Neuromedin B(NMB)is a member of mammalian bombesin-like peptide family and almost all its potent biological actions take place exclusively through its receptor NMBR,which has been identified as a G-protein couple rece...Neuromedin B(NMB)is a member of mammalian bombesin-like peptide family and almost all its potent biological actions take place exclusively through its receptor NMBR,which has been identified as a G-protein couple receptor with seven trans-membrane regions.NMB and NMBR represent an interesting signaling axis over which NMB/NMBR perform multiple biological activities,in particularly,they have been highlighted in the regulation of the immunology system.This review aims to provide a brief overview of the recent advancements in our understanding regarding the potential immunological functions of NMB and NMBR in cell proliferation,tumorigenesis,angiogenesis,neurogenic inflammation,anti-influenza A virus(IAV)infections,and briefly discusses the potential importance of these observations.All these implicated that targeting NMBR or developing analogues of NMB may represent a useful strategy for development of new anti-IAV agents.展开更多
目的:探讨神经调节素B受体(neuromedin B receptor,NMBR)在妊娠小鼠子宫平滑肌细胞中mRNA、蛋白时空表达的变化及其与分娩启动的关系和机制。方法:按妊娠阶段的不同,将小鼠分为未孕组、早孕组、中孕组、晚孕组、产时组和产后组,每组12...目的:探讨神经调节素B受体(neuromedin B receptor,NMBR)在妊娠小鼠子宫平滑肌细胞中mRNA、蛋白时空表达的变化及其与分娩启动的关系和机制。方法:按妊娠阶段的不同,将小鼠分为未孕组、早孕组、中孕组、晚孕组、产时组和产后组,每组12例。应用半定量RT-PCR和Western免疫印迹技术分别检测子宫平滑肌中NMBR,IL-6和HSP70mRNA及蛋白表达;利用NoShift转录因子分析法检测NF-κB-P65的DNA结合活性,并分析各指标与分娩的关系及其相关性。结果:产时组NMBRmRNA的相对表达量显著高于未孕、早孕、晚孕、产后组(P<0.05),但与中孕组相比差异无统计学意义(P>0.05);产时组NMBR蛋白表达量显著高于其它各组(P<0.01)。NF-κB-P65DNA结合活性产时组显著高于未孕、晚孕和产后组(P<0.05)。IL-6mRNA表达产时组显著高于未孕、晚孕和产后组(P<0.05),其蛋白表达产时组亦显著高于未孕和产后组(P<0.05)。HSP70mRNA表达量产时组显著高于未孕和产后组(P<0.05),HSP70蛋白的表达量产时组明显高于晚孕、未孕组(P<0.05)。临产前后子宫平滑肌细胞P65DNA结合活性、IL-6mRNA的表达均与NMBRmRNA的变化呈正相关(r=0.40,P<0.01;r=0.30,P<0.05);P65,HSP70mRNA的变化亦与NMBR的变化呈正相关(r=0.40,P<0.01;r=0.49,P<0.01);但HSP70与P65无相关性。结论:子宫平滑肌细胞中NMBRmRNA和蛋白表达在临产时达最高峰。NMBR可借助NF-κB P65-IL-6通路、通过调节HSP70表达参与分娩发动和维持,但其对HSP70表达的影响不依赖P65途径。展开更多
神经介素B(neuromedin B,NMB)及受体(NMB receptor,NMBR)通过NF-κB信号通路参与抑制甲型流感病毒(influenza A virus,IAV)H1N1亚型(IAV/H1N1)的感染。但关于NMB和NMBR对NF-κB信号通路相关泛素蛋白酶的调控如何,尚未见报道。为探究NMB...神经介素B(neuromedin B,NMB)及受体(NMB receptor,NMBR)通过NF-κB信号通路参与抑制甲型流感病毒(influenza A virus,IAV)H1N1亚型(IAV/H1N1)的感染。但关于NMB和NMBR对NF-κB信号通路相关泛素蛋白酶的调控如何,尚未见报道。为探究NMB和NMBR调控IAV诱导的NF-κB信号通路相关的泛素蛋白酶表达的影响,本研究基于IAV/H9N2感染sh-NMBR细胞与NMB刺激的A549细胞,采用RT-PCR、qRT-PCR及Western blot(WB)分析NMB和NMBR对H9N2感染引起的NF-κB信号通路相关的E3泛素连接酶Mind bomb-2(MIB2)和Ring Finger Protein 8(RNF8)及去泛素蛋白酶Cylindromatosis(CYLD)的表达变化。结果显示:H9N2感染sh-NMBR细胞中,RNF8和CYLD表达增加,MIB2表达和P65磷酸化水平降低;NMB激活A549细胞中NMBR的表达后,诱导细胞中RNF8和CYLD的表达水平下降,MIB2表达和P65磷酸化水平增加。结果表明:NMB和NMBR通过调控IAV/H9N2感染诱导的泛素蛋白酶的表达和P65活性,从而影响IAV/H9N2感染激活的NF-κB信号通路的功能,该结果为深入研究NMB和NMBR抑制甲型流感病毒感染的作用机制提供了理论基础。展开更多
