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排序方式: 共有58条查询结果,搜索用时 31 毫秒
1.
Hoe 140 abolishes the blood pressure lowering effect of taurine in high fructose-fed rats 总被引:1,自引:0,他引:1
Summary. High fructose feeding induces moderate increases in blood pressure of normal rats, associated with hyperinsulinemia, insulin resistance and impaired glucose tolerance. Increased vascular resistance, and sodium retention have been proposed to contribute to the blood pressure elevation in this model. Taurine, a sulphur-containing amino acid has been reported to have antihypertensive and antinatriuretic actions. In addition, taurine is shown to increase the excretion of nitrite and kinin availability and hence would be expected to improve the vascular tone. In the present study, the involvement of kinins in the blood pressure lowering effect of taurine was investigated by coadministration of Hoe 140, a kinin B2 receptor antagonist along with taurine. The effects of taurine on plasma and urinary concentrations of sodium and tissue kallikrein activity were studied in high fructose-fed rats. Fructose-fed rats had elevated blood pressure and decreased levels of sodium in urine. Treatment with 2% taurine in drinking water prevented the blood pressure elevation and coadministration of Hoe 140 abolished this effect of taurine in high fructose-fed rats. The findings confirm the antinatriuretic action of taurine and also suggest a role for the kinins in the mechanism of taurine action in diet-induced hypertension. 相似文献
2.
Krauchenco S Pando SC Marangoni S Polikarpov I 《Biochemical and biophysical research communications》2003,312(4):1303-1308
The three-dimensional structure of a novel Kunitz (STI) family member, an inhibitor purified from Delonix regia seeds (DrTI), was solved by molecular replacement method and refined, respectively, to R(factor) and R(free) values of 21.5% and 25.3% at 1.75A resolution. The structure has a classical beta-trefoil fold, however, differently from canonical Kunitz type (STI) inhibitors, its reactive site loop has an insertion of one residue, Glu68, between the residues P1 and P2. Surprisingly, DrTI is an effective inhibitor of trypsin and human plasma kallikrein, but not of chymotrypsin and tissue kallikrein. Putative structural grounds of such specificity are discussed. 相似文献
3.
人组织激肽释放酶基因家族由KLK1-KLK15构成,编码一组丝氨酸蛋白酶。研究发现KLK基因家族涉及癌细胞的多种生物学功能,且其表达受类固醇激素的调节。人组织激肽释放酶4是丝氨酸蛋白酶家族的一个成员,在多种激素依赖性肿瘤如卵巢癌、前列腺癌、乳腺癌、子宫内膜癌中高表达,且表达量受雌激素、孕激素、雄激素不同程度的调节。近年来很多文献报道人组织激肽释放酶4涉及癌细胞的增殖、上皮间质转化及细胞外基质的降解等过程,可能促进了肿瘤的发生、发展,且与激素依赖性肿瘤的预后不良有关。这些研究显示人组织激肽释放酶4与激素依赖性肿瘤关系密切,是其潜在的肿瘤标记物和治疗靶点,随着研究的进一步深入,有望应用于激素依赖性肿瘤的早期诊断、病程监测和治疗。 相似文献
4.
《Journal of biological education》2012,46(4):245-246
The kidney is traditionally regarded as an exocrine gland, producing urine to regulate body fluid volumes and composition and to excrete nitrogenous wastes. In addition to these functions, it is now recognized that a number of hormones are produced within the kidney that have local and systemic actions. These hormones and hormonal cascades include the renin-angiotensin and kallikrein-kinin systems, production of calcitriol, erythropoietin and prostaglandins. These hormones act to influence inter alia blood pressure, sodium and water excretion, red blood cell production, calcium homeostasis and the immune system. 相似文献
5.
