肝X受体(liver X receptor,LXR)是细胞核受体超家族的成员之一,也曾被称为孤儿受体。现已经明确LXR包括LXRα(NR1H3)和LXRβ(NR1H2)两种同源亚型。研究发现,LXR与甾醇调节元件结合蛋白(SREBP-1)、氧化修饰低密度脂蛋白(oxLDL)、一氧化氮...肝X受体(liver X receptor,LXR)是细胞核受体超家族的成员之一,也曾被称为孤儿受体。现已经明确LXR包括LXRα(NR1H3)和LXRβ(NR1H2)两种同源亚型。研究发现,LXR与甾醇调节元件结合蛋白(SREBP-1)、氧化修饰低密度脂蛋白(oxLDL)、一氧化氮(NO)、基质金属蛋白酶(MMPs)、Endoglin(CD105)、人绒毛膜促性腺激素(hCG)等存在联系,而这些因素又参与子痫前期的发病,证实了LXR与脂类的代谢、血管内皮的损伤、滋养细胞的增殖和侵袭等有关。因此LXR表达异常可能在子痫前期的发生发展中起重要作用。展开更多
Osteoclast differentiation depends on receptor activator of nuclear factor-κB(RANK) signaling,which can be divided into triggering,amplifying and targeting phases based on how active the master regulator nuclear fact...Osteoclast differentiation depends on receptor activator of nuclear factor-κB(RANK) signaling,which can be divided into triggering,amplifying and targeting phases based on how active the master regulator nuclear factor of activated T-cells cytoplasmic 1(NFATc1) is. The triggering phase is characterized by immediateearly RANK signaling induced by RANK ligand(RANKL) stimulation mediated by three adaptor proteins,tumor necrosis factor receptor-associated factor 6,Grb-2-associated binder-2 and phospholipase C(PLC)γ2,leading to activation of IκB kinase,mitogen-activated protein kinases and the transcription factors nuclear factor(NF)-κB and activator protein-1(AP-1). Mice lacking NF-κB p50/p52 or the AP-1 subunit c-Fos(encoded by Fos) exhibit severe osteopetrosis due to a differentiation block in the osteoclast lineage. The amplification phase occurs about 24 h later in a RANKLinduced osteoclastogenic culture when Ca2+ oscillation starts and the transcription factor NFATc1 is abundantly produced. In addition to Ca2+ oscillation-dependent nuclear translocation and transcriptional auto-induction of NFATc1,a Ca2+ oscillation-independent,osteoblastdependent mechanism stabilizes NFATc1 protein in dif-ferentiating osteoclasts. Osteoclast precursors lacking PLCγ2,inositol-1,4,5-trisphosphate receptors,regulator of G-protein signaling 10,or NFATc1 show an impaired transition from the triggering to amplifying phases. The final targeting phase is mediated by activation of numerous NFATc1 target genes responsible for cell-cell fusion and regulation of bone-resorptive function. This review focuses on molecular mechanisms for each of the three phases of RANK signaling during osteoclast differentiation.展开更多
AIM: To investigate the role of TR3 in induction of apoptosis in gastric cancer cells. METHODS: Human gastric cancer cell line, MGC80-3, was used. Expression of TR3 mRNA and its protein was detected by Northern blot a...AIM: To investigate the role of TR3 in induction of apoptosis in gastric cancer cells. METHODS: Human gastric cancer cell line, MGC80-3, was used. Expression of TR3 mRNA and its protein was detected by Northern blot and Western blot. Localization of TR3 protein was showed by immunofluorescence analysis under laser-scanning confocal microscope. Apoptotic morphology was observed by DAPI fluorescence staining, and apoptotic index was counted among 1000 cells randomly. Stable transfection assay was carried out by Lipofectamine. RESULTS: Treatment of MGC80-3 cells with TPA and VP-16 resulted in apoptosis, accompanied by the repression of Bcl-2 protein in a time-dependent manner. At the same time, TPA and VP-16 also up-regulated expression level of TR3 mRNA in MGC80-3 cells that expressed TR3 mRNA. When antisense-TR3 expression vector was transfected into the cells, expression of TR3 protein was repressed. In this case, TPA and VP-16 did not induce apoptosis. In addition, TPA and VP-16-induced apoptosis involved in translocation of TR3. In MGC80-3 cells, TR3 localized concentrative in nucleus, after treatment of cells with TPA and VP-16, TR3 translocated from nucleus to cytosol obviously. However, when this nuclear translocation was blocked by LMB, apoptosis was not occurred in MGC80-3 cells even in the presence of TPA and VP-16. CONCLUSION: Induction of apoptosis by TPA and VP-16 is through induction of TR3 expression and translocation of TR3 from nucleus to cytosol, which may be a novel signal pathway for TR3, and represent the new biological function of TR3 to exert its effect on apoptosis in gastric cancer cells.展开更多
目的探讨人前列腺癌细胞系DU145细胞中肝X受体(liver X receptor,LXR)特异性激动剂GW3965对核受体结合蛋白1(nuclear receptor binding protein 1,NRBP1)的表达调控作用。方法采用MTT法检测不同浓度GW3965(浓度分别为0.5、5、10μmol/L...目的探讨人前列腺癌细胞系DU145细胞中肝X受体(liver X receptor,LXR)特异性激动剂GW3965对核受体结合蛋白1(nuclear receptor binding protein 1,NRBP1)的表达调控作用。方法采用MTT法检测不同浓度GW3965(浓度分别为0.5、5、10μmol/L)作用24 h后对DU145细胞增殖的影响。在人前列腺癌DU145细胞中用LXR的特异性激动剂GW3965处理24 h后,经逆转录-聚合酶链反应(RT-PCR)检测LXR特异性靶基因三磷腺苷结合A1(ATP-bindingcassette A1,ABCA1)转录水平的表达情况;随后在转录水平和翻译水平检测NRBP1的表达。结果 LXR特异性激动剂GW3965各实验组对细胞的活性和增殖无影响(P>0.05)。GW3965作用于DU145细胞后,ABCA1转录水平呈剂量依赖性升高,表明LXR在DU145细胞中具有功能活性。LXR经过活化后在转录和翻译水平对NRBP1的抑制作用呈剂量依赖性降低。结论 LXR在DU145细胞中可抑制NRBP1的表达。展开更多
文摘肝X受体(liver X receptor,LXR)是细胞核受体超家族的成员之一,也曾被称为孤儿受体。现已经明确LXR包括LXRα(NR1H3)和LXRβ(NR1H2)两种同源亚型。研究发现,LXR与甾醇调节元件结合蛋白(SREBP-1)、氧化修饰低密度脂蛋白(oxLDL)、一氧化氮(NO)、基质金属蛋白酶(MMPs)、Endoglin(CD105)、人绒毛膜促性腺激素(hCG)等存在联系,而这些因素又参与子痫前期的发病,证实了LXR与脂类的代谢、血管内皮的损伤、滋养细胞的增殖和侵袭等有关。因此LXR表达异常可能在子痫前期的发生发展中起重要作用。
基金Supported by Grants from MEXT Japan,No.23790265(to Kuroda Y)and No.21390425(to Matsuo K)
文摘Osteoclast differentiation depends on receptor activator of nuclear factor-κB(RANK) signaling,which can be divided into triggering,amplifying and targeting phases based on how active the master regulator nuclear factor of activated T-cells cytoplasmic 1(NFATc1) is. The triggering phase is characterized by immediateearly RANK signaling induced by RANK ligand(RANKL) stimulation mediated by three adaptor proteins,tumor necrosis factor receptor-associated factor 6,Grb-2-associated binder-2 and phospholipase C(PLC)γ2,leading to activation of IκB kinase,mitogen-activated protein kinases and the transcription factors nuclear factor(NF)-κB and activator protein-1(AP-1). Mice lacking NF-κB p50/p52 or the AP-1 subunit c-Fos(encoded by Fos) exhibit severe osteopetrosis due to a differentiation block in the osteoclast lineage. The amplification phase occurs about 24 h later in a RANKLinduced osteoclastogenic culture when Ca2+ oscillation starts and the transcription factor NFATc1 is abundantly produced. In addition to Ca2+ oscillation-dependent nuclear translocation and transcriptional auto-induction of NFATc1,a Ca2+ oscillation-independent,osteoblastdependent mechanism stabilizes NFATc1 protein in dif-ferentiating osteoclasts. Osteoclast precursors lacking PLCγ2,inositol-1,4,5-trisphosphate receptors,regulator of G-protein signaling 10,or NFATc1 show an impaired transition from the triggering to amplifying phases. The final targeting phase is mediated by activation of numerous NFATc1 target genes responsible for cell-cell fusion and regulation of bone-resorptive function. This review focuses on molecular mechanisms for each of the three phases of RANK signaling during osteoclast differentiation.
基金the National Outstanding Youth Science foundation of China (B type,39825502)the National Natural Science Foundation of China (39880015,30170477)the Natural Science Foundation of Fujian Province (C0110004).
文摘AIM: To investigate the role of TR3 in induction of apoptosis in gastric cancer cells. METHODS: Human gastric cancer cell line, MGC80-3, was used. Expression of TR3 mRNA and its protein was detected by Northern blot and Western blot. Localization of TR3 protein was showed by immunofluorescence analysis under laser-scanning confocal microscope. Apoptotic morphology was observed by DAPI fluorescence staining, and apoptotic index was counted among 1000 cells randomly. Stable transfection assay was carried out by Lipofectamine. RESULTS: Treatment of MGC80-3 cells with TPA and VP-16 resulted in apoptosis, accompanied by the repression of Bcl-2 protein in a time-dependent manner. At the same time, TPA and VP-16 also up-regulated expression level of TR3 mRNA in MGC80-3 cells that expressed TR3 mRNA. When antisense-TR3 expression vector was transfected into the cells, expression of TR3 protein was repressed. In this case, TPA and VP-16 did not induce apoptosis. In addition, TPA and VP-16-induced apoptosis involved in translocation of TR3. In MGC80-3 cells, TR3 localized concentrative in nucleus, after treatment of cells with TPA and VP-16, TR3 translocated from nucleus to cytosol obviously. However, when this nuclear translocation was blocked by LMB, apoptosis was not occurred in MGC80-3 cells even in the presence of TPA and VP-16. CONCLUSION: Induction of apoptosis by TPA and VP-16 is through induction of TR3 expression and translocation of TR3 from nucleus to cytosol, which may be a novel signal pathway for TR3, and represent the new biological function of TR3 to exert its effect on apoptosis in gastric cancer cells.
