心血管疾病的核因子-κB活化及其意义

核因子－κＢ是一种可调控多种细胞基因表达的重要转录因子，参与了多种心血管疾病的病理生理进程。在适当情况下抑制核因子－κＢ的活化，可望为心血管疾病开辟新的治疗途径。     

心血管疾病的核因子-кB活化及其意义

核因子-κB是一种可调控多种细胞基因表达的重要转录因子参与了多种心血管疾病的病理生理进程.在适当情况下抑制核因子-κB的活化可望为心血管疾病开辟新的治疗途径.     

小泛素样修饰蛋白4和糖尿病相关研究

小泛素样修饰蛋白(SUMO)4是SUMO家族中新近发现的成员.SUMO的生化反应途径与泛素化有类似之处,但不同的是会使蛋白质更加稳定.而不是降解蛋白质.SUM04可能是通过核因子(NF)-kB调控机制产生作用,拮抗泛素对NF-kB抑制蛋白(IkB)α的作用.而SUM04 M55V变异可能导致SUMO化失效,泛素系统和NF-kB激活,介导免疫反应和炎性反应.并且已经得到证实的是,SUM04基因M55V的多态性与某些人群的1型糖尿病相关.现在正在进行的一些研究试图揭示其在2型精尿病发病机制中的作用.     

小泛素样修饰蛋白4和糖尿病相关研究

小泛素样修饰蛋白(SUMO)4是SUMO家族中新近发现的成员.SUMO的生化反应途径与泛素化有类似之处,但不同的是会使蛋白质更加稳定.而不是降解蛋白质.SUM04可能是通过核因子(NF)-kB调控机制产生作用,拮抗泛素对NF-kB抑制蛋白(IkB)α的作用.而SUM04 M55V变异可能导致SUMO化失效,泛素系统和NF-kB激活,介导免疫反应和炎性反应.并且已经得到证实的是,SUM04基因M55V的多态性与某些人群的1型糖尿病相关.现在正在进行的一些研究试图揭示其在2型精尿病发病机制中的作用.     

小泛素样修饰蛋白4和糖尿病相关研究

小泛素样修饰蛋白(SUMO)4是SUMO家族中新近发现的成员.SUMO的生化反应途径与泛素化有类似之处,但不同的是会使蛋白质更加稳定.而不是降解蛋白质.SUM04可能是通过核因子(NF)-kB调控机制产生作用,拮抗泛素对NF-kB抑制蛋白(IkB)α的作用.而SUM04 M55V变异可能导致SUMO化失效,泛素系统和NF-kB激活,介导免疫反应和炎性反应.并且已经得到证实的是,SUM04基因M55V的多态性与某些人群的1型糖尿病相关.现在正在进行的一些研究试图揭示其在2型精尿病发病机制中的作用.     

小泛素样修饰蛋白4和糖尿病相关研究

小泛素样修饰蛋白(SUMO)4是SUMO家族中新近发现的成员.SUMO的生化反应途径与泛素化有类似之处,但不同的是会使蛋白质更加稳定.而不是降解蛋白质.SUM04可能是通过核因子(NF)-kB调控机制产生作用,拮抗泛素对NF-kB抑制蛋白(IkB)α的作用.而SUM04 M55V变异可能导致SUMO化失效,泛素系统和NF-kB激活,介导免疫反应和炎性反应.并且已经得到证实的是,SUM04基因M55V的多态性与某些人群的1型糖尿病相关.现在正在进行的一些研究试图揭示其在2型精尿病发病机制中的作用.     

小泛素样修饰蛋白4和糖尿病相关研究

小泛素样修饰蛋白(SUMO)4是SUMO家族中新近发现的成员.SUMO的生化反应途径与泛素化有类似之处,但不同的是会使蛋白质更加稳定.而不是降解蛋白质.SUM04可能是通过核因子(NF)-kB调控机制产生作用,拮抗泛素对NF-kB抑制蛋白(IkB)α的作用.而SUM04 M55V变异可能导致SUMO化失效,泛素系统和NF-kB激活,介导免疫反应和炎性反应.并且已经得到证实的是,SUM04基因M55V的多态性与某些人群的1型糖尿病相关.现在正在进行的一些研究试图揭示其在2型精尿病发病机制中的作用.     

