共查询到20条相似文献,搜索用时 0 毫秒
1.
Penelope Bouziotis Eleni Gourni George Patsis Dimitrios Psimadas Christos Zikos Melpomeni Fani Stavros Xanthopoulos George Loudos Maria Paravatou-Petsotas Evangelia Livaniou Alexandra D. Varvarigou Ioannis Pirmettis Minas Papadopoulos 《Bioorganic & medicinal chemistry》2013,21(21):6699-6707
Bombesin is a neuropeptide widely studied due to its ability to target various types of cancers. Technetium-99m on the other hand is ideal for diagnostic tumor targeting. The aim of the present study is the investigation of the coupling of the ligand (S)-(2-(2′-pyridyl)ethyl)-d,l-cysteine with the BN-peptide Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met(CONH2) through the spacer aminohexanoic acidand the labeling of the resulting derivative MBN with the synthon [M(CO)3(H2O)3]+ (M = 99mTc, Re). The peptide was synthesized according to the SPPS method, purified and characterized by ESI-MS. The new 99mTc-labeled biomolecule was stable in vitro, showed high affinity for the human GRP receptor expressed in PC3 cells and the rate of internalization was found to be time-dependent tissue distribution of the radiopeptide was evaluated in normal mice and in prostate cancer experimental models and significant radioactivity uptake was observed in the pancreas of normal mice as well as in PC3 tumors. Dynamic studies of the radiopeptide showed satisfactory tumor images. 相似文献
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Shubhamoy Chowdhury 《Inorganica chimica acta》2008,361(1):145-152
Oxorhenium(V) complexes with ‘3+1’ mixed ligands, [ReO(SSS)L], where SSS is η3-(SCH2CH2SCH2CH2S), L = η1-(C6H4COOH-4-S), η1-(C6H4CONHCH2COOEt-4-S), η1-(C6H4CONHCH(CH3)COOEt-4-S), and η1-(C6H4CONHCH(CH2Ph)COOEt-4-S), have been synthesized. These L ligands and [ReO(SSS)L] complexes were characterized by IR, 1H NMR, 13C NMR, and MAS spectrometers. Molecular structure of [ReO(SSS){η1-(C6H4COOH-4-S)}] complex was determined to be a distorted square pyramidal by single crystal X-ray analytical method. 相似文献
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目的:研究重组人粒细胞集落刺激因子(rhG-CSF)动员对供者CD4+T细胞表面分子淋巴细胞功能相关抗原-1(LFA-1)、细胞间黏附分子-1(ICAM-1)、L-选择素(LAM-1)和人整合素-4(VLA-4)的表达及其介导的CD4+T细胞功能的影响,探讨外周血干细胞移植过程中CD4+T细胞免疫耐受机制。方法:使用三色荧光标记检测动员前及动员后第5天供者外周血LFA-1、ICAM-1、LAM-1和VLA-4的表达率,ELISA方法检测动员前后CD4+T细胞分泌IFN-γ和IL-4能力,免疫磁性分选法分离纯化CD4+T细胞,检测动员前后CD4+T细胞对基质细胞衍生因子-1α(SDF-1α)的迁移能力和对ICAM-1的黏附能力。结果:动员前后CD4+T细胞LFA-1(CD11a)和VLA-4(CD49d)表达率差异无统计学意义(P>0.01),动员前后CD4+T细胞LAM-1(CD62L)和ICAM-1(CD54)的表达率差异均有统计学意义,动员前显著高于动员后(P<0.01);动员前后CD4+T淋巴细胞向SDF-1α的迁移率差异无统计学意义(P>0.01);动员后CD4+T细胞对ICAM-1的黏附率降低(P<0.01);动员后IL-4和IFN-γ两个细胞因子在外周血血清的浓度均降低(P<0.01)。结论:rhG-CSF动员不影响CD4+T细胞LFA-1和VLA-4表达及CD4+T细胞迁移,但影响CD4+T细胞ICAM-1和LAM-1表达以及CD4+T细胞通过LFA-1对ICAM-1的黏附能力影响,并可能影响CD4+T细胞分泌细胞因子IL-4及IFN-γ的功能。 相似文献
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Jianguo Wu Hongyan Cui Zhifeng Zhu Li Wang Hong Li Desheng Wang 《Microbiology and immunology》2014,58(7):409-415
5.
