NF-κB的研究进展

核因子κB(NF-κB)是一种广泛存在于真核细胞内的基因多向性转录因子,属于Rel家族,于1986年首次在小鼠B淋巴细胞的核抽提物中发现,因能与免疫球蛋白κ链基因的     

Novel IκB kinase inhibitors for treatment of nuclear factor-κB-related diseases

Introduction: NF-κB is a key regulator of inflammation and immunity in cancer development. The IκB kinase (IKK) is a multisubunit complex containing catalytic subunits termed IKK-α, -β and -γ. It is well known that many pro-inflammatory stimuli require the IKK-β subunit for NF-κB activation.

Areas covered: NF-κB affects the progression of inflammation-related diseases, such as myocardial ischemia, bronchial asthma, arthritis, cancer and other diseases. We review the characteristics and effects of these inhibitors on inflammatory and other diseases.

Expert opinion: Various synthesized IKK inhibitors have been developed and they will be used clinically in the near future.     

κ阿片受体分子模拟及其与非肽类κ阿片激动剂的作用

目的：研究了κ阿片受体及其与非肽类激动剂的作用机制。方法;以细菌视紫红质为模板,模建κ阿片受体七个跨膜区的三维结构,将五个高活性非肽类激动剂对接以螺旋区内,研究作用机制。结果：（１）四氢吡咯环氮原子与Ａｓｐ１３８羧基成氢键;（２）乙酰胺羰基氧与受体Ｓｅｒ１８７间存在在氢键作用;（３）与乙酰胺相连的疏水基团处于由Ｖａｌ２３９,Ｖａｌ１２３６,Ｐｈｅ２３５,Ｖａｌ２３２,Ｌｅｕ１８６和Ｔｒｐ１８３构成     

Sandwich ELISA法测定NF-κB

目的　建立一种操作简便、安全的核因子 κB(NF κB)活性检测方法。方法　采用夹心酶联免疫吸附测试法(SandwichELISA) ,酶标仪 ,验证NF κB活化的抑制剂反义白介素 1受体相关激酶 2 (IRAK 2 )寡核苷酸和N α Tosyl L lysinechloromethylketone(TLCK)对NF κB活性的抑制作用。结果　SandwichELISA测定结果表明 ,与对照组相比 ,用不同浓度反义IRAK 2寡核苷酸 (1,2 ,3,4μg )或TLCK(1,10 ,10 0 μmol·L-1)处理细胞后 ,NF κB活化受到不同程度的抑制 ,表现为吸光度值下降的幅度不同。结论　Sand wichELISA法可用于NF κB活性检测。     

Inhibition of Nuclear Transcription Factor-κB by Specific IκB Kinase Peptide Inhibitor

Pharmaceutical Research -     

新止痒镇痛阿片κ激动剂

nalfurafinehydrochloride(TRK 82 0 )在体外用电刺激的豚鼠回肠纵肌和小鼠输精管测定了nalfurafinehydrochloride(TRK 82 0 )的受体选择性和激动剂活性 (纳洛酮用于 μ受体 ,纳屈吲哚用于δ受体 ,norbinaltorphimine用于κ受体测试 )。TRK 82 0对以上两种组织的效应均比吗啡强 4 0 0 0倍 ,(豚鼠回肠IC50 =0 .0 0 4 8nmol·L- 1,小鼠输精管IC50 =0 .0 36nmol·L- 1) ,对κ受体有高选择性 (豚鼠回肠 μ/κ =2 79,小鼠输精管δ/κ =135 )。在表达大鼠野生型 μ ,δ和κ阿片受体的CHO细胞膜标本上进一步测定了TRK - 82 0的激动剂活性…     

NF—κB的研究进展

核因子κＢ（ＮＦ－κＢ）是能调节多种炎症和免疫基因表达的一种重要的转录调节因子,它在胞浆内与ＮＦ－κＢ抑制蛋白（ＩκＢ）结合呈非活性状态,一旦被病毒、氧化剂、炎症细胞因子等刺激剂激活后便与ＩκＢ解离而转入核内与特异的启动子结合,从而调控基因的表达。ＮＦ－κＢ过度激活与许多病理现象有关,例如类风湿性关节炎、哮喘、艾滋病、动脉粥样硬化、神经退行性疾病等,而ＮＦ－κＢ被抑制则与癌症、免疫细胞发育不全、细     

宝华玉兰种子提取物对NF-κB及IκBα表达的抑制作用

目的探讨宝华玉兰种子提取物对核转录因子-κB(NF-κB)、核转录因子-κB抑制蛋白α(IκBα)表达的抑制作用机制。方法使用宝华玉兰种子提取物处理人肝癌细胞HepG2后,用Western blotting法检测NF-κB及IκBα蛋白的表达变化情况。结果宝华玉兰种子提取物对IκBα的磷酸化及降解有抑制作用。宝华玉兰种子提取物可有效抑制NF-κB介导的基因转录。结论宝华玉兰种子提取物可能通过抑制IκBα磷酸化及降解,阻断NF-κB活性,进而抑制COX-2而发挥其抗炎和抗肿瘤作用。     

Theophylline inhibits NF-κB activation and IκBα degradation in human pulmonary epithelial cells