小泛素样修饰蛋白4和糖尿病相关研究

小泛素样修饰蛋白(SUMO)4是SUMO家族中新近发现的成员.SUMO的生化反应途径与泛素化有类似之处,但不同的是会使蛋白质更加稳定.而不是降解蛋白质.SUM04可能是通过核因子(NF)-kB调控机制产生作用,拮抗泛素对NF-kB抑制蛋白(IkB)α的作用.而SUM04 M55V变异可能导致SUMO化失效,泛素系统和NF-kB激活,介导免疫反应和炎性反应.并且已经得到证实的是,SUM04基因M55V的多态性与某些人群的1型糖尿病相关.现在正在进行的一些研究试图揭示其在2型精尿病发病机制中的作用.     

小泛素样修饰蛋白4和糖尿病相关研究

小泛素样修饰蛋白(SUMO)4是SUMO家族中新近发现的成员.SUMO的生化反应途径与泛素化有类似之处,但不同的是会使蛋白质更加稳定.而不是降解蛋白质.SUM04可能是通过核因子(NF)-kB调控机制产生作用,拮抗泛素对NF-kB抑制蛋白(IkB)α的作用.而SUM04 M55V变异可能导致SUMO化失效,泛素系统和NF-kB激活,介导免疫反应和炎性反应.并且已经得到证实的是,SUM04基因M55V的多态性与某些人群的1型糖尿病相关.现在正在进行的一些研究试图揭示其在2型精尿病发病机制中的作用.     

小泛素样修饰蛋白4和糖尿病相关研究

小泛素样修饰蛋白(SUMO)4是SUMO家族中新近发现的成员.SUMO的生化反应途径与泛素化有类似之处,但不同的是会使蛋白质更加稳定.而不是降解蛋白质.SUM04可能是通过核因子(NF)-kB调控机制产生作用,拮抗泛素对NF-kB抑制蛋白(IkB)α的作用.而SUM04 M55V变异可能导致SUMO化失效,泛素系统和NF-kB激活,介导免疫反应和炎性反应.并且已经得到证实的是,SUM04基因M55V的多态性与某些人群的1型糖尿病相关.现在正在进行的一些研究试图揭示其在2型精尿病发病机制中的作用.     

Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats

The aim of this study was to investigate whether glucocorticoid administration had a beneficial effect on serum concentrations of insulin-like growth factor I (IGF-I) and on IGF-binding protein 3 (IGFBP-3) in rats injected with lipopolysaccharide (LPS). Adult male rats were injected with LPS or saline and pretreated with dexamethasone or saline. Dexamethasone administration decreased growth hormone (GH) receptor and IGF-I mRNA levels in the liver of control rats. LPS decreased GH receptor and IGF-I gene expression in the liver of saline-treated rats but not in the liver of dexamethasone-pretreated rats. In the kidney, GH receptor mRNA levels were not modified by dexamethasone or LPS treatment. However, LPS decreased renal IGF-I gene expression and dexamethasone pretreatment prevented this decrease. Serum concentrations of IGF-I were decreased by LPS, and dexamethasone pretreatment attenuated this effect. The gene expression of IGFBP-3 in the liver and kidney and its circulating levels were decreased by LPS. In control rats dexamethasone increased circulating IGFBP-3 and its gene expression in the liver, and decreased the proteolysis of this protein. Dexamethasone pretreatment attenuated the LPS-induced decrease in IGFBP-3 gene expression in the liver and prevented the LPS-induced decrease in IGFBP-3 gene expression in the kidney. Moreover, dexamethasone pretreatment attenuated the LPS-induced decrease in serum concentrations of IGFBP-3 and decreased the LPS-induced IGFBP-3 proteolysis in serum. In conclusion, dexamethasone pretreatment partially attenuates the inhibitory effect of LPS on serum IGF-I by blocking the decrease of its gene expression in the kidney as well as by attenuating the decrease in serum concentrations of IGFBP-3.     