Potassium channels are inhibited by several mono- and divalent cations. To identify sites involved in the interaction between
K+ channels and cationic effectors, we expressed the potato (Solanum tuberosum L.) guard-cell K+-uptake channel KST1 in Xenopus oocytes. This channel was reversibly blocked by extracellular Zn2+ in the micromolar range. In the presence of this heavy metal, steady-state currents were reduced in a pH-dependent but voltage-independent
manner. Since Zn2+-inhibition was less effective at elevated external proton concentrations, we generated alanine mutants with respect to both
extracellular histidines in KST1. Whereas substitution of the pore histidine H271 resulted in a reduced blockade by Zn2+, the channel mutant KST1-H160A in the S3-S4 linker lost most of its Zn2+ sensitivity. Since both histidines alter the susceptibility of KST1 to Zn2+, the block may predominantly result from these two sites. We thus conclude that the S3-S4 linker is involved in the formation
of the outer pore.
Received: 3 May 1999 / Accepted: 8 July 1999 相似文献
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Membrane fractions of pig cerebellum show Ca2+-ATPase activity and Ca2+ transport due to the presence of the secretory pathway Ca2+-ATPase (SPCA). The SPCA1 isoform shows a wide distribution in the neurons of pig cerebellum, where it is found in the Golgi complex of the soma of Purkinje, stellate, basket and granule cells, and also in more distal components of the secretory pathway associated with a synaptic localization such as in cerebellar glomeruli. The SPCA1 may be involved in loading the Golgi complex and the secretory vesicles of these specific neuronal cell types with Ca2+ and also Mn2+. This study of the cellular and subcellular localization of SPCA1 pumps relative to the sarco(endo) plasmic reticulum Ca2+-ATPase and plasma membrane Ca2+-ATPase pumps hints to a possible specific role of SPCA1 in controlling the luminal secretory pathway Ca2+ (or Mn2+) levels as well as the local cytosolic Ca2+ levels. In addition, it helps to specify the zones that are most vulnerable to Ca2+ and/or Mn2+ dyshomeostasis, a condition that is held responsible of an increasing number of neurological disorders. 相似文献
8.
Dukkipati A Vaclavikova J Waghray D Garcia KC 《Protein expression and purification》2006,50(2):203-214
CXCR4 belongs to the family of G protein-coupled receptors and mediates the various developmental and regulatory effects of the chemokine SDF-1alpha. In addition, CXCR4 acts as a co-receptor along with CD4 for the HIV-1 viral glycoprotein gp120. Recently, there has also been a small molecule described that antagonizes both SDF-1 and gp120 binding to CXCR4. The structural and mechanistic basis for this dual recognition ability of CXCR4 is unknown largely due to the technical challenges of biochemically producing the components of the various complexes. We expressed the human CXCR4 receptor using a modified baculovirus expression vector that facilitates a single step antibody affinity purification of CXCR4 to >80% purity from Hi5 cells. The recombinant receptor undergoes N-linked glycosylation, tyrosine sulfation and is recognized by the 12G5 conformation specific antibody against human CXCR4. We are able to purify CXCR4 alone as well as complexed with its endogenous ligand SDF-1, its viral ligand gp120, and a small molecule antagonist AMD3100 by ion-exchange chromatography. We anticipate that the expression and purification scheme described in this paper will facilitate structure-function studies aimed at elucidating the molecular basis for CXCR4 recognition of its endogenous chemokine and viral ligands. 相似文献
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Dimitrios Polychronopoulos Magdalena Foltman Arturo Calzada Karim Labib 《The EMBO journal》2009,28(19):2992-3004
The eukaryotic replisome is a crucial determinant of genome stability, but its structure is still poorly understood. We found previously that many regulatory proteins assemble around the MCM2‐7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2‐7 to other replisome components. Here, we show that the RPC associates with DNA polymerase α that primes each Okazaki fragment during lagging strand synthesis. Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2‐7 to DNA polymerase α. Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks. We show that cells lacking both Ctf4 and Mrc1 experience chronic activation of the DNA damage checkpoint during chromosome replication and do not complete the cell cycle. These findings indicate that coupling MCM2‐7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this process. 相似文献
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Anna Modrak-Wojcik Michal Gorka Katarzyna Niedzwiecka Konrad Zdanowski Joanna Zuberek Anna Niedzwiecka Ryszard Stolarski 《FEBS letters》2013
Initiation is the rate-limiting step during mRNA 5′ cap-dependent translation, and thus a target of a strict control in the eukaryotic cell. It is shown here by analytical ultracentrifugation and fluorescence spectroscopy that the affinity of the human translation inhibitor, eIF4E-binding protein (4E-BP1), to the translation initiation factor 4E is significantly higher when eIF4E is bound to the cap. The 4E-BP1 binding stabilizes the active eIF4E conformation and, on the other hand, can facilitate dissociation of eIF4E from the cap. These findings reveal the particular allosteric effects forming a thermodynamic cycle for the cooperative regulation of the translation initiation inhibition. 相似文献
13.
