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991.
DHA induces ER stress and growth arrest in human colon cancer cells: associations with cholesterol and calcium homeostasis 总被引:2,自引:0,他引:2
Jakobsen CH Størvold GL Bremseth H Follestad T Sand K Mack M Olsen KS Lundemo AG Iversen JG Krokan HE Schønberg SA 《Journal of lipid research》2008,49(10):2089-2100
Polyunsaturated fatty acids (PUFAs) are normal constituents of the diet, but have properties different from other fatty acids (e.g., through generation of signaling molecules). N-3 PUFAs reduce cancer cell growth, but no unified mechanism has been identified. We show that docosahexaenoic acid (DHA; 22:6 n-3) causes extensive changes in gene expression patterns at mRNA level in the colon cancer cell line SW620. Early changes include unfolded protein response (UPR) and increased levels of phosphorylated eIF2alpha as verified at protein level. The latter is considered a hallmark of endoplasmic reticulum (ER) stress and is abundantly present already after 3 h. It may coordinate many of the downstream changes observed, including signaling pathways for cell cycle arrest/apoptosis, calcium homeostasis, cholesterol metabolism, ubiquitination, and proteasomal degradation. Also, eicosapentaenoic acid (EPA), but not oleic acid (OA), induced key mediators of ER stress and UPR at protein level. Accumulation of esterified cholesterol was not compensated for by increased total levels of cholesterol, and mRNAs for cholesterol biosynthesis as well as de novo synthesis of cholesterol were reduced. These results suggest that cytotoxic effects of DHA are associated with signaling pathways involving lipid metabolism and ER stress. 相似文献
992.
Thedieck C Kalbacher H Kratzer U Lammers R Stevanovic S Klein G 《Journal of molecular biology》2008,378(1):145-153
The Ca2 +-dependent membrane-spanning classical cadherins bind directly to cytosolic catenins. This cadherin-catenin interaction is known to be critical for the fundamental role of cadherins in cell-cell adhesion. The small subfamily of the 7D-cadherins, however, cannot interact with catenins due to their highly truncated cytoplasmic tail. Thus far, no cytoplasmic interaction partner for the 7D-cadherins has been described. With the use of the cytoplasmic domain of the Ksp (kidney-specific)-cadherin, which belongs to the family of 7D-cadherins, as bait in affinity chromatography with human kidney lysates, the small heat-shock protein αB-crystallin was identified by matrix-assisted laser desorption/ionization-time-of-flight analysis as a cytosolic binding partner of Ksp-cadherin. This interaction was verified by co-immunoprecipitation analysis. With the use of overlapping peptides representing the entire αB-crystallin molecule, the N-terminal part of αB-crystallin, which does not possess chaperone activity, was identified as responsible for the binding to Ksp-cadherin. This interaction was found to be specific since only the cytoplasmic domain of Ksp-cadherin, but not LI (liver-intestine)-cadherin (another member of the 7D-cadherin family), interacted with αB-crystallin. In the human kidney, both αB-crystallin and Ksp-cadherin co-localize to cells of the collecting duct. They also co-localize with the actin cytoskeleton and co-precipitate with the latter. These findings suggest that the interaction of Ksp-cadherin with αB-crystallin is important for the connection of Ksp-cadherin to the cytoskeleton and thus for maintaining tissue integrity in the kidney. 相似文献
993.
We have analyzed the intracellular transport of the spike (S) protein of infectious bronchitis virus (IBV), an avian coronavirus. Surface expression was analyzed by immunofluorescence microscopy, by surface biotinylation, and by syncytium formation by S-expressing cells. By applying these methods, the S protein was found to be retained intracellularly. Tyr1143 in the cytoplasmic tail was shown to be a crucial component of the retention signal. Deletion of a dilysine motif that has previously been suggested to function as a retrieval signal did not abolish intracellular retention. Treatment of the S proteins with endoglycosidases did not reveal any differences between the parental and the mutant proteins. Furthermore, all S proteins analyzed were posttranslationally cleaved into the subunits S1 and S2. In coexpression experiments, the S protein was found to colocalize with a Golgi marker. Taken together, these results indicate that the S protein of IBV is retained at a late Golgi compartment. Therefore, this viral surface protein differs from the S proteins of transmissible gastroenteritis virus and severe acute respiratory syndrome coronavirus, which are retained at a pre-Golgi compartment or transported to the cell surface, respectively. The implications of these differences are discussed. 相似文献
994.