Differential DNase I sensitivity of the albumin and alpha-fetoprotein genes in chromatin from rat tissues and cell lines.

We have examined the DNase I sensitivity of the albumin and alpha-fetoprotein (AFP) genes in different rat tissues (adult liver and kidney) and cloned cell lines (hepatoma 7777-C8, JF1 fibroblasts), which show drastic differences in the level of expression of these two genes. This was done by studying the disappearance of defined restriction endonuclease fragments of these genes as a function of limited DNase I digestion. The sensitivity of these genes was compared to that of a gene not expressed in the hepatic cells and to that of a ubiquitously expressed gene. In nuclei from adult rat liver the albumin and AFP genes were preferentially degraded by the nucleolytic action of DNase I, whereas they were not in rat kidney nuclei. In the hepatoma cells the AFP gene was much more sensitive to DNase I digestion than the albumin gene; both genes were very resistant to DNase I action in fibroblastic nuclei. When analyzed in relation to the level of gene expression our results indicate that alterations in the chromatin structure of the albumin and AFP genes might be involved in the early establishment of the tissue-specific potential of overt gene expression; such alterations reflected in an altered DNase I sensitivity do not appear to be responsible for the changes in gene activity occurring during the terminal differentiation of the hepatocyte; and modifications in the chromatin structure of these genes might occur during oncogenic events; these structural modifications could be related to the changes in gene expression observed in hepatocarcinogenic processes.     

PRKX,a phylogenetically and functionally distinct cAMP-dependent protein kinase,activates renal epithelial cell migration and morphogenesis

The human protein kinase X gene (PRKX) is a member of an ancient family of cAMP-dependent serine/threonine kinases here shown to be phylogenetically distinct from the classical PKA, PKB/Akt, PKC, SGK, and PKG gene families. Renal expression of the PRKX gene is developmentally regulated and restricted to the ureteric bud epithelium of the fetal metanephric kidney. Aberrant adult kidney expression of PRKX was found in autosomal dominant polycystic kidney disease. PRKX kinase expression markedly activated migration of cultured renal epithelial cells in the presence of cAMP; this effect was blocked by cell treatment with the PKA inhibitor H89 and was not observed in PKA-transfected cells. In addition, expression of PRKX kinase activated branching morphogenesis of Madin-Darby canine kidney cells in collagen gels even in the absence of cAMP and/or hepatocyte growth factor, an effect not seen with either PKA expression or expression of a mutant, kinase-inactivated PRKX. These results suggest that the PRKX kinase may regulate epithelial morphogenesis during mammalian kidney development. Because another member of the PRKX gene family (the Dictyostelium discoideum gene KAPC-DICDI) also plays a role in cellular migration, these studies suggest that regulation of morphogenesis may be a distinctive property of these genes that has been conserved in evolution that is not shared with PKA family genes.     

Regulation of human erythropoietin gene induction by upstream flanking sequences in transgenic mice

Human erythropoietin (Epo) gene expression is inducible by hypoxia or anaemia in the kidney and liver. Previous transgenic mouse experiments have demonstrated that sequences required for Epo gene induction in the kidney reside in a 7.8 kb Bam HI fragment located 6 kb upstream of the gene. To sublocalize these sequences, we performed Desoxyribonuclease I (DNAse I) mapping studies using transgenic mice which carried this DNA fragment. These studies revealed a DNAse I hypersensitive site (DNAse I HS) located 4.6 kb from the upstream end of the 7.8 kb fragment in anaemic kidney and liver samples. Sequence analysis of the region encompassing the DNAse I HS revealed an element with remarkable homology to the 3' Epo gene hypoxia-inducible enhancer. This suggested the presence of an additional regulatory element that contributes to the control of hypoxia-inducible Epo gene expression in kidney and liver. We constructed transgenic mice containing the human Epo gene linked to either the 5 kb upstream or 2.5 kb downstream portion of the 7.8 kb fragment. Inducible expression was limited to the liver. Thus, neither fragment was alone sufficient to confer kidney inducible expression. These findings indicate that sequences more than 8.5 kb upstream of the Epo gene are required for kidney-specific induction. They suggest that either those sequences reside in an 0.3 kb Hind III fragment located between the 5 kb and the 2.5 kb fragments or that sequences in the 5 kb or 0.3 kb fragments must interact with sequences in the 2.5 kb fragment to allow Epo gene induction in the kidney.     

