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101.
We studied fluorescence resonance energy transfer between donors and acceptors bound to double-helical DNA. The donor Hoechst 33258 binds to the minor groove of DNA and the acceptor propidium iodide (PI) is an intercalator. The time-resolved donor decays were measured in the frequency domain. The donor decays were consistent with a random 1-dimensional distribution of acceptors. The decays were analyzed in terms of three 1-dimensional models: a random continuous acceptor distribution; acceptors placed on discrete lattice sites; and a cylindrical model with the acceptor in the center, and the donors on a cylinder surface. The data were well described by all three models. Interpretation in terms of continuous distribution of acceptors revealed a minimum donor to acceptor distance of 13 A, which is 3 bp from the center of Hoechst 33252. These results suggest that PI is excluded from the 4 bp covered by Hoechst 33252 when it is bound to the minor groove of DNA. 相似文献
102.
103.
iNOS expression inhibits hypoxia-inducible factor-1 activity 总被引:11,自引:0,他引:11
Hypoxia-inducible factor-1 (HIF-1) activates genes important in vascular function such as vascular endothelial growth factor (VEGF), erythropoietin (EPO), and inducible nitric oxide synthase (iNOS). iNOS catalyzes the synthesis of nitric oxide (NO), a free radical gas that mediates a number of cellular processes, including regulation of gene expression, vasodilatation, and neurotransmission. Here we demonstrate that iNOS expression inhibits HIF-1 activity under hypoxia in C6 glioma cells transfected with an iNOS gene and a VEGF promoter-driven luciferase gene. HIF-1 induction of VEGF-luciferase activity in C6 cell is also inhibited by sodium nitroprusside (SNP). Furthermore, pretreatment of C6 cells with N-acetyl-l-cysteine (NAC), an antioxidant, nullified the inhibitory effect of iNOS on HIF-1 binding. These results demonstrate that NO generated by iNOS expression inhibits HIF-1 activity in hypoxic C6 cells and suggest a negative feedback loop in the HIF-1 --> iNOS cascade. 相似文献
104.
Nam-On Ku Sara A. Michie Roy M. Soetikno Evelyn Z. Resurreccion Rosemary L. Broome M. Bishr Omary 《The Journal of cell biology》1998,143(7):2023-2032
Simple epithelia express keratins 8 (K8) and 18 (K18) as their major intermediate filament (IF) proteins. One important physiologic function of K8/18 is to protect hepatocytes from drug-induced liver injury. Although the mechanism of this protection is unknown, marked K8/18 hyperphosphorylation occurs in association with a variety of cell stresses and during mitosis. This increase in keratin phosphorylation involves multiple sites including human K18 serine-(ser)52, which is a major K18 phosphorylation site. We studied the significance of keratin hyperphosphorylation and focused on K18 ser52 by generating transgenic mice that overexpress a human genomic K18 ser52→ ala mutant (S52A) and compared them with mice that overexpress, at similar levels, wild-type (WT) human K18. Abrogation of K18 ser52 phosphorylation did not affect filament organization after partial hepatectomy nor the ability of mouse livers to regenerate. However, exposure of S52A-expressing mice to the hepatotoxins, griseofulvin or microcystin, which are associated with K18 ser52 and other keratin phosphorylation changes, resulted in more dramatic hepatotoxicity as compared with WT K18-expressing mice. Our results demonstrate that K18 ser52 phosphorylation plays a physiologic role in protecting hepatocytes from stress-induced liver injury. Since hepatotoxins are associated with increased keratin phosphorylation at multiple sites, it is likely that unique sites aside from K18 ser52, and phosphorylation sites on other IF proteins, also participate in protection from cell stress. 相似文献
105.
106.
1-Thio-beta-D-galactofuranosides: synthesis and evaluation as beta-D- galactofuranosidase inhibitors
Marino C; Marino K; Miletti L; Manso Alves MJ; Colli W; de Lederkremer RM 《Glycobiology》1998,8(9):901-904
Beta-D-galactofuranosidase is a good chemotherapeutic target for the design
of inhibitors, since beta-D-galactofuranose is a constituent of important
parasite glycoconjugates but is not present in the host mammals. With this
aim, we have synthesized for the first time alkyl, benzyl and aryl
1-thio-beta-D-galactofuranosides by condensation of
penta-O-benzoyl-alpha,beta-D-galactofuranose with the corresponding thiols,
in the presence of SnCl4as catalyst. The complete chemical and
spectroscopical characterization of these compounds showed that the
reaction was stereoselective. Debenzoylation with sodium methoxide afforded
the beta-S-galactofuranosides in high yield. The thioglycosides were tested
as inhibitors of the beta-D- galactofuranosidase of Penicillium fellutanum,
using for the first time 4-nitrophenyl-beta-D-galactofuranoside as
chromogenic substrate. The 4- aminophenyl-1-thio-beta-D-galactofuranoside,
obtained by catalytic hydrogenation of the nitrophenyl derivative, was the
best inhibitor being then an adequate ligand for the preparation of an
affinity phase aimed at the isolation of beta-d-galactofuranosidases from
different sources. Also the inhibitory activity of d-galactono-1, 4-lactone
was shown.
