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981.
Apostolov EO Basnakian AG Yin X Ok E Shah SV 《American journal of physiology. Heart and circulatory physiology》2007,292(4):H1836-H1846
The ability of modified low-density lipoptoteins (LDLs) to induce both proliferation and death of endothelial cells is considered to be a mechanism of early atherosclerosis development. We previously showed that carbamylated LDL (cLDL) induces human coronary artery endothelial cell (HCAEC) death in vitro. This effect is similar to the atherogenic action of oxidized LDL (oxLDL) that induces the proliferation and death of endothelial cells. The present study was designed to analyze a potential proliferative effect of cLDL and whether proliferation caused by modified LDLs is related to cell death. Cultured HCAECs were exposed to different concentrations of modified LDL or native LDL for varying periods of time. Cell proliferation measured by bromodeoxyuridine incorporation and S-phase analysis was dose-dependently increased in the presence of cLDL (6.25-200 microg/ml). The proliferation induced by cLDL or oxLDL was associated with cell death and increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK). Inhibition of cLDL- or oxLDL-induced proliferation by aphidicolin (1 microg/ml) was protective against both short-term cell death measured by lactate dehydrogenase release into the medium and long-term cell viability visualized by cell multiplication. Inhibition of ERK phosphorylation led to a significant decrease of DNA synthesis and cell rescue from injury by modified LDLs, while inhibition of JNK phosphorylation had an only partial rescue effect without involvement in cell proliferation. These data are the first evidence that endothelial cell death induced by cLDL or oxLDL is mediated by cell proliferation through the mitogen-activated protein kinase pathway. 相似文献
982.
Innovative proteomic approaches for cancer biomarker discovery 总被引:1,自引:0,他引:1
Substantial technological advances in proteomics and related computational science have been made in the past few years. These advances overcome in part the complexity and heterogeneity of the human proteome, permitting quantitative analysis and identification of protein changes associated with tumor development. Here, we discuss some of these advances that are uncovering new cancer biomarkers that have potential to detect cancer at early and curable stages and address remaining challenges. 相似文献
983.
van Swieten PF Samuel E Hernández RO van den Nieuwendijk AM Leeuwenburgh MA van der Marel GA Kessler BM Overkleeft HS Kisselev AF 《Bioorganic & medicinal chemistry letters》2007,17(12):3402-3405
The ubiquitin-proteasome pathway degrades the majority of proteins in mammalian cells and plays an essential role in the generation of antigenic peptides presented by major histocompatibility class I molecules. Proteasome inhibitors are of great interest as research tools and drug candidates. Most work on proteasome inhibitors has focused on the inhibition of the chymotryptic-like (beta5) sites; little attention has been paid to the inhibition of two other types of active sites, the trypsin-like (beta2) and the caspase-like (beta1). We report here the development of the first cell-permeable and highly selective inhibitors (4 and 5) of the proteasome's caspase-like site. The selectivity of the compounds is directly and unambiguously established by Staudinger-Bertozzi labeling of proteasome subunits covalently modified with azide-functionalized inhibitor 5. This labeling reveals that the caspase-like site of the immunoproteasome (beta1i) is a preferred target of this compound. These compounds can be used as tools to study roles of beta1 and beta1i sites in generation of specific antigenic peptides and their potential role as co-targets of anti-cancer drugs. 相似文献
984.
Synthesis and structure-activity relationship of 4-(2-aryl-cyclopropylamino)-quinoline-3-carbonitriles as EGFR tyrosine kinase inhibitors 总被引:1,自引:0,他引:1
Pannala M Kher S Wilson N Gaudette J Sircar I Zhang SH Bakhirev A Yang G Yuen P Gorcsan F Sakurai N Barbosa M Cheng JF 《Bioorganic & medicinal chemistry letters》2007,17(21):5978-5982
Synthesis and structure-activity relationship of a series of 4-(2-aryl-cyclopropylamino)-quinoline-3-carbonitrile derivatives as EGFR inhibitors is described. Compounds 29 and 30 showed potent in vitro inhibitory activity in the enzymatic assay as well as in the functional cellular assay. They are moderately selective against other types of tyrosine kinases. 相似文献
985.
986.