Objectives
Amelogenesis imperfecta, dentinogenesis imperfecta, and dentin dysplasia are the most common non-syndromic dental disorders. In this study, we analysed and localised the gene(s) responsible for inherited non-syndromic dental disorders in a Chinese family.Methods
This study identified and researched non-syndromic dental disorders in a four-generation Chinese family, including four affected individuals whose clinical phenotype was atypical. Linkage analysis with seven polymorphic markers that localise to six different autochromosomes showed that the family was linked through chromosome 4q. All exons and exon–intron boundaries of dentin sialophosphoprotein (DSPP), enamelin (ENAM), and ameloblastin (AMBN), which are located on chromosome 4q, were sequenced in nine of the family members.Results
Direct DNA sequence analysis revealed the existence of a G to A transversion in exon 4 (g.13081786G > A, c.727G > A, p.Asp243Asn, based on reference sequences NM_014208.3) of the DSPP gene, and this sequence variation correlated exactly with the presence of the disease.Conclusion
These results indicate that mutation p.Asp243Asn is a highly probable cause of non-syndromic dental disorder in this Chinese family. The presence of symptom heterogeneity is possible, as the clinical classification system is hampered by the lack of close correlation between the subtype and the molecular defect. 相似文献6.
Balan V Nangia-Makker P Kho DH Wang Y Raz A 《The Journal of biological chemistry》2012,287(8):5192-5198
Galectin-3 is a chimeric carbohydrate-binding protein, which interacts with cell surface carbohydrate-containing molecules and extracellular matrix glycoproteins and has been implicated in various biological processes such as cell growth, angiogenesis, motility, and metastasis. It is expressed in a wide range of tumor cells and is associated with tumor progression. The functions of galectin-3 are dependent on its localization and post-translational modifications such as cleavage and phosphorylation. Recently, we showed that galectin-3 Tyr-107 is phosphorylated by c-Abl; concomitantly, it was also shown that galectin-3 can be cleaved at this site by prostate-specific antigen (PSA), a chymotrypsin-like serine protease, after Tyr-107, resulting in loss of galectin-3 multivalency while preserving its carbohydrate binding activity. Galectin-3 is largely a monomer in solution but may form a homodimer by self-association through its carbohydrate recognition domain, whereas, in the presence of a ligand, galectin-3 polymerizes up to pentamers utilizing its N-terminal domain. Oligomerization is a unique feature of secreted galectin-3, which allows its function by forming ordered galectin-glycan structures, i.e. lattices, on the cell surface or through direct engagement of specific cell surface glycoconjugates by traditional ligand-receptor binding. We questioned whether Tyr-107 phosphorylation by c-Abl affects galectin-3 cleavage by PSA. The data suggest a role for galectin-3 in prostate cells associated with increased activity of c-Abl kinase and loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) activity. In addition, the ratio of phosphorylated/dephosphorylated galectin-3 might be used as a complementary value to that of PSA for prognosis of prostate cancer and a novel therapeutic target for the treatment of prostate cancer. 相似文献
7.
de Cássia Dias S Sakauchi D Abreu PA de Lima Netto S Iourtov D Raw I Kubrusly FS 《Biotechnology letters》2008,30(5):807-812
Aprotinin, the most studied serine proteinase inhibitor, was isolated from porcine lung for the first time. The purified porcine
aprotinin had an Mr value of ∼7 kDa. It cross-reacted with polyclonal serum anti-commercial aprotinin. About 1 μg porcine
aprotinin inhibited 6 μg trypsin whereas 1 μg commercial soybean inhibitor inhibited only 1 μg trypsin. The aprotinin gene
was also isolated from porcine lung: the deduced amino acid sequence showed 74% identity to bovine aprotinin. 相似文献
8.
Julie Chao Lee Chao Harry S. Margolius 《Biochimica et Biophysica Acta (BBA)/General Subjects》1984,801(2):244-249
Rat spleen kallikrein was identified and purified by DEAE-cellulose and monoclonal antibody-affinity chromatography. The purified enzyme has Tos-Arg-OMe esterase activity and kinin-releasing activity from a purified low-molecular-weight kininogen substrate. In the direct radioimmunoassay for tissue kallikrein, the splenic enzyme displays parallelism with standard curves of rat urinary kallikrein. The pH profiles of the Tos-Arg-OMe esterase activities of spleen and urinary kallikrein were identical with optima at 9.0 Rat spleen kallikrein was inhibited strongly by aprotinin and affinity-purified kallikrein antibody and weakly by soybean trypsin inhibitor. The IC50 values were similar to those observed against rat urinary kallikrein. Neither the urinary nor the splenic enzyme was inhibited by lima bean trypsin inhibitor or preimmune serum immunoglobulins. Spleen kallikrein was labeled with [14]diisopropylphosphorofluoridate and visualized by fluorography on a sodium dodecyl sulfate-polyacrylamide gel. The electrophoretic mobility of the splenic enzyme was indistinguishable from that of urinary kallikrein A with an estimated Mr of approx. 38 000. With Western blot analyses using a rabbit anti-kallikrein antibody followed by 125I-labeled protein A binding, the spleen and urinary kallikreins were again visualized at identical positions by autoradiography. The data show that there is a rat splenic tissue kallikrein which is indistinguishable from a renal kallikrein with respect to physicochemical properties, immunological character and susceptibility to inhibitors. 相似文献
9.