Wilhelm M Wittsiepe J Lemm F Ranft U Krämer U Fürst P Röseler SC Greshake M Imöhl M Eberwein G Rauchfuss K Kraft M Winneke G 《Mutation research》2008,659(1-2):83-92
Prenatal exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) can affect neurobehavioral development of infants and children. This effect may be mediated through disruption of thyroid hormone homeostasis. However, epidemiological studies reveal no consistent influence of PCDD/Fs and PCBs on thyroid status and neurodevelopment at environmental background levels. The effects may resolve with time of further decreasing exposure to these compounds. The aim of this study was to find out if there are still effects related to prenatal PCDD/F and PCB observable at the meanwhile decreased levels of exposure by using the same methods which have been applied in similar studies during the last 10 years in Europe. The birth cohort study was initiated in the year 2000 in the industrialized city of Duisburg, Germany. 232 healthy mother-infant pairs were recruited between 2000 and 2002. Dioxins, dioxin-like PCBs and six indicator PCBs were analyzed in maternal blood during pregnancy and in maternal milk following extraction and sample clean-up by HRGC/HRMS. Thyroid stimulating hormone (TSH), total thyroxine (T4), total triiodothyronine (T3), free thyroxine (FT4) and free triiodothyronine (FT3) were measured in serum samples of the pregnant women and in cord serum samples by chemiluminescent immunometric assay. Neurological examinations were performed at ages 2 weeks and 18 months using the neurological optimality score (NOS), mental and motor development were assessed using the Bayley Scales of Infant Development (BSID) at ages 12 and 24 months. Multiple linear regression analysis was used to describe the association of PCDD/F and PCB in maternal blood or milk with the outcome measurements after adjustment for confounding. Blood levels (n=182) of WHO 2005 toxic equivalents (TEQ) (PCDD/F+PCB) were in the range of 3.8-58.4 pg/glipid base (median: 19.3 pg/glipid base). The corresponding data for human milk (n=149) were 2.6-52.4 pg/glipid base (median: 19.7 pg/glipid base). Multiple regression analysis showed no decrease of thyroid hormones related to WHO 2005 TEQ in blood and milk of mothers and their newborns. Furthermore, no associations between exposure and neurological and developmental measures were observed. This study supports the view that the current decreased exposure to PCDD/Fs and PCBs does not impair thyroid function of newborns and neurodevelopment of infants until the age of 24 months. 相似文献
995.
* Barley (Hordeum vulgare) is a host for Blumeria graminis f. sp. hordei (Bgh), which causes powdery mildew, and for the rice blast pathogen Magnaporthe oryzae. It has previously been shown that Rar1, initially identified in a mutational screen as being required for Mla12-specified Bgh-resistance, also controlled pathogenic growth of M. oryzae in barley. Here, we tested whether the rom1 mutation (restoration of Mla12-specified resistance), which restored resistance against Bgh in a susceptible rar1-2 genetic background, also influences the interaction between barley and M. oryzae. * Disease severity after infection with M. oryzae was analysed on rar1-2 mutants and rar1-2 rom1 double mutants. Microscopy and northern analysis were used to gain insight into cellular and molecular events. * On rar1-2 rom1 double mutant plants, the number of M. oryzae disease lesions was increased in comparison to the wild-type and the rar1-2 mutant which correlated with augmented epidermal penetration. However, a decrease in the lesion diameter, apparently conditioned in the mesophyll, was also observed. * These results highlight the impact of Rom1 in basal defence of barley against different pathogens. Importantly, a tissue-specific function for Rom1 with contrasting effects on epidermal and mesophyll defence was demonstrated. 相似文献
996.
Kaminski T Siebrasse JP Gieselmann V Kubitscheck U Kappler J 《Glycoconjugate journal》2008,25(6):555-560
Hyaluronan is an important soluble component of the extracellular matrix of many tissues with well known space-filling, lubricating
and signaling functions. As such, hyaluronan can regulate cell adhesion, migration, differentiation and proliferation. Ultrastructural
studies showed the existence of fibers and networks of hyaluronan molecules at surfaces, while bulk studies of hyaluronan
in solution indicated that the polymer forms random coils. Here, we show that single hyaluronan molecules can be visualized
and tracked in three-dimensional samples at room temperature in aqueous buffer. Using a wide-field fluorescence microscope
equipped with laser excitation and an sensitive and fast EMCCD camera for fluorescence detection, single FITC-labeled hyaluronan
molecules from rooster comb were detected in aqueous solutions. Freely moving hyaluronan-FITC could be tracked over up to
20 images acquired at a frame rate of 98 Hz. Analysis of the trajectories revealed Brownian motion of hyaluronan in tris-buffered
saline with an average diffusion coefficient D = 3.0 ± 0.2 μm2/s. These observations confirm the concept that hyaluronan molecules form random coils in solution. The possibility of following
the tracks of single hyaluronan molecules in solution facilitates the analysis of processes that lead to the formation of
more organized forms of hyaluronan and its interactions with cells with very high spatial and temporal accuracy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
997.
Debarati Paul Neha Rastogi Ulrich Krauss Michael Schlomann Gunjan Pandey Janmejay Pandey Anuradha Ghosh Rakesh K. Jain 《Indian journal of microbiology》2008,48(2):279-286
Ring hydroxylating dioxygenases (RHDOs) are one of the most important classes of enzymes featuring in the microbial metabolism
of several xenobiotic aromatic compounds. One such RHDO is benzenetriol dioxygenase (BtD) which constitutes the metabolic
machinery of microbial degradation of several mono- phenolic and biphenolic compounds including nitrophenols. Assessment of
the natural diversity of benzenetriol dioxygenase (btd) gene sequence is of great significance from basic as well as applied study point of view. In the present study we have evaluated
the gene sequence variations amongst the partial btd genes that were retrieved from microorganisms enriched for PNP degradation from pesticide contaminated agriculture soils.