Crystal structures of TM0549 and NE1324--two orthologs of E. coli AHAS isozyme III small regulatory subunit
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Petkowski JJ Chruszcz M Zimmerman MD Zheng H Skarina T Onopriyenko O Cymborowski MT Koclega KD Savchenko A Edwards A Minor W 《Protein science : a publication of the Protein Society》2007,16(7):1360-1367
Crystal structures of two orthologs of the regulatory subunit of acetohydroxyacid synthase III (AHAS, EC 2.2.1.6) from Thermotoga maritima (TM0549) and Nitrosomonas europea (NE1324) were determined by single-wavelength anomalous diffraction methods with the use of selenomethionine derivatives at 2.3 A and 2.5 A, respectively. TM0549 and NE1324 share the same fold, and in both proteins the polypeptide chain contains two separate domains of a similar size. Each protein contains a C-terminal domain with ferredoxin-type fold and an N-terminal ACT domain, of which the latter is characteristic for several proteins involved in amino acid metabolism. The ferredoxin domain is stabilized by a calcium ion in the crystal structure of NE1324 and by a Mg(H2O)(6)2+ ion in TM0549. Both TM0549 and NE1324 form dimeric assemblies in the crystal lattice. 相似文献
987.
Alaimella cincta Cobb 1920 and Alaimella macramphis sp. n. are described and illustrated. Both the species were first recorded for the White Sea in northern Russia. A. cincta occurs in the shells of the agglutinated foraminiferan Reophax curtus, as well as freely in bottom sediments. A. macramphis sp. n. is described from a single male sampled from bottom sediments. A. macramphis sp. n. is distinguished from two previously known species of Alaimella (A. cincta Cobb 1920 and A. truncate Cobb 1920) by having a longer body, longer cephalic setae, and a wide amphid equal to the respective body diameter. The new species also differs from A. truncate by the distinct striation of the cuticular annulations. The Alaimella species are additionally characterized by having a posterior glandular widening of the esophagus. An emended diagnosis of the genus Alaimella Cobb 1920 and a key for species identification are provided. 相似文献
988.
Interference competition by Argentine ants displaces native ants: implications for biotic resistance to invasion 总被引:1,自引:0,他引:1
The Argentine ant Linepithema humile (Dolichoderinae) is one of the most widespread invasive ant species in the world. Throughout its introduced range, it is
associated with the loss or reduced abundance of native ant species. The mechanisms by which these native species are displaced
have received limited attention, particularly in Australia. The role of interference competition in the displacement of native
ant species by L. humile was examined in coastal vegetation in central Victoria (southeastern Australia). Foragers from laboratory colonies placed
in the field consistently and rapidly displaced the tyrant ant Iridomyrmex bicknelli, the big-headed ant Pheidole sp. 2, and the pony ant Rhytidoponera victoriae from baits. Numerical and behavioural dominance enabled Argentine ants to displace these ants in just 20 min; the abundance
of native species at baits declined 3.5–24 fold in direct relation to the rapid increase in L. humile. Most precipitous was the decline of I. bicknelli, even though species in this typically dominant genus have been hypothesized to limit invasion of L. humile in Australia. Interspecific aggression contributed strongly to the competitive success of Argentine ants at baits. Fighting
occurred in 50–75% of all observed interactions between Argentine and native ants. This study indicates that Argentine ants
recruit rapidly, numerically dominate, and aggressively displace from baits a range of Australian native ant species from
different subfamilies and functional groups. Such direct displacement is likely to reduce native biodiversity and indirectly
alter food web structure and ecosystem processes within invaded areas. Biotic resistance to Argentine ant invasion from native
ants in this coastal community in southeastern Australia is not supported in this study. 相似文献
989.
Banfalvi G Ujvarosi K Trencsenyi G Somogyi C Nagy G Basnakian A 《Apoptosis : an international journal on programmed cell death》2007,12(7):1219-1228
Murine pre-B-cells grown in the presence of lower (1 μM) or higher (5 μM) concentration of cadmium chloride were separated
into 13 fractions by centrifugal elutriation. The rate of DNA synthesis after cadmium treatment determined in permeable cells
was dependent on cell culture density during cadmium treatment. Cell cycle analysis revealed a shift in the profile of DNA
synthesis from replicative to repair DNA synthesis upon cadmium treatment. The study of the relationship between cell culture
density and cell diameter at lower and higher cell densities in the presence of 1 μM cadmium chloride concentration showed
that a. at 5×105 cell/ml or lower densities cells were shrinking indicating apoptotic changes, b. at higher cell culture densities the average
cell size increased, c. the treatment of cells with low CdCl2 concentration (1 μM) at higher cell culture density (>5×105 cell/ml) did not change significantly the average cell diameter. At 5 μM cadmium concentration and higher cell culture densities
(>5×105 cell/ml) the average cell size decreased in each elutriated fraction. Most significant inhibition of cell growth took place
in early S phase (2.0–2.5 C value). Apoptotic chromatin changes in chromatin structure after cadmium treatment were seen as
large extensive disruptions, holes in the nuclear membrane and stickiness of incompletely folded chromosomes. 相似文献
990.