TPP-Ⅰ(tripeptidyl peptidase-Ⅰ) protein turnover was studied by observing the role of rat TPP-Ⅰ in neuromedin B(NMB) and other neuropeptides degradations in some physiological situations. The mixtures of rat TPP-Ⅰ ...TPP-Ⅰ(tripeptidyl peptidase-Ⅰ) protein turnover was studied by observing the role of rat TPP-Ⅰ in neuromedin B(NMB) and other neuropeptides degradations in some physiological situations. The mixtures of rat TPP-Ⅰ with each of NMB, other neuropeptides and Ala-Ala-Phe-MCA were made respectively under the same conditions. The reaction was observed at different timeand monitored by means of high performance liquid chromatography(HPLC) and time-of-flight mass spectrometry(TOF-MS) in vitro. NMB was broken down at the same degree as Ala-Ala-Phe-MCA by rat TPP-Ⅰ and Gly-Asn-Leu was released within 16 h, but other neuropeptides were not digested within 24 h. TPP-Ⅰ is the predominant proteolytic enzyme responsible for the intracellular degradation of neuromedin B. NMB has recently been found to be a good natural substrate for rat lysosomal TPP-Ⅰ.展开更多
基金National Science Foundation of China(U1805231)National Program for Innovation and Entrepreneurship Training of University Students(202110389008)+2 种基金Special Fund Project for Scientific and Technological Innovation of Fujian Agriculture and Forestry University(CXZX2018015,CXZX2020060A)Key Laboratory Project of Animal Infectious Disease Control and Biotechnology in Fujian Province(2018KF03)National Science Foundation of Fujian Province(2020J01539).
文摘Neuromedin B(NMB)is a member of mammalian bombesin-like peptide family and almost all its potent biological actions take place exclusively through its receptor NMBR,which has been identified as a G-protein couple receptor with seven trans-membrane regions.NMB and NMBR represent an interesting signaling axis over which NMB/NMBR perform multiple biological activities,in particularly,they have been highlighted in the regulation of the immunology system.This review aims to provide a brief overview of the recent advancements in our understanding regarding the potential immunological functions of NMB and NMBR in cell proliferation,tumorigenesis,angiogenesis,neurogenic inflammation,anti-influenza A virus(IAV)infections,and briefly discusses the potential importance of these observations.All these implicated that targeting NMBR or developing analogues of NMB may represent a useful strategy for development of new anti-IAV agents.
