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991.
Expression of an Insect Excitatory Toxin, BmK IT, from the Scorpion, Buthus martensii Karsch, and its Biological Activity 总被引:2,自引:0,他引:2
An insect excitatory toxin from Buthus martensii Karsch (BmK IT) was cloned into the expression vector, pTWIN1, and expressed into Escherichia coli BL21 (DE3) host cells. The soluble fusion expression of CBD-intein-BmK IT was obtained. The recombinant BmK IT was purified by two anion-exchange chromatography columns and one gel chromatography column. Bioassays were carried out to verify the toxicity of this recombinant toxin. At the end of a 96 h experimental period, 83% of cotton bollworm larvae were killed with an LT(50) value of 58-62 h. Furthermore, the average weight of larvae fed on BmK IT-containing media was approx 4% of that of the control groups. The results indicate that the expressed and purified recombinant BmK IT has biological activity. 相似文献
992.
Pogozheva ID Chai BX Lomize AL Fong TM Weinberg DH Nargund RP Mulholland MW Gantz I Mosberg HI 《Biochemistry》2005,44(34):11329-11341
Specific interactions of human melanocortin-4 receptor (hMC4R) with its nonpeptide and peptide agonists were studied using alanine-scanning mutagenesis. The binding affinities and potencies of two synthetic, small-molecule agonists (THIQ, MB243) were strongly affected by substitutions in transmembrane alpha-helices (TM) 2, 3, 6, and 7 (residues Glu(100), Asp(122), Asp(126), Phe(261), His(264), Leu(265), and Leu(288)). In addition, a I129A mutation primarily affected the binding and potency of THIQ, while F262A, W258A, Y268A mutations impaired interactions with MB243. By contrast, binding affinity and potency of the linear peptide agonist NDP-MSH were substantially reduced only in D126A and H264A mutants. Three-dimensional models of receptor-ligand complexes with their agonists were generated by distance-geometry using the experimental, homology-based, and other structural constraints, including interhelical H-bonds and two disulfide bridges (Cys(40)-Cys(279), Cys(271)-Cys(277)) of hMC4R. In the models, all pharmacophore elements of small-molecule agonists are spatially overlapped with the corresponding key residues (His(6), d-Phe(7), Arg(8), and Trp(9)) of the linear peptide: their charged amine groups interact with acidic residues from TM2 and TM3, similar to His(6) and Arg(6) of NDP-MSH; their substituted piperidines mimic Trp(9) of the peptide and interact with TM5 and TM6, while the d-Phe aromatic rings of all three agonists contact with Leu(133), Trp(258), and Phe(261) residues. 相似文献
993.
Distinct domains of Bcl-XL are involved in Bax and Bad antagonism and in apoptosis inhibition 总被引:3,自引:0,他引:3
Pro-survival factor Bcl-X(L) can antagonize the pro-apoptotic functions of Bax and Bad via two distinct mechanisms. It can block Bax-mediated cell death by preventing Bax translocation from the cytosol to mitochondria. On the other hand, Bcl-X(L) can neutralize Bad by sequestering it to mitochondria. In order to map the domains of Bcl-X(L) involved in inhibiting Bax and Bad, we have carried out mutational analyses of this protein. This was done by deleting the key domains of Bcl-X(L), including its BH1-4 domains, the flexible loop, the C-terminal hydrophobic domain, and segments of the alpha5-alpha6 hairpin. The resulting Bcl-X(L) mutant constructs were then co-transfected with either GFP-Bax or GFP-Bad. We found that the BH1-4 domains and the C-terminal segment of Bcl-X(L) were essential for blocking Bax localization to mitochondria. On the other hand, only its BH1 and BH3 domains and the C-terminal hydrophobic segment were necessary for sequestering Bad to mitochondria. In addition, by immunoprecipitation analyses, we found that these deletions differentially affected the ability of the Bcl-X(L) mutant proteins to bind Bax and Bad. Finally, cell viability assays indicated that the BH1-4 domains of Bcl-X(L) were the primary domains required for inhibiting staurosporine-induced apoptosis, suggesting that distinct domains of Bcl-X(L) are involved in antagonizing Bax and Bad and in apoptosis inhibition. 相似文献
994.
995.
Ong E Gao XP Predescu D Broman M Malik AB 《American journal of physiology. Lung cellular and molecular physiology》2005,289(6):L1094-L1103
We addressed the in vivo role of phosphatidylinositol 3-kinase-gamma (PI3K-gamma) in signaling the sequestration of polymorphonuclear leukocytes (PMNs) in lungs and in the mechanism of inflammatory lung vascular injury. We studied mice with deletion of the p110 catalytic subunit of PI3K-gamma (PI3K-gamma(-/-) mice). We measured lung tissue PMN sequestration, microvascular permeability, and edema formation after bacteremia induced by intraperitoneal Escherichia coli challenge. PMN infiltration into the lung interstitium in PI3K-gamma(-/-) mice as assessed morphometrically was increased 100% over that in control mice within 1 h after bacterial challenge. PI3K-gamma(-/-) mice also developed a greater increase in lung microvascular permeability after E. coli challenge, resulting in edema formation. The augmented lung tissue PMN sequestration in PI3K-gamma(-/-) mice was associated with increased expression of the PMN adhesive proteins CD47 and beta(3)-integrins. We observed increased association of CD47 and beta(3)-integrins with the extracellular matrix protein vitronectin in lungs of PI3K-gamma(-/-) mice after E. coli challenge. PMNs from these mice also showed increased beta(3)-integrin expression and augmented beta(3)-integrin-dependent PMN adhesion to vitronectin. These results point to a key role of PMN PI3K-gamma in negatively regulating CD47 and beta(3)-integrin expression in gram-negative sepsis. PI3K-gamma activation in PMNs induced by E. coli may modulate the extent of lung tissue PMN sequestration secondary to CD47 and beta(3)-integrin expression. Therefore, the level of PI3K-gamma activation may be an important determinant of PMN-dependent lung vascular injury. 相似文献
996.