脂多糖对大鼠不同组织中一氧化氮合成酶基因表达的影响

通过Northernblot和NADPH－心肌黄酶染色显示一氧化氮合成酶活性的组织化学分析方法，观察了脂多糖对大氧心脏、主动脉和肾组织中诱导型一氧化氮合成酶基因表达的影响及诱导型一氧化氮合成酶被脂多糖诱导表达的动力学。结果表明，未经脂多糖处理的大鼠诱导型一氧化氮合成酶基因在所检测的三种组织中表达活性很低，脂多糖作用于大鼠2h，心、肾和主动脉中的诱导型一氧化氮合成酶mRNA开始增加，6h达到峰值，此后，逐渐下降，24h回复到对照水平。一氧化氮合成酶组织化学染色显示，对照大鼠的组织细胞内存在较低的组成型一氧化氮合成酶活性，被脂多糖处理不同时间后，三种组织中的一氧化氮合成酶活性均显著升高，到24h仍维持在较高水平，提示诱导型一氧化氮合成酶被合成后，在组织细胞内较为稳定。     

Kidney renin gene expression in spontaneously hypertensive rats

We studied the expression of kidney renin gene in hypertensive animals by measuring the kidney renin messenger (m) RNA. The kidney renin mRNA was quantified by densitometric Northern blot analysis using a 32P-labelled rat renin genomic DNA fragment as a hybridization probe. Spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) were treated with a low-sodium diet plus furosemide, captopril or propranolol for a week. Plasma renin activity (PRA) in SHR and WKY was increased similarly by sodium depletion and by treatment with captopril. PRA in both strains was not decreased significantly by treatment with propranolol. Both sodium depletion and captopril treatment caused significant increases in the kidney renin mRNA in SHR and WKY. However, the increases in the kidney renin mRNA of SHR were greater than those in the corresponding WKY (SHR, 10.0- and 22.1-fold increases; WKY, 6.2- and 7.8-fold increases, respectively). Propranolol had no effect on the kidney renin gene expression in either WKY or SHR. These results indicate that SHR show an enhanced expression of the renin gene in the kidney compared with WKY in response to stimuli that increase renin release.     

The influence of sex on early stage markers of kidney dysfunction in response to juvenile obesity

Changes within the kidney in response to obesity are critical in determining the magnitude of later dysfunction. However, the cause of this process in response to juvenile onset obesity and how it can be determined by sex is poorly understood. We therefore examined the effect of juvenile obesity induced by exposure to a restricted activity environment from weaning until early adulthood on the molecular responses within the kidney together with glomerular area and nucleated cell number. This was stratified by sex and was undertaken in a sheep model of early obesity. Despite a similar magnitude of increase in fat mass with obesity onset between sexes, adverse effects on glomerular area and cell number together with raised gene expression within the kidney only occurred in males. Irrespective of obesity, gene expression of C-C motif receptor 2 was higher, and interleukin-6 lower, in male kidneys compared with female kidneys. The effects of sex on molecular differences within the kidney were amplified with obesity, which had no effect on any gene studied in females but had an enhanced response in males. Obese males therefore showed increased gene expression of a range of markers relating to the glucocorticoid axis, inflammation, and lipid sensing. In conclusion, young females were protected from adverse renal effects of obesity, which results in very little inflammatory or related responses. Our findings emphasize the critical importance of sex specificity in disease pathogenesis. An increased understanding of the specific mechanisms will have important implications for therapeutic strategies aimed at preventing adverse consequences of obesity.