文摘目的:探讨神经调节素B受体(neuromedin B receptor,NMBR)在妊娠小鼠子宫平滑肌细胞中mRNA、蛋白时空表达的变化及其与分娩启动的关系和机制。方法:按妊娠阶段的不同,将小鼠分为未孕组、早孕组、中孕组、晚孕组、产时组和产后组,每组12例。应用半定量RT-PCR和Western免疫印迹技术分别检测子宫平滑肌中NMBR,IL-6和HSP70mRNA及蛋白表达;利用NoShift转录因子分析法检测NF-κB-P65的DNA结合活性,并分析各指标与分娩的关系及其相关性。结果:产时组NMBRmRNA的相对表达量显著高于未孕、早孕、晚孕、产后组(P<0.05),但与中孕组相比差异无统计学意义(P>0.05);产时组NMBR蛋白表达量显著高于其它各组(P<0.01)。NF-κB-P65DNA结合活性产时组显著高于未孕、晚孕和产后组(P<0.05)。IL-6mRNA表达产时组显著高于未孕、晚孕和产后组(P<0.05),其蛋白表达产时组亦显著高于未孕和产后组(P<0.05)。HSP70mRNA表达量产时组显著高于未孕和产后组(P<0.05),HSP70蛋白的表达量产时组明显高于晚孕、未孕组(P<0.05)。临产前后子宫平滑肌细胞P65DNA结合活性、IL-6mRNA的表达均与NMBRmRNA的变化呈正相关(r=0.40,P<0.01;r=0.30,P<0.05);P65,HSP70mRNA的变化亦与NMBR的变化呈正相关(r=0.40,P<0.01;r=0.49,P<0.01);但HSP70与P65无相关性。结论:子宫平滑肌细胞中NMBRmRNA和蛋白表达在临产时达最高峰。NMBR可借助NF-κB P65-IL-6通路、通过调节HSP70表达参与分娩发动和维持,但其对HSP70表达的影响不依赖P65途径。
文摘神经介素B(neuromedin B,NMB)及受体(NMB receptor,NMBR)通过NF-κB信号通路参与抑制甲型流感病毒(influenza A virus,IAV)H1N1亚型(IAV/H1N1)的感染。但关于NMB和NMBR对NF-κB信号通路相关泛素蛋白酶的调控如何,尚未见报道。为探究NMB和NMBR调控IAV诱导的NF-κB信号通路相关的泛素蛋白酶表达的影响,本研究基于IAV/H9N2感染sh-NMBR细胞与NMB刺激的A549细胞,采用RT-PCR、qRT-PCR及Western blot(WB)分析NMB和NMBR对H9N2感染引起的NF-κB信号通路相关的E3泛素连接酶Mind bomb-2(MIB2)和Ring Finger Protein 8(RNF8)及去泛素蛋白酶Cylindromatosis(CYLD)的表达变化。结果显示:H9N2感染sh-NMBR细胞中,RNF8和CYLD表达增加,MIB2表达和P65磷酸化水平降低;NMB激活A549细胞中NMBR的表达后,诱导细胞中RNF8和CYLD的表达水平下降,MIB2表达和P65磷酸化水平增加。结果表明:NMB和NMBR通过调控IAV/H9N2感染诱导的泛素蛋白酶的表达和P65活性,从而影响IAV/H9N2感染激活的NF-κB信号通路的功能,该结果为深入研究NMB和NMBR抑制甲型流感病毒感染的作用机制提供了理论基础。
文摘TPP-Ⅰ(tripeptidyl peptidase-Ⅰ) protein turnover was studied by observing the role of rat TPP-Ⅰ in neuromedin B(NMB) and other neuropeptides degradations in some physiological situations. The mixtures of rat TPP-Ⅰ with each of NMB, other neuropeptides and Ala-Ala-Phe-MCA were made respectively under the same conditions. The reaction was observed at different timeand monitored by means of high performance liquid chromatography(HPLC) and time-of-flight mass spectrometry(TOF-MS) in vitro. NMB was broken down at the same degree as Ala-Ala-Phe-MCA by rat TPP-Ⅰ and Gly-Asn-Leu was released within 16 h, but other neuropeptides were not digested within 24 h. TPP-Ⅰ is the predominant proteolytic enzyme responsible for the intracellular degradation of neuromedin B. NMB has recently been found to be a good natural substrate for rat lysosomal TPP-Ⅰ.