D. Gillis L.D. Shrode E. Krump C.M. Howard E.A. Rubie L.A. Tibbles J. Woodgett S. Grinstein 《The Journal of membrane biology》2001,181(3):205-214
The Na+/H+ exchanger (NHE) becomes activated by hyperosmolar stress, thereby contributing to cell volume regulation. The signaling pathway(s)
responsible for the shrinkage-induced activation of NHE, however, remain unknown. A family of mitogen-activated protein kinases
(MAPK), encompassing p42/p44 Erk, p38 MAPK and SAPK, has been implicated in a variety of cellular responses to changes in
osmolarity. We therefore investigated whether these kinases similarly signal the hyperosmotic activation of NHE. The time
course and osmolyte concentration dependence of hypertonic activation of NHE and of the three sub-families of MAPK were compared
in U937 cells. The temporal course and dependence on osmolarity of Erk and p38 MAPK activation were found to be similar to
that of NHE stimulation. However, while pretreatment of U937 cells with the kinase inhibitors PD98059 and SB203580 abrogated
the osmotic activation of Erk and p38 MAPK, respectively, it did not prevent the associated stimulation of NHE. Thus, Erk1/2
and/or p38 MAPK are unlikely to mediate the osmotic regulation of NHE. The kinetics of NHE activation by hyperosmolarity appeared
to precede SAPK activation. In addition, hyperosmotic activation of NHE persisted in mouse embryonic fibroblasts lacking SEK1/MKK4,
an upstream activator of SAPK. Moreover, shrinkage-induced activation of NHE still occurred in COS-7 cells that were transiently
transfected with a dominant-negative form of SEK1/MKK4 (SEK1/MKK4-A/L) that is expected to inhibit other isoforms of SEK as
well. Together, these results demonstrate that the stimulation of NHE and the activation of Erk, p38 MAPK and SAPK are parallel
but independent events.
Received: 27 November 2000/Revised: 20 March 2001 相似文献
14.
Sulfhydryl‐Based Inhibition of δ‐ALA‐D and Na+, K+‐ATPase Activities Depends on the Organoselenium Group Bonded to the Isoquinoline 下载免费PDF全文
Tuane Bazanella Sampaio Juliana Trevisan da Rocha Caroline Brandão Quines André Luiz Agnes Stein Gilson Zeni Cristina Wayne Nogueira 《Journal of cellular biochemistry》2017,118(5):1144-1150
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XiangYu Chen YingXin Shi YaPing Huang Min Ding Qiling Shen ChunJun Li JingNa Lin 《Journal of cellular and molecular medicine》2022,26(3):750
Islet β cell dedifferentiation is one of the most important mechanisms in the occurrence and development of diabetes. We studied the possible effects of chemokine stromal cell‐derived factor‐1 (SDF‐1) in the dedifferentiation of islet β cells. It was noted that the number of dedifferentiated islet β cells and the expression of SDF‐1 in pancreatic tissues significantly increased with diabetes. In islet β cell experiments, inhibition of SDF‐1 expression resulted in an increase in the number of dedifferentiated cells, while overexpression of SDF‐1 resulted in a decrease. This seemed to be contradicted by the effect of diabetes on the expression of SDF‐1 in pancreatic tissue, but it was concluded that this may be related to the loss of SDF‐1 activity. SDF‐1 binds to CXCR4 to form a complex, which activates and phosphorylates AKT, subsequently increases the expression of forkhead box O1 (FOXO1), and inhibits the dedifferentiation of islet β cells. This suggests that SDF‐1 may be a novel target in the treatment of diabetes. 相似文献
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Hyunsup Kim Hyemin Choi Jun-Sub Im Soon-Young Park Gwangsu Shin Jung-Ho Yoo Gyungmin Kim Joon-Kyu Lee 《The Journal of biological chemistry》2021,297(4)
The proper cellular response to DNA double-strand breaks (DSBs) is critical for maintaining the integrity of the genome. RecQL4, a DNA helicase of which mutations are associated with Rothmund–Thomson syndrome (RTS), is required for the DNA DSB response. However, the mechanism by which RecQL4 performs these essential roles in the DSB response remains unknown. Here, we show that RecQL4 and its helicase activity are required for maintaining the stability of the Mre11-Rad50-Nbs1 (MRN) complex on DSB sites during a DSB response. We found using immunocytochemistry and live-cell imaging that the MRN complex is prematurely disassembled from DSB sites in a manner dependent upon Skp2-mediated ubiquitination of Nbs1 in RecQL4-defective cells. This early disassembly of the MRN complex could be prevented by altering the ubiquitination site of Nbs1 or by expressing a deubiquitinase, Usp28, which sufficiently restored homologous recombination repair and ATM, a major checkpoint kinase against DNA DSBs, activation abilities in RTS, and RecQL4-depleted cells. These results suggest that the essential role of RecQL4 in the DSB response is to maintain the stability of the MRN complex on DSB sites and that defects in the DSB response in cells of patients with RTS can be recovered by controlling the stability of the MRN complex. 相似文献
18.