Previous studies demonstrated that theophylline modulates NF-kappaB activation in mast cells and pulmonary epithelial cells. We examined whether or not this modulation of NF-kappaB activation by theophylline is due to inhibition of the degradation of the IKBalpha protein, which suppresses NF-kappaB activation. TNF-alpha-induced NF-kappaB activation in a human pulmonary epithelial cell line (A549) was evaluated by Western blotting and a chloramphenicol acetyltransferase (CAT) assay. Expression of the IkappaBalpha protein was evaluated by Western blotting. Western blotting of nuclear extracts of A549 cells demonstrated that theophylline suppresses NF-kappaB-p65 nuclear translocation. The CAT assay indicated that NF-kappaB-dependent reporter gene expression is inhibited in A549 cells pretreated with theophylline. Western blotting of cytoplasmic extracts of A549 cells revealed that this inhibition was linked to theophylline-induced protection of expression of the IkappaBalpha protein. Moreover, theophylline inhibited interleukin-6 production induced by TNF-alpha in A549 cells. These findings are consistent with the idea that theophylline suppresses the production of proinflammatory cytokines via inhibition of NF-kappaB activation through protection of the IkappaBalpha protein.     

NF-κB国外最新研究进展

NF-κappaB(NF-κB)在致炎性转录因子表达时无所不在,调节涉及细胞转化、存活、增殖、侵袭、血管发生、转移和炎症在内的500多个基因的表达,同时,NF-κB信号转导途径参与了炎症、细胞凋亡、免疫反应等病理过程,所以其信号通路在药物介入方面成为潜在靶向目标。本文就国外学者关于NF-κB的最新论著和研究做一综述如下。     

同型半胱氨酸对人脐静脉内皮细胞IκB和NF-κB表达的影响

目的:观察同型半胱氨酸(Hcy)对人脐静脉内皮细胞(HUVECs)核因子(NF)-κB的表达、激活的影响及其诱导动脉粥样硬化形成的分子机制。方法:将体外培养的HUVECs分为对照组、2.5(H1)、5(H2)、10(H3)及15mmol/L(H4)5组,培养24h。通过四甲基噻唑氮蓝(MTT)比色法测定细胞活力,采用RT-PCR法检测NF-κBp65mRNA的表达,Westernblot检测NF-κB抑制蛋白-α(IκB-α)的蛋白降解,免疫组化法检测NF-κB的核转移趋势。结果:H2、H3、H4组HUVECs细胞活力较对照组明显下降(P<0.01);Hcy可使NF-κBp65mRNA的表达明显增强(P<0.05或P<0.01);Hcy可促进IκB-α蛋白降解,且呈现明显的剂量依赖性;Hcy处理HUVECs后,大量的NF-κBp65从细胞质进入细胞核。结论:Hcy可通过增强NF-κBp65mRNA的表达,加速IκB-α蛋白的降解,促进NF-κBp65的释放、活化,从而转移进细胞核,调节其下游的趋化因子、细胞黏附分子的表达,促进动脉粥样硬化的形成和发展。     

NF-κB国外最新研究进展

NF-icappaB(NF-κB)在致炎性转录因子表达时无所不在,调节涉及细胞转化、存活、增殖、侵袭、血管发生、转移和炎症在内的500多个基因的表达,同时,NF-κB信号转导途径参与了炎症、细胞凋亡、免疫反应等病理过程,所以其信号通路在药物介入方面成为潜在靶向目标.     

NF-κB在胃癌中的作用

核因子-κB(NF-κB)作为一种特异性转录因子结合在编码免疫球蛋白kappa轻链基因的启动子上,其作用与发育、损伤、炎症和肿瘤的发病机制有关。越来越多的证据表明,NF-κB与癌症密切相关,在癌症的发生、发展过程中发挥着关键作用[1-2]。     

Targeting NF-κB for colorectal cancer

Importance of the field: Colorectal cancer (CRC) is the second leading cause of cancer death. Progress has been made in the development of chemotherapy for advanced CRC. Targeted therapies against VEGF or EGFR are now commonly used. Many cases show that tolerance develops to such treatments and thus new strategies are required to replace or complement current therapies. The NF-κB signaling pathway plays critical roles in physiological and pathological processes, and the relationship between colon cancer development and NF-κB is becoming clear.

Areas covered in this review: We discuss evidence for the participation of activated NF-κB in carcinogenesis and consider the possibility of NF-κB being a target for CRC treatment.

What the reader will gain: NF-κB activation might be involved in development of not only colitis-associated cancer, but also sporadic CRC. NF-κB activation is associated with hallmarks of cancer. Constitutive NF-κB activation is frequently observed in CRC and is associated with angiogenesis and resistance to chemotherapy. Several NF-κB inhibitors have proven to be useful.

Take home message: Induction of NF-κB activation leads to resistance to chemotherapy and constitutively activated NF-κB can often be seen in CRC. Anti-NF-κB therapy may rescue many cases of CRC and should be examined further for use as a therapy target.     

κ阿片受体介导的降血压作用

目的观察κ阿片受体激动剂U50488H对大鼠血压的影响并探讨其作用机制。方法监测正常大鼠心率(HR)、动脉压(ABP)、左心室内压(LVP)及左室的收缩(+dp/dtm ax)和舒张功能(-dp/dtm ax)等血流动力学指标和尿量的变化;分离正常大鼠腹主动脉,测定血管张力的变化。结果在整体水平,静脉注射U50488H可降低大鼠HR、ABP、LVP及±dp/dtm ax;而且可增加大鼠的尿量。在离体水平,U50488H对大鼠腹主动脉具有明显的剂量依赖性舒张作用;以上效应均可被选择性κ阿片受体阻断剂nor-BNI所阻断。结论激动κ阿片受体可引起降压作用,抑制心肌收缩力、舒张血管和利尿是其降压的主要机制。