Sayli Dalal Anil Mhashal Narendra Kadoo 《Journal of biomolecular structure & dynamics》2017,35(2):330-342
Kallikrein, a physiologically vital serine protease, was investigated for its functional and conformational transitions during chemical (organic solvents, Gdn-HCl), thermal, and pH induced denaturation using biochemical and biophysical techniques and molecular dynamics (MD) simulations approach. The enzyme was exceptionally stable in isopropanol and ethanol showing 110% and 75% activity, respectively, after 96 h, showed moderate tolerance in acetonitrile (45% activity after 72 h) and much lower stability in methanol (40% activity after 24 h) (all the solvents [90% v/v]). Far UV CD and fluorescence spectra indicated apparent reduction in compactness of KLKp structure in isopropanol system. MD simulation studies of the enzyme in isopropanol revealed (1) minimal deviation of the structure from native state (2) marginal increase in radius of gyration and solvent accessible surface area (SASA) of the protein and the active site, and (3) loss of density barrier at the active site possibly leading to increased accessibility of substrate to catalytic triad as compared to methanol and acetonitrile. Although kallikrein was structurally stable up to 90 °C as indicated by secondary structure monitoring, it was functionally stable only up to 45 °C, implicating thermolabile active site geometry. In GdnHCl [1.0 M], 75% of the activity of KLKp was retained after incubation for 4 h, indicating its denaturant tolerance. A molten globule-like structure of KLKp formed at pH 1.0 was more thermostable and exhibited interesting structural transitions in organic solvents. The above results provide deeper understanding of functional and structural stability of the serine proteases at molecular level. 相似文献
10.
Wolfgang Skala Daniel T. Utzschneider Viktor Magdolen Mekdes Debela Shihui Guo ) Charles S. Craik Hans Brandstetter Peter Goettig 《The Journal of biological chemistry》2014,289(49):34267-34283
Human kallikrein-related peptidase 2 (KLK2) is a tryptic serine protease predominantly expressed in prostatic tissue and secreted into prostatic fluid, a major component of seminal fluid. Most likely it activates and complements chymotryptic KLK3 (prostate-specific antigen) in cleaving seminal clotting proteins, resulting in sperm liquefaction. KLK2 belongs to the “classical” KLKs 1–3, which share an extended 99- or kallikrein loop near their non-primed substrate binding site. Here, we report the 1.9 Å crystal structures of two KLK2-small molecule inhibitor complexes. In both structures discontinuous electron density for the 99-loop indicates that this loop is largely disordered. We provide evidence that the 99-loop is responsible for two biochemical peculiarities of KLK2, i.e. reversible inhibition by micromolar Zn2+ concentrations and permanent inactivation by autocatalytic cleavage. Indeed, several 99-loop mutants of KLK2 displayed an altered susceptibility to Zn2+, which located the Zn2+ binding site at the 99-loop/active site interface. In addition, we identified an autolysis site between residues 95e and 95f in the 99-loop, whose elimination prevented the mature enzyme from limited autolysis and irreversible inactivation. An exhaustive comparison of KLK2 with related structures revealed that in the KLK family the 99-, 148-, and 220-loop exist in open and closed conformations, allowing or preventing substrate access, which extends the concept of conformational selection in trypsin-related proteases. Taken together, our novel biochemical and structural data on KLK2 identify its 99-loop as a key player in activity regulation. 相似文献