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1.
The ability of a number of nitrogen-containing compounds that simultaneously carry the adamantane and monoterpene moieties to inhibit Tdp1, an important enzyme of the DNA repair system, is studied. Inhibition of this enzyme has the potential to overcome chemotherapeutic resistance of some tumor types. Compound (+)-3c synthesized from 1-aminoadamantane and (+)-myrtenal, and compound 4a produced from 2-aminoadamantane and citronellal were found to be most potent as they inhibited Tdp1 with IC50 values of 6 and 3.5 µM, respectively. These compounds proved to have low cytotoxicity in colon HCT-116 and lung A-549 human tumor cell lines (CC50 > 50 µM). It was demonstrated that compound 4a at 10 µM enhanced cytotoxicity of topotecan, a topoisomerase 1 poison in clinical use, against HCT-116 more than fivefold and to a lesser extent of 1.5 increase in potency for A-549. 相似文献
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Reuben S.E. Young Andrew P. Bowman Kaylyn D. Tousignant Berwyck L.J. Poad Jennifer H. Gunter Lisa K. Philp Colleen C. Nelson Shane R. Ellis Ron M.A. Heeren Martin C. Sadowski Stephen J. Blanksby 《Journal of lipid research》2022,63(6):100223
The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics. 相似文献
4.
Summary Cytoplasm-enriched fragments prepared from internodal cells ofChara corallina by centrifugation contain membrane bound vesicles ranging in size from a few m to hundreds of m. If the fragments are incubated in artificial pond water (APW) of pH0 above 6.5, neutral red stains the inside of many vesicles bright crimson, suggesting the presence of inward proton-pumping. In APW of pH0 below 6 crimson vesicles are found less frequently. Under such conditions most vesicles remain unstained inside and some develop indistinct pink halos. After a few days most fragments form a central vacuole, which stains red, regardless of the pH0. The cytoplasmic layer still contains vesicles after vacuole formation.In order to identify the membrane bounding the vesicles various fluorescent probes were applied either by injection into the fragment or directly onto the vesicles released into artificial cytoplasm. Lucifer yellow or 6 COOH-F move readily across the tonoplast in intact cells, but did not enter any vesicles. On the other hand, the fluorescent cationic stain DIOC, which is used to highlight mitochondria and especially endoplasmic reticulum, stained the vesicle membrane. Numerous elliptical or kidney shaped nuclei in the flowing cytoplasm were highlighted with DAPI. In some fragments the nuclei formed large agreggates sometimes filling the width of the fragment.Patch-clamping the vesicles in artificial cytoplasm showed the presence of several kinds of channels, some displaying similar behaviour to the K+ channels observed in cytoplasmic droplets.Analogous to the plasmalemma of intact cells, the fragments without vacuoles displayed electrophysiological states dominated by either K+ conduction, H+ (or OH–) conduction or the proton pump. On the other hand, excitation transients in fragments were of low amplitude or absent altogether. Detailed comparisons of data from fragments and intact cells are shown. The effect of vacuole formation on fragment electrophysiology was also explored. 相似文献
5.
Dr. Hansjörg Wunderer Serge Picaud Nicolas Franceschini 《Cell and tissue research》1989,257(3):565-576
Summary Single photoreceptor cells in the compound eye of the housefly Musca domestica were selectively illuminated and subsequently compared electron-microscopically with the unilluminated photoreceptors in the immediate surroundings. The rhabdomeres of the illuminated cells remain largely unaffected, but the cells show an increase in the number of coated pits, various types of vesicles, and degradative organelles; some of the latter organelles are described for the first time in fly photoreceptors. Coated pits are found not only at the bases of the microvilli, but also in other parts of the plasma membrane. Degradative organelles, endoplasmic reticulum (ER) and mitochondria aggregate in the perinuclear region. The rough ER and smooth ER are more elaborate, the number of Golgi stacks, free ribosomes and polysomes is increased, and the shape and distribution of heterochromatin within the nuclei are altered. Illuminated photoreceptors also interdigitate extensively with their neighbouring secondary pigment cells. These structural changes in illuminated fly photoreceptor cells indicate an increase in membrane turnover and cellular metabolism. When applied to the eye, Lucifer Yellow spreads into the extracellular space and is taken up only by the illuminated photoreceptor cells. These cells show the same structural modifications as above. Horseradish peroxidase applied in the same way is observed in pinocytotic vesicles and degradative organelles of the illuminated cells. Hence, the light-induced uptake of extracellular compounds takes place in vivo at least partially as a result of an increase in pinocytosis. 相似文献
6.