The gene sequence analysis was also supplemented with an in silico restriction digestion analysis. Furthermore, a phylogenetic analysis based on the deduced amino acid sequence(s) was performed
wherein the evolutionary relatedness of BtD enzyme with similar aromatic dioxygenases was determined. The results obtained
in this study indicated that this enzyme has probably undergone evolutionary divergence which largely corroborated with the
taxonomic ranks of the host microorganisms. 相似文献
998.
V. Carolina Figueroa Helland Svetlana Postnova Udo Schwarz Jürgen Kurths Bernd Kundermann Ulrich Hemmeter Hans A. Braun 《Journal of biological physics》2008,34(3-4):393-404
In healthy subjects, sleep has a typical structure of three to five cyclic transitions between different sleep states. In major depression, this regular pattern is often destroyed but can be reestablished during successful treatment. The differences between healthy and abnormal sleep are generally assessed in a time-consuming process, which consists of determining the nightly variations of the sleep states (the hypnogram) based on visual inspection of the electroencephalogram (EEG), electrooculogram, and electromyogram. In this study, three different methods of sleep EEG analysis (spectrum, outlier, and recurrence analysis) have been examined with regard to their ability to extract information about treatment effects in patients with major depression. Our data suggest that improved sleep patterns during treatment with antidepressant medication can be identified with an appropriate analysis of the EEG. By comparing different methods, we have found that many treatment effects identified by spectrum analysis can be reproduced by the much simpler technique of outlier analysis. Finally, the cyclic structure of sleep and its modification by antidepressant treatment is best illustrated by a non-linear approach, the so-called recurrence method. 相似文献
999.
Eckstein J Verheule S de Groot NM de Groot N Allessie M Schotten U 《Progress in biophysics and molecular biology》2008,97(2-3):435-451
The progressive nature of atrial fibrillation (AF) has been demonstrated in numerous experimental as well as clinical investigations. Electrical remodeling (shortening of atrial refractoriness) develops within the first days of AF and contributes to the increase in stability of the arrhythmia. However, "domestication of AF" must also depend on other mechanisms since the stability of AF continues to increase after electrical remodeling has been completed. Chronic atrial stretch induces activation of numerous signaling pathways leading to cellular hypertrophy, fibroblast proliferation and tissue fibrosis. The resulting electro-anatomical substrate is characterized by increased non-uniform anisotropy and local conduction heterogeneities facilitating reentry in the dilated atria. Atrial fibrosis may lead to disruption of the electrical side-to-side junctions between muscle bundles. This can result in electrical dissociation between neighboring muscle bundles, i.e. they become activated out-of-phase. Recent mapping studies in goats with persistent AF showed that electrical dissociation can not only occur between neighboring muscle bundles but also in the third dimension, i.e. between the epicardial layer and the endocardial bundle network. Such endo-epicardial dissociation will significantly increase the number of wavefronts which can simultaneously be present in the atrial wall. This article reviews data suggesting a role of endo-epicardial dissociation in dilated and fibrillating atria, for the self-perpetuating nature of AF as well as its possible implications for therapeutic interventions. 相似文献
1000.
Diversity and Activity of Cellulose-Decomposing Bacteria,Isolated from a Sandy and a Loamy Soil after Long-Term Manure Application 总被引:1,自引:0,他引:1
The community of culturable cellulolytic bacteria was analyzed in two long-term experimental field sites on Albic Luvisol
(silty sand) and Haplic Phaeozem (loam), with and without farmyard manure treatment. Against the backdrop of significant differences
in soil properties, the bacterial community structure differed clearly between sites and was affected by manure application
as analyzed by T-RFLP of 16S rDNA. The population densities of cellulolytic bacteria were significantly increased by manure
application in Phaeozem. Cellulose decomposing potentials of 537 isolates were tested on soluble, colloidal, and crystalline
cellulose. The results showed some evidence of a greater proportion of isolates with high decomposition activity in Luvisol,
but no impact from manure application could be observed in both soils. Restriction analysis and sequencing of 16S rDNA of
isolates revealed a rather simple community composition that was dominated by Streptomyces (67%). The composition of the RFLP groups was affected by manure application, which was most evident in Luvisol, whereas
an effect of the soil type could not be found. Although abundant RFLP groups were assigned to phylogenetically different bacterial
classes (Actinobacteria, Betaproteobacteria, and Gammaproteobacteria), cellulolytic activity could not consistently be differentiated. All in all, cellulolytic capabilities of the isolates were
highly variable and did not map to phylogenetic affiliation. 相似文献