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141.
Christopher J Frederickson Sang W Suh Jae-Young Koh Yoo K Cha Richard B Thompson Christopher J LaBuda Rengarajan V Balaji Math P Cuajungco 《The journal of histochemistry and cytochemistry》2002,50(12):1659-1662
The membrane-impermeable chelator CaEDTA was introduced extracellularly among neurons in vivo and in vitro for the purpose of chelating extracellular Zn(2+). Unexpectedly, this treatment caused histochemically reactive Zn(2+) in intracellular compartments to drop rapidly. The same general result was seen with intravesicular Zn(2+), which fell after CaEDTA infusion into the lateral ventricle of the brain, with perikaryal Zn(2+) in Purkinje neurons (in vivo) and with cortical neurons (in vitro). These findings suggest either that the volume of zinc ion efflux and reuptake is higher than previously suspected or that EDTA can enter cells and vesicles. Caution is therefore warranted in attempting to manipulate extracellular or intracellular Zn(2+) selectively. 相似文献
142.
Hye Mi Kim Boonjae Jang Young Eun Cheon Myunghyun Paik Suh Junghun Suh 《Journal of biological inorganic chemistry》2009,14(1):151-157
Catalytic drugs based on target-selective artificial proteases have been proposed as a new paradigm in drug design. Peptide-cleavage
agents selective for pathogenic proteins of Alzheimer’s disease, type 2 diabetes mellitus or Parkinson’s disease have been
prepared using the Co(III) aqua complex (Co(III)cyclen) of 1,4,7,10-tetraazacyclododecane as the catalytic center. In the
present study, the Co(III) aqua complex (Co(III)oxacyclen) of 1-oxa-4,7,10-triazacyclododecane was examined in search of an
improved catalytic center for peptide-cleavage agents. An X-ray crystallographic study of [Co(oxacyclen)(CO3)](ClO4), titration of Co(III)oxacyclen, and kinetic studies on the cleavage of albumin, γ-globulin, lysozyme, and myoglobin by Co(III)oxacyclen
were carried out. Considerably higher proteolytic activity was observed for Co(III)oxacyclen in comparison with Co(III)cyclen,
indicating that better target-selective artificial metalloproteases would be obtained using Co(III)oxacyclen as the catalytic
center. The improved proteolytic activity was attributed to either steric effects or the increased Lewis acidity of the Co(III)
center. The kinetic data also predicted that side effects due to the cleavage of nontarget proteins by a catalytic drug based
on Co(III)oxacyclen would be insignificant. 相似文献
143.
P2Y12 antagonist attenuates eosinophilic inflammation and airway hyperresponsiveness in a mouse model of asthma 下载免费PDF全文
Dong‐Hyeon Suh Hoang Kim Tu Trinh Jing‐Nan Liu Le Duy Pham Sang Myun Park Hae‐Sim Park Yoo Seob Shin 《Journal of cellular and molecular medicine》2016,20(2):333-341
Leukotriene E4 (LTE4) that plays a key role in airway inflammation is expressed on platelets and eosinophils. We investigated whether blocking of the P2Y12 receptor can suppress eosinophilic inflammation in a mouse model of asthma because platelets and eosinophils share this receptor to be activated. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by OVA nebulization. On each challenge day, clopidogrel, a P2Y12 antagonist was administered 30 min. before each challenge. Forty‐eight hours after the last OVA challenge, mice were assessed for airway hyperresponsiveness (AHR), cell composition and cytokine levels, including chemokine ligand 5 (CCL5), in bronchoalveolar lavage (BAL) fluid. EOL cells were treated with LTE4, with or without clopidogrel treatment, and intracellular and extracellular eosinophil cationic protein (ECP) expressions were measured to find the inhibiting function of P2Y12 antagonist on eosinophilic activation. The levels of P2Y12 expression were increased markedly in the lung homogenates of OVA‐sensitized and ‐challenged mice after platelet depletion. Administration of clopidogrel decreased AHR and the number of airway inflammatory cells, including eosinophils, in BAL fluid following OVA challenge. These results were associated with decreased levels of Th2 cytokines and CCL5. Histological examination showed that inflammatory cells as well as mucus‐containing goblet cells were reduced in clopidogrel‐administered mice compared to vehicle‐treated mice. Clopidogrel inhibited extracellular ECP secretion after LTE4 stimulation in EOL‐1 cells. Clopidogrel could prevent development of AHR and airway inflammation in a mouse model of asthma. P2Y12 can be a novel therapeutic target to the suppression of eosinophils in asthma. 相似文献
144.