Hideo Taniura Naoya Tanabe Yumi Bando Natsumi Arai 《Development, growth & differentiation》2015,57(6):430-443
The Smc5–Smc6 complex contains a heterodimeric core of two SMC proteins and non‐Smc elements (Nse1–6), and plays an important role in DNA repair. We investigated the functional roles of Nse4 and Nse1 in Dictyostelium discoideum. Nse4 and Nse3 expressed as Flag‐tagged fusion proteins were highly enriched in nuclei, while Nse1 was localized in whole cells. Using yeast two‐hybrid assays, only the interaction between Nse3 and Nse1 was detected among the combinations. However, all of the interactions among these three proteins were recognized by co‐immunoprecipitation assay using cell lysates prepared from the cells expressing green fluorescent protein (GFP)‐ or Flag‐tagged fusion proteins. GFP‐tagged Nse1, which localized in whole cells, was translocated to nuclei when co‐expressed with Flag‐tagged Nse3 or Nse4. RNAi‐mediated Nse1 and Nse4 knockdown cells (Nse1 KD and Nse4 KD cells) were generated and found to be more sensitive to UV‐induced cell death than control cells. Upon starvation, Nse1 and Nse4 KD cells had increases in the number of smaller fruiting bodies that formed on non‐nutrient agar plates or aggregates that formed under submerged culture. We found a reduction in the mRNA level of pdsA, in vegetative and 8 h‐starved Nse4 KD cells, and pdsA knockdown cells displayed effects similar to Nse4 KD cells. Our results suggest that Nse4 and Nse1 are involved in not only the cellular DNA damage response but also cellular development in D. discoideum. 相似文献
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Moreno Marchiafava Paolo Boldrini Giuseppe Battaglia Sergio Scaccianoce Francesco Matrisciano Anna Pittaluga Ferdinando Nicoletti 《Journal of neurochemistry》2013,125(5):649-656
The α2δ subunit of voltage‐sensitive calcium channels (VSCCs) is the molecular target of pregabalin and gabapentin, two drugs marked for the treatment of focal epilepsy, neuropathic pain, and anxiety disorders. Expression of the α2δ subunit is up‐regulated in the dorsal horns of the spinal cord in models of neuropathic pain, suggesting that plastic changes in the α2δ subunit are associated with pathological states. Here, we examined the expression of the α2δ‐1 subunit in the amygdala, hippocampus, and frontal cortex in the trimethyltiazoline (TMT) mouse model of innate anxiety. TMT is a volatile molecule present in the feces of the rodent predator, red fox. Mice that show a high defensive behavior during TMT exposure developed anxiety‐like behavior in the following 72 h, as shown by the light–dark test. Anxiety was associated with an increased expression of the α2δ‐1 subunit of VSCCs in the amygdaloid complex at all times following TMT exposure (4, 24, and 72 h). No changes in the α2δ‐1 protein levels were seen in the hippocampus and frontal cortex of mice exposed to TMT. Pregabalin (30 mg/kg, i.p.) reduced anxiety‐like behavior in TMT‐exposed mice, but not in control mice. These data offer the first demonstration that the α2δ‐1 subunit of VSCCs undergoes plastic changes in a model of innate anxiety, and supports the use of pregabalin as a disease‐dependent drug in the treatment of anxiety disorders. 相似文献