Andrew Clarke J. Cynan Ellis-Evans Mark W. Sanders Lesley J. Holmes 《Hydrobiologia》1989,172(1):183-191
The copepod Pseudoboeckella poppei (Daday) (Calanoida, Centropagidae) was sampled from Sombre and Heywood Lakes on Signy Island, Antarctica (60° S, 45° W) between January 1984 and March 1985. Sombre Lake is clear and oligotrophic with little phytoplankton and a bottom sediment low in organic content. By contrast Heywood Lake is turbid and mesotrophic; a substantial phytoplankton develops in summer and the bottom sediments are comparatively rich in organics. Both lakes freeze over for much of the year, forcing the copepods to adopt a benthic feeding strategy over winter. Adult Pseudoboeckella feed on phytoplankton when this is available, but also on detritus, diatoms and short algal filaments stirred up from the sediment. In Heywood Lake, male copepods show a smooth seasonal trend in lipid content with lipid being synthesised in early summer and utilised in late summer and winter. The summer increase in lipid content is associated with an increase in dry weight. Female lipid contents show evidence of two peaks of egg production. In Sombre Lake both male and female copepods increase in size during summer and show a wider range of lipid contents than in Heywood Lake; it is likely that this is due to the poorer winter feeding conditions which necessitate the synthesis of a much larger store of reserves during the summer. In contrast to marine calanoid copepods, lipid stores are exclusively triacylglycerol with no trace of wax ester. 相似文献
7.
To study the potential relationship between circulating triacylglycerol (TAG) levels and lipoprotein lipase (LPL) activity in the newborn rat liver, pups from undernourished or normal control mothers were nursed by normal dams, and studied at 0, 1, 15 or 30 days of age. Plasma TAG levels and liver TAG concentration increased more in pups from undernourished mothers than they did in controls. At birth, liver LPL activity was similarly high in both groups but, whereas in controls it decreased progressively after birth, in pups from undernourished mothers it remained stable until 15 days of age. Results suggest that the hypertriglyceridemia present in pups from undernourished mothers may be responsible for the sustained high LPL activity in their liver which may enhance the hepatic uptake of circulating TAG. 相似文献
8.
In the subarctic moss Dicranum elongatum Schleich & Schwaegr., the level of total lipids and triacylglycerols (TAG) was high in late winter and spring and low in autumn and winter. Four-week exposure of field material to continuous light (135μmol m−2 s−1 ) at 1°C resulted in a considerable increase in the amount of TAG in the autumn material acclimated to low temperatures and rhythmic light in the field. In contrast, the same treatment did not cause any increase in TAG in the spring material, acclimated to low temperatures and continuous light in the field. Results from experiments, in which moss cultivated for 4 months at 9°C on 12-h photoperiods (135μmol m−2 s−1 ) was kept for 3 weeks at low temperatures (9°C and −3°C) either in continuous light (135 or 70 μmol m−2 s−1 ) or with 12-h photoperiods (135 μmol m−2 s−1 ), indicated that the TAG level was higher at higher light intensity. At 9°C it was also higher in continuous light of both intensities than in rhythmic light. These results strongly suggest that decreasing irradiance and decreasing daylength limits the accumulation of TAG in D. elongatum during autumn in the subarctic. 相似文献
9.
Boronic acid derivatives of good peptide substrates of the serine proteases cause slow-binding inhibition, manifested as biphasic binding (Kettner and Shenvi: J. Biol Chem. 259:15106-15114, 1984). These inhibitors are thought to act as reaction-intermediate analogs. Three peptide boronic acids--Ac-Pro-boro-Val-OH, DNS-Ala-Pro-boro-Val-OH, and Ac-Ala-Ala-Pro-boro-Val-OH--were chosen for far-ultraviolet circular dichroism (CD) studies in order to determine whether the second phase involves a conformational change of pancreatic elastase. