年第6期461-466,共6页
目的探讨三磷酸腺苷结合盒转运蛋白A1(ABCA1)DNA启动子甲基化水平与早发急性冠脉综合征(pACS)及其病变严重程度的关系。方法收集武警特色医学中心心内科2019年5-12月住院的90例早发急性冠脉综合征患者为pACS组,选取同期本院体检中心的8... 目的探讨三磷酸腺苷结合盒转运蛋白A1(ABCA1)DNA启动子甲基化水平与早发急性冠脉综合征(pACS)及其病变严重程度的关系。方法收集武警特色医学中心心内科2019年5-12月住院的90例早发急性冠脉综合征患者为pACS组,选取同期本院体检中心的88名健康体检者为对照组。使用焦磷酸测序法测定两组外周血ABCA1 DNA甲基化水平,比较两组血脂、血糖等生化指标及血清炎症标记物的浓度,并采用logistic回归分析影响pACS发病的危险因素。结果pACS组体重指数(BMI)、糖化血红蛋白(HbA1c)、低密度脂蛋白(LDL)、腰围、平均ABCA1 DNA甲基化水平以及炎症标记物白介素-1β(IL-1β)、C反应蛋白(CRP)和中性粒细胞胞外核酸网循环标志物(cfDNA/NETs)均高于对照组(P<0.05),而高密度脂蛋白(HDL-C)水平及ABCA1蛋白含量低于对照组(P<0.05)。Logistic回归分析发现,ABCA1 DNA甲基化水平(OR=7.413,95%CI:2.070~26.554)、HbA1c(OR=3.646,95%CI:1.008~13.182)、LDL(OR=15.690,95%CI:1.123~69.233)、cfDNA/NETs(OR=1.892,95%CI:1.374~2.604)及IL-1β(OR=1.177,95%CI:1.011~1.370)是pACS发生的独立危险因素,而HDL-C(OR=0.107,95%CI:0.025~0.398)是pACS的保护性因素。此外,研究表明ABCA1 DNA甲基化水平与pACS患者冠脉Gensini评分呈正相关(r=0.648,P<0.001)。结论ABCA1 DNA启动子甲基化水平是pACS发生的独立危险因素且与冠脉病变程度有关。因此,血清ABCA1-A启动子甲基化水平或许可以作为预测pACS发生风险的生物标志物而被临床应用。 展开更多
关键词 三磷酸腺苷结合盒转运蛋白A1 DNA甲基化 早发急性冠脉综合征 高密度脂蛋白胆固醇 GENSINI评分
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Drug-transporter interaction testing in drug discovery and development 被引量:1
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作者 Peter Krajcsi 《World Journal of Pharmacology》 2013年第1期35-46,共12页
The human body consists of several physiological barriers that express a number of membrane transporters. For an orally absorbed drug the intestinal, hepatic, renal and blood-brain barriers are of the greatest importa... The human body consists of several physiological barriers that express a number of membrane transporters. For an orally absorbed drug the intestinal, hepatic, renal and blood-brain barriers are of the greatest importance. The ATP-binding cassette(ABC) transporters that mediate cellular efflux and the solute carrier transporters that mostly mediate cellular uptake are the two superfamilies responsible for membrane transport of vast majority of drugs and drug metabolites. The total number of human transporters in the two superfamilies exceeds 400, and about 40-50 transporters have been characterized for drug transport. The latest Food and Drug Administration guidance focuses on P-glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide 1B1(OATP1B1), OATP1B3, organic cation transporter 2(OCT2), and organic anion transporters 1(OAT1) and OAT3. The European Medicines Agency's shortlist additionally contains the bile salt export pump, OCT1, and the multidrug and toxin extrusion transporters, multidrug and toxin ex-trusion protein 1(MATE1) and MATE2/MATE2 K. A variety of transporter assays are available to test drugtransporter interactions, transporter-mediated drugdrug interactions, and transporter-mediated toxicity. The drug binding site of ABC transporters is accessible from the cytoplasm or the inner leaflet of the plasma membrane. Therefore, vesicular transport assays utilizing inside-out vesicles are commonly used assays, where the directionality of transport results in drugs being transported into the vesicle. Monolayer assays utilizing polarized cells expressing efflux transporters are the test systems suggested by regulatory agencies. However, in some monolayers, uptake transporters must be coexpressed with efflux transporters to assure detectable transport of low passive permeability drugs. For uptake transporters mediating cellular drug uptake, utilization of stable transfectants have been suggested. In vivo animal models complete the testing battery. Some issues, such as in vivo relevance, gender difference, age and ontogeny issues can only be addressed using in vivo models. Transporter specificity is provided by using knock-out or mutant models. Alternatively, chemical knock-outs can be employed. Compensatory changes are less likely when using chemical knockouts. On the other hand, specific inhibitors for some uptake transporters are not available, limiting the options to genetic knock-outs. 展开更多
关键词 atp-binding cassette transporter Solute carrier Drug efflux Drug uptake Absorption-distribution-metabolism-excretion-toxicity Regulatory guidance ATPASE Vesicular transport Monolayer assay In vivo
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冠心病患者ABCG1、ANGPTL2启动子区甲基化与心力衰竭发生的关系研究
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作者 颜春晖 游三丽 +2 位作者 徐勤 袁李礼 王朝华 《中国循证心血管医学杂志》 2024年第2期180-184,共5页
目的分析冠状动脉粥样硬化性心脏病(冠心病)患者三磷酸腺苷结合盒转运蛋白G1(ABCG1)、血管生成素样蛋白2(ANGPTL2)启动子区甲基化与心力衰竭(心衰)发生的关系。方法选取2020年3月至2022年3月于湖南省第二人民医院收治的冠心病患者120例... 目的分析冠状动脉粥样硬化性心脏病(冠心病)患者三磷酸腺苷结合盒转运蛋白G1(ABCG1)、血管生成素样蛋白2(ANGPTL2)启动子区甲基化与心力衰竭(心衰)发生的关系。方法选取2020年3月至2022年3月于湖南省第二人民医院收治的冠心病患者120例。根据是否发生心衰,将患者分为合并心衰组(n=26)和不合并心衰组(n=94)。采用全自动生化仪检测血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)。采用心脏超声检查患者左室射血分数(LVEF)、左心室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)水平。特异性PCR检测ABCG1和ANGPTL2基因甲基化。采用实时荧光定量聚合酶链反应检测ABCG1和ANGPTL2基因mRNA表达水平。Logistic回归分析探讨影响冠心病患者发生心衰的因素。结果两组患者LDL-C、LVEF、LVEDD、LVESD、ABCG1、ANGPTL2基因启动子区甲基化等方面比较,差异具有统计学意义(P<0.05)。LVESD、LVEF、ABCG1甲基化和ANGPTL2甲基化是冠心病患者发生心衰的危险因素。ABCG1甲基化、ANGPLT2甲基化患者中LVESD水平均高于未甲基化患者(P<0.05)。ABCG1甲基化、ANGPLT2甲基化患者中LVEF水平均低于未甲基化患者(P<0.05)。合并组ABCG1、ANGPTL2基因甲基化的患者mRNA的表达量明显低于非甲基化患者(P<0.05)。结论ABCG1和ANGPTL2基因甲基化是冠心病患者发生心衰的危险因素,检测上述两基因甲基化状态可为诊治冠心病心衰提供理论支持。 展开更多
关键词 冠心病 三磷酸腺苷结合盒转运蛋白G1 血管生成素样蛋白2 心力衰竭
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P-糖蛋白抑制剂研究进展
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作者 曾怡馨 蒋建东 孔维佳 《中国药理学通报》 CAS CSCD 北大核心 2024年第12期2201-2206,共6页
P-糖蛋白(P-glycoprotein,P-gp)过表达是包括抗肿瘤药物在内多种药物治疗耐药的主要原因之一。P-gp的底物十分广泛,能够通过扭曲-挤压机制将药物排出细胞,导致耐药。为解决P-gp介导的多药耐药问题,有多种抑制剂正在被研究。该文综述了... P-糖蛋白(P-glycoprotein,P-gp)过表达是包括抗肿瘤药物在内多种药物治疗耐药的主要原因之一。P-gp的底物十分广泛,能够通过扭曲-挤压机制将药物排出细胞,导致耐药。为解决P-gp介导的多药耐药问题,有多种抑制剂正在被研究。该文综述了目前能够抑制P-gp的小分子化合物、天然来源化合物和药物辅料,并总结了目前P-gp抑制剂的作用机制,主要有竞争性或非竞争性抑制、刺激ATP酶活性、下调表达量和变构调节。目前主要是药物相互作用和毒性反应限制了其临床应用。 展开更多
关键词 P-糖蛋白 ATP结合盒转运体 多药耐药 药物相互作用 天然产物 辅料
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葛花提取物通过激活PPARγ上调ABCA1的表达而抑制THP-1源性泡沫细胞形成
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作者 朱容蓉 陈梦娇 +4 位作者 赵真旺 刘嘉怡 吴剑锋 王宇菲 张敏 《中国动脉硬化杂志》 CAS 2024年第5期395-401,共7页
[目的]探寻葛花提取物(PFE)对巨噬细胞源性泡沫细胞脂质蓄积的影响。[方法]通过MTT法筛选PFE对THP-1源性泡沫细胞的作用浓度,采用油红O染色和胆固醇检测试剂盒检测细胞内脂质蓄积情况,采用胆固醇流出试剂盒检测细胞的胆固醇流出水平,使... [目的]探寻葛花提取物(PFE)对巨噬细胞源性泡沫细胞脂质蓄积的影响。[方法]通过MTT法筛选PFE对THP-1源性泡沫细胞的作用浓度,采用油红O染色和胆固醇检测试剂盒检测细胞内脂质蓄积情况,采用胆固醇流出试剂盒检测细胞的胆固醇流出水平,使用RT-qPCR和Western blot检测mRNA和蛋白表达。[结果]PFE显著降低THP-1源性泡沫细胞内的脂质蓄积。PFE不影响CD36、清道夫受体AⅠ(SR-AⅠ)、固醇调节元件结合蛋白2(SREBP2)及3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)的mRNA表达,但能上调ATP结合盒转运体A1(ABCA1)的mRNA和蛋白表达水平(P<0.05),促进巨噬细胞源性泡沫细胞胆固醇流出(P<0.01)。PFE可以激活过氧化物酶体增殖物激活受体γ(PPARγ)的活性(P<0.01)及上调其mRNA和蛋白表达水平(P<0.05)。与PFE对照组相比,加入GW9662处理后PPARγ和ABCA1的蛋白表达水平均下降(P<0.01),胆固醇流出水平降低(P<0.01)。[结论]PFE可显著改善THP-1源性泡沫细胞内的脂质蓄积,通过PPARγ上调ABCA1表达及其介导的胆固醇流出抑制泡沫细胞形成。 展开更多
关键词 葛花提取物 泡沫细胞 ATP结合盒转运体A1 过氧化物酶体增殖物激活受体Γ
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