相似文献
107.
Phosphorylation of human keratin 18 serine 33 regulates binding to 14-3-3 proteins. 总被引:19,自引:0,他引:19
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Members of the 14-3-3 protein family bind the human intermediate filament protein keratin 18 (K18) in vivo, in a cell-cycle- and phosphorylation-dependent manner. We identified K18 Ser33 as an interphase phosphorylation site, which increases its phosphorylation during mitosis in cultured cells and regenerating liver, and as an in vitro cdc2 kinase phosphorylation site. Comparison of wild-type versus K18 Ser33-->Ala/Asp transfected cells showed that K18 Ser33 phosphorylation is essential for the association of K18 with 14-3-3 proteins, and plays a role in keratin organization and distribution. Mutation of another K18 major phosphorylation site (Ser52) or K18 glycosylation sites had no effect on the binding of K18 to 14-3-3 proteins. The K18 phospho-Ser33 motif is different from several 14-3-3-binding phosphomotifs already described. Antibodies that are specific to K18 phospho-Ser33 or phospho-Ser52 show that although Ser52 and Ser33 phosphorylated K18 molecules manifest partial colocalization, these phosphorylation events reside predominantly on distinct K18 molecules. Our results demonstrate a unique K18 phosphorylation site that is necessary but not sufficient for K18 binding to 14-3-3 proteins. This binding is likely to involve one or more mitotic events coupled to K18 Ser33 phosphorylation, and plays a role in keratin subcellular distribution. Physiological Ser52 or Ser33 phosphorylation on distinct K18 molecules suggests functional compartmentalization of these modifications. 相似文献
108.
Eun-Kyung Yoon Sae-Kwang Ku Wonhwa Lee Soyoung Kwak Hyejin Kang Byeongjin Jung Jong-Sup Bae 《BMB reports》2015,48(10):577-582
Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain. Here, the anticoagulant effects of scolymoside, an active compound in C. subternata, were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of thrombin and activated factor X (FXa). The effects of scolymoside on plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) expression were evaluated in tumor necrosis factor (TNF)-α-activated human endothelial cells. Treatment with scolymoside resulted in prolonged aPTT and PT and the inhibition of thrombin and FXa activities and production. In addition, scolymoside inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. Scolymoside also elicited anticoagulant effects in mice, including a significant reduction in the PAI-1 to t-PA ratio. Collectively, these findings indicate that scolymoside possesses anticoagulant activities and could be developed as a novel anticoagulant. [BMB Reports 2015; 48(10): 577-582] 相似文献
109.
Dae Won Kim Sung Ho Lee Min Jea Shin Kibom Kim Sae Kwang Ku Jong Kyu Youn Su Bin Cho Jung Hwan Park Chi Hern Lee Ora Son Eun Jeong Sohn Sung-Woo Cho Jong Hoon Park Hyun Ah Kim Kyu Hyung Han Jinseu Park Won Sik Eum Soo Young Choi 《BMB reports》2015,48(11):618-623
FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI. [BMB Reports 2015; 48(11): 618-623] 相似文献
110.
Kate?ina Ku?elová Barbora Brodská Ota Fuchs Marie Dobrovolná Petr Soukup Petr Cetkovsky 《PloS one》2015,10(5)
Nucleophosmin 1 (NPM1) mutations are frequently found in patients with acute myeloid leukemia (AML) and the newly generated sequences were suggested to induce immune response contributing to the relatively favorable outcome of patients in this AML subset. We hypothesized that if an efficient immune response against mutated nucleophosmin can be induced in vivo, the individuals expressing HLA alleles suitable for presenting NPM-derived peptides should be less prone to developing AML associated with NPM1 mutation. We thus compared HLA class I frequencies in a cohort of patients with mutated NPM1 (63 patients, NPMc+), a cohort of patients with wild-type NPM1 (94 patients, NPMwt) and in normal individuals (large datasets available from Allele Frequency Net Database). Several HLA allelic groups were found to be depleted in NPMc+ patients, but not in NPMwt compared to the normal distribution. The decrease was statistically significant for HLA B*07, B*18, and B*40. Furthermore, statistically significant advantage in the overall survival was found for patients with mutated NPM1 expressing at least one of the depleted allelic groups. The majority of the depleted alleles were predicted to bind potent NPM-derived immunopeptides and, importantly, these peptides were often located in the unmutated part of the protein. Our analysis suggests that individuals expressing specific HLA allelic groups are disposed to develop an efficient anti-AML immune response thanks to aberrant cytoplasmic localization of the mutated NPM protein. 相似文献