997.
Kermorvant-Duchemin E Sennlaub F Sirinyan M Brault S Andelfinger G Kooli A Germain S Ong H d'Orleans-Juste P Gobeil F Zhu T Boisvert C Hardy P Jain K Falck JR Balazy M Chemtob S 《Nature medicine》2005,11(12):1339-1345
Nitrative stress has an important role in microvascular degeneration leading to ischemia in conditions such as diabetic retinopathy and retinopathy of prematurity. Thus far, mediators of nitrative stress have been poorly characterized. We recently described that trans-arachidonic acids are major products of NO(2)(*)-mediated isomerization of arachidonic acid within the cell membrane, but their biological relevance is unknown. Here we show that trans-arachidonic acids are generated in a model of retinal microangiopathy in vivo in a NO(*)-dependent manner. They induce a selective time- and concentration-dependent apoptosis of microvascular endothelial cells in vitro, and result in retinal microvascular degeneration ex vivo and in vivo. These effects are mediated by an upregulation of the antiangiogenic factor thrombospondin-1, independently of classical arachidonic acid metabolism. Our findings provide new insight into the molecular mechanisms of nitrative stress in microvascular injury and suggest new therapeutic avenues in the management of disorders involving nitrative stress, such as ischemic retinopathies and encephalopathies. 相似文献
998.
Xie ZF Chai KY Piao HR Kwak KC Quan ZS 《Bioorganic & medicinal chemistry letters》2005,15(21):4803-4805
A series of 7-alkoxyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline derivatives was synthesized using 6-hydroxy-3,4-dihydro-1H-quinolin-2-one as a starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and the subcutaneous (s.c.) pentylenetetrazol test (scMet test), and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). MES and scMet tests show that 7-(4-fluorobenzyloxy)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline 4l was found to be the most potent with ED50 value of 11.8 and 6.7 mg kg(-1) and protective index (PI = TD50/ED50) value of 4.6 and 8.1, respectively. 相似文献
999.
Park JH Han ET Kim WH Shin EH Guk SM Kim JL Chai JY 《The Korean journal of parasitology》2005,43(4):129-134
To determine the status of Enterobius vermicularis infection among children living on western and southern coastal islands of the Republic of Korea, children (3-10 years) in 39 kindergartens and primary schools were examined using the cello-tape anal swab method, during July and August 2000. Of 1,661 children examined, 307 (18.5%) were found to be positive for E. vermicularis eggs. The highest infection rate (59.3%) was found in a kindergarten and a branch school of Shinyang primary school on Chujado, Jeju-do (Province). Remarkable differences in egg positive rates were observed in different localities. The egg positive rate for boys (21.3%) was significantly higher than that of girls (15.4%) (P = 0.02). However, positive rates were not significantly dependent on age. The results of the present study show that E. vermicularis infection is highly prevalent among pre-school and primary school children living on the western and southern coastal islands of the Republic of Korea, and indicate the need for efforts to control this infection. 相似文献
1000.
The present study was performed to investigate the infection status with helminth in a group of feral cats in Korea. More than 29 helminth species including adults or eggs were detected in visceral and fecal samples of the examined cats. Among these were a host of nematodes, including toxocarids, Ancylostoma sp. and the larva of Anisakis simplex; trematodes, including Clonorchis sinensis, Paragonimus westermani, Eurytrema pancreaticum, Pharyngostomum cordatum, Metagonimus spp., Heterophyes nocens, Pygidiopsis summa, Heterophyopsis continua, Stictodora fuscata, Stictodora lari, Acanthotrema felis, Stellantchasmus falcatus, Centrocestus armatus, Procerovum varium, Cryptocotyle sp., Echinostoma revolutum, Echinostoma hortense, Echinochasmus japonicus, Stephanoprora sp., Plagiorchis muris, Neodiplostomum sp. and diplostomulum. We also detected a variety of cestodes, including Spirometra erinacei, Taenia taeniaeformis and unidentified species of tapeworm. We also found examples of the acanthocephalan, Bolbosoma sp. In our assessment of the stools, we detected at least 12 species of helminth eggs. These findings confirmed that feral cats in Korea are infected with a variety of helminth parasite species. Furthermore, among the helminths detected, E. pancreaticum, S. fuscata, S. lari, A. felis, S. falcatus, C. armatus, P. varium, Cryptocotyle sp., E. revolutum, E. japonicus, Stephanoprora sp., P. muris, Neodiplostomum sp. and Bolbosoma sp. represent helminth fauna which have not been reported previously in feral cats in the Republic of Korea. 相似文献