Hwang IK Lee CH Li H Yoo KY Choi JH Kim DW Kim DW Suh HW Won MH 《Neurochemical research》2008,33(7):1309-1315
Similarities between age-related changes in the canine and human brain have resulted in the general acceptance of the canine brain as a model of human brain aging. The hippocampus is essentially required for intact cognitive ability and appears to be particularly vulnerable to the aging process. We observed changes in ionized calcium-binding adapter molecule 1 (Iba-1, a microglial marker) immunoreactivity and protein levels in the hippocampal dentate gyrus and CA1 region of adult (2-3 years) and aged (10-12 years) dogs. We also observed the interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, protein levels in these groups. In the dentate gyrus and CA1 region of the adult dog, Iba-1 immunoreactive microglia were well distributed and their processes were highly ramified. However, in the aged dog, the processes of Iba-1 immunoreactive microglia were hypertrophied in the dentate gyrus. Moreover, Iba-1 protein level in the dentate gyrus in the aged dog was higher than in the adult dog. IFN-gamma expression was increased in the dentate gyrus homogenates of aged dogs than adult dogs. In addition, we found that some neurons were positive to Fluoro-Jade B (a marker for neuronal degeneration) in the dentate polymorphic layer, but not in the hippocampal CA1 region in the aged dog. These results suggest that Iba-1 immunoreactive microglia are hypertrophied in the dentate gyrus in the aged dog. 相似文献
145.
Crystal structure of deoxycytidylate hydroxymethylase from bacteriophage T4, a component of the deoxyribonucleoside triphosphate-synthesizing complex 下载免费PDF全文
Bacteriophage T4 deoxycytidylate hydroxymethylase (EC 2.1.2.8), a homodimer of 246-residue subunits, catalyzes hydroxymethylation of the cytosine base in deoxycytidylate (dCMP) to produce 5-hydroxymethyl-dCMP. It forms part of a phage DNA protection system and appears to function in vivo as a component of a multienzyme complex called deoxyribonucleoside triphosphate (dNTP) synthetase. We have determined its crystal structure in the presence of the substrate dCMP at 1.6 A resolution. The structure reveals a subunit fold and a dimerization pattern in common with thymidylate synthases, despite low (approximately 20%) sequence identity. Among the residues that form the dCMP binding site, those interacting with the sugar and phosphate are arranged in a configuration similar to the deoxyuridylate binding site of thymidylate synthases. However, the residues interacting directly or indirectly with the cytosine base show a more divergent structure and the presumed folate cofactor binding site is more open. Our structure reveals a water molecule properly positioned near C-6 of cytosine to add to the C-7 methylene intermediate during the last step of hydroxymethylation. On the basis of sequence comparison and crystal packing analysis, a hypothetical model for the interaction between T4 deoxycytidylate hydroxymethylase and T4 thymidylate synthase in the dNTP-synthesizing complex has been built. 相似文献
146.
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148.
6,7-Dichloroquinoline-5,8-dione (1) was reacted with a number of 2-aminopyridine derivatives. Of the several possible products of this reaction, 4a,10,11-triazabenzo[3,2-a]fluorene-5,6-dione (6), produced by condensation and rearrangement, was obtained as the major product, and its structure was subsequently unambigously determined by X-ray crystallographic study. Ortho-quinones were produced via nucleophilic substitution at position C7, which was unexpected, considering that para-quinones were produced via C6 substitution in the reaction between compound 1 and ethyl acetoacetate in our previous work. Such unexpected nucleophilic substitution at C7 provides an effective, yet simple route, to the preparation of biologically active ortho-quinone derivatives. 相似文献
149.
Translocation of beta-catenin into the nucleus independent of interactions with FG-rich nucleoporins
beta-Catenin nuclear import has been found to be independent of classical nuclear localization signal (NLS) nuclear import factors. Here, we test the hypothesis that beta-catenin interacts directly with nuclear pore proteins to mediate its own transport. We show that beta-catenin, unlike importin-beta, does not interact detectably with Phe/Gly(FG)-repeat-rich nuclear pore proteins or nucleoporins (Nups). Moreover, unlike NLS-containing proteins, beta-catenin nuclear import is not inhibited by wheat germ agglutinin (WGA) or excess importin-beta. These results suggest beta-catenin nuclear translocation does not involve direct interactions with FG-Nups. However, beta-catenin has two regions that can target it to the nucleus, and its import is cold sensitive, indicating that beta-catenin nuclear import is still an active process. Transport is blocked by a soluble form of the C-cadherin cytoplasmic domain, suggesting that masking of the nuclear targeting signal may be a mechanism of regulating beta-catenin subcellular localization. 相似文献
150.
Suh YG Kim YH Park MH Choi YH Lee HK Moon JY Min KH Shin DY Jung JK Park OH Jeon RO Park HS Kang SA 《Bioorganic & medicinal chemistry letters》2001,11(4):559-562
The structure-activity relationship and molecular modelings of a novel pimarane COX-2 inhibitor are reported. Particularly, a series of linker extended analogues designed on the basis of these studies exhibited significantly enhanced COX-2 inhibitory activities and selectivities. 相似文献