Endothelin-1 and a number of other genes expressd primarily in endothelial cells(EC)require a functional GATA element in their promoter region.The widely expressed zinc finger DNA binding protein GATA-2 has been chara...Endothelin-1 and a number of other genes expressd primarily in endothelial cells(EC)require a functional GATA element in their promoter region.The widely expressed zinc finger DNA binding protein GATA-2 has been characterized as the likely GATA factor which binds these GATA elements.To understand the specificity of this interaction,and to investigate the potential for regulation of GATA-2 activity,we have studied translation and post-translational modification of the GATA-2 protein. A specific antiserum immunoprecipitated a 52kDa GATA-2 protein from [35-S] methionine-labeled EC,as well as a wide variety of cultured human cell lines which express GATA-2 mRNA. Immunoprecipitation experiments with [32-P]-orthophosphate labeled cells indicated that GATA-2 is similarly phosphorylated in EC and non-EC lines. Thus the apparent cell-specific activity of this transcription factor is not regulated by translation or phosphorylation, and must derive from the interaction of GATA-2 with other nuclear proteins in the EC.Further studies investigated the potential regulation of GATA-2 phosphorylation in EC. Phosphoamino acid analysis indicated that GATA-2 is phosphorylated on serine and threonine residues in EC.The hasal phosphorylation of GATA-2 was rapidly and markedly increased when EC were treated with calcium ionophore A23187, while phorbol ester and forskolin had no effect.Phosphopeptide map analysis showed that A23187 induced phosphorylation of at least two additional sites in GATA-2.Gel shift assays employing nuclear extracts isolated from EC that had been treated with A23187 had a different DNA binding pattern when compared to control.This regulated phosphorylation of GATA-2 may provide a signaling pathway for hormonal regulation of endothelial cell genes such as endothelin-1 which alter their rate of transcription in response to increased intracellular calcium.展开更多
The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane pr...The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane proteins aremembers of the basic helix-loop-helix-leucine zipper (bHLHZip) family of transcription factors. They activate the expression of at least 30 genes involved in the synthesis of cholesterol and lipids. SREBPs are synthesized as precursor proteins in the endoplasmic reticulum (ER), where they form a complex with another protein, SREBP cleavage activating protein (SCAP). The SCAP molecule contains a sterol sensory domain. In the presence of high cellular sterol concentrations SCAP confines SREBP to the ER. With low cellular concentrations, SCAP escorts SREBP to activation in the Golgi. There, SREBP undergoes two proteolytic cleavage steps to release the mature, biologically active transcription factor, nuclear SREBP (nSREBP). nSREBP translocates to the nucleus and binds to sterol response elements (SRE) in the promoter/enhancer regions of target genes. Additional transcription factors are required to activate transcription of these genes. Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBP-1a and -1c are isoforms produced from a single gene by alternate splicing. SREBP-2 is encoded by a different gene and does not display any isoforms. It appears that SREBPs alone, in the sequence described above, can exert complete control over cholesterol synthesis, whereas many additional factors (hormones, cytokines, etc.) are required for complete control of lipid metabolism. Medicinal manipulation of the SREBP/SCAP system is expected to prove highly beneficial in the management of cholesterol-related disease.展开更多
The internal region of bacterial translocatable IS1 acts as a cis-element to stimulate transcription from the various promoters located upstream. The product of the artA gene is genetically shown to stimulate transcri...The internal region of bacterial translocatable IS1 acts as a cis-element to stimulate transcription from the various promoters located upstream. The product of the artA gene is genetically shown to stimulate transcription with the cis-element. Here, a codon-optimized artA gene was synthesized and cloned to express the ArtA protein. ArtA was purified as the Histagged protein. Nitrocellulose filter binding assay showed that ArtA specifically binds to the IS1 internal region. Electrophoretic mobility shift assay also showed specific binding of ArtA to the IS1 internal region. These results imply that ArtA directly binds to the IS1 internal region and stimulates transcription.展开更多
目的观察拉贝洛尔、硝苯地平联合硫酸镁治疗妊娠高血压的效果及对胰岛素样生长因子-Ⅰ(IGF-Ⅰ)、胰岛素样生长因子-Ⅱ(IGF-Ⅱ)、胰岛素样生长因子结合蛋白-1(IGFBP-1)的影响。方法选取2018年11月至2020年11月福建省立医院南院妇产科收治...目的观察拉贝洛尔、硝苯地平联合硫酸镁治疗妊娠高血压的效果及对胰岛素样生长因子-Ⅰ(IGF-Ⅰ)、胰岛素样生长因子-Ⅱ(IGF-Ⅱ)、胰岛素样生长因子结合蛋白-1(IGFBP-1)的影响。方法选取2018年11月至2020年11月福建省立医院南院妇产科收治的127例妊娠高血压患者,按照随机数表法分为对照组(n=63)和研究组(n=64),对照组使用硝苯地平+硫酸镁治疗,研究组使用拉贝洛尔+硫酸镁治疗,4周后比较两组的血压指标和生化指标,分娩后比较两组的胰岛素样生长因子水平、顺产率、不良结局发生率。结果研究组患者的收缩压(SBP)、舒张压(DBP)低于对照组,差异有统计学意义(P<0.05)。研究组患者的24 h尿蛋白水平(24 h rUprV)、B型钠尿肽(BNP)低于对照组,差异有统计学意义(P<0.05)。研究组产妇的IGF-Ⅰ、IGF-Ⅱ水平高于对照组,IGFBP-1低于对照组,差异有统计学意义(P<0.05)。研究组产妇的顺产率高于对照组,两组的分级数据比较,差异有统计学意义(P<0.05)。研究组的不良结局总发生率低于对照组,差异有统计学意义(P<0.05)。结论拉贝洛尔联合硫酸镁治疗妊娠高血压,有利于降低血压水平,调节胰岛素样生长因子,改善生化指标和妊娠结局,具有更好的临床治疗效果。展开更多
文摘Endothelin-1 and a number of other genes expressd primarily in endothelial cells(EC)require a functional GATA element in their promoter region.The widely expressed zinc finger DNA binding protein GATA-2 has been characterized as the likely GATA factor which binds these GATA elements.To understand the specificity of this interaction,and to investigate the potential for regulation of GATA-2 activity,we have studied translation and post-translational modification of the GATA-2 protein. A specific antiserum immunoprecipitated a 52kDa GATA-2 protein from [35-S] methionine-labeled EC,as well as a wide variety of cultured human cell lines which express GATA-2 mRNA. Immunoprecipitation experiments with [32-P]-orthophosphate labeled cells indicated that GATA-2 is similarly phosphorylated in EC and non-EC lines. Thus the apparent cell-specific activity of this transcription factor is not regulated by translation or phosphorylation, and must derive from the interaction of GATA-2 with other nuclear proteins in the EC.Further studies investigated the potential regulation of GATA-2 phosphorylation in EC. Phosphoamino acid analysis indicated that GATA-2 is phosphorylated on serine and threonine residues in EC.The hasal phosphorylation of GATA-2 was rapidly and markedly increased when EC were treated with calcium ionophore A23187, while phorbol ester and forskolin had no effect.Phosphopeptide map analysis showed that A23187 induced phosphorylation of at least two additional sites in GATA-2.Gel shift assays employing nuclear extracts isolated from EC that had been treated with A23187 had a different DNA binding pattern when compared to control.This regulated phosphorylation of GATA-2 may provide a signaling pathway for hormonal regulation of endothelial cell genes such as endothelin-1 which alter their rate of transcription in response to increased intracellular calcium.
文摘The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane proteins aremembers of the basic helix-loop-helix-leucine zipper (bHLHZip) family of transcription factors. They activate the expression of at least 30 genes involved in the synthesis of cholesterol and lipids. SREBPs are synthesized as precursor proteins in the endoplasmic reticulum (ER), where they form a complex with another protein, SREBP cleavage activating protein (SCAP). The SCAP molecule contains a sterol sensory domain. In the presence of high cellular sterol concentrations SCAP confines SREBP to the ER. With low cellular concentrations, SCAP escorts SREBP to activation in the Golgi. There, SREBP undergoes two proteolytic cleavage steps to release the mature, biologically active transcription factor, nuclear SREBP (nSREBP). nSREBP translocates to the nucleus and binds to sterol response elements (SRE) in the promoter/enhancer regions of target genes. Additional transcription factors are required to activate transcription of these genes. Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBP-1a and -1c are isoforms produced from a single gene by alternate splicing. SREBP-2 is encoded by a different gene and does not display any isoforms. It appears that SREBPs alone, in the sequence described above, can exert complete control over cholesterol synthesis, whereas many additional factors (hormones, cytokines, etc.) are required for complete control of lipid metabolism. Medicinal manipulation of the SREBP/SCAP system is expected to prove highly beneficial in the management of cholesterol-related disease.
文摘The internal region of bacterial translocatable IS1 acts as a cis-element to stimulate transcription from the various promoters located upstream. The product of the artA gene is genetically shown to stimulate transcription with the cis-element. Here, a codon-optimized artA gene was synthesized and cloned to express the ArtA protein. ArtA was purified as the Histagged protein. Nitrocellulose filter binding assay showed that ArtA specifically binds to the IS1 internal region. Electrophoretic mobility shift assay also showed specific binding of ArtA to the IS1 internal region. These results imply that ArtA directly binds to the IS1 internal region and stimulates transcription.
文摘目的观察拉贝洛尔、硝苯地平联合硫酸镁治疗妊娠高血压的效果及对胰岛素样生长因子-Ⅰ(IGF-Ⅰ)、胰岛素样生长因子-Ⅱ(IGF-Ⅱ)、胰岛素样生长因子结合蛋白-1(IGFBP-1)的影响。方法选取2018年11月至2020年11月福建省立医院南院妇产科收治的127例妊娠高血压患者,按照随机数表法分为对照组(n=63)和研究组(n=64),对照组使用硝苯地平+硫酸镁治疗,研究组使用拉贝洛尔+硫酸镁治疗,4周后比较两组的血压指标和生化指标,分娩后比较两组的胰岛素样生长因子水平、顺产率、不良结局发生率。结果研究组患者的收缩压(SBP)、舒张压(DBP)低于对照组,差异有统计学意义(P<0.05)。研究组患者的24 h尿蛋白水平(24 h rUprV)、B型钠尿肽(BNP)低于对照组,差异有统计学意义(P<0.05)。研究组产妇的IGF-Ⅰ、IGF-Ⅱ水平高于对照组,IGFBP-1低于对照组,差异有统计学意义(P<0.05)。研究组产妇的顺产率高于对照组,两组的分级数据比较,差异有统计学意义(P<0.05)。研究组的不良结局总发生率低于对照组,差异有统计学意义(P<0.05)。结论拉贝洛尔联合硫酸镁治疗妊娠高血压,有利于降低血压水平,调节胰岛素样生长因子,改善生化指标和妊娠结局,具有更好的临床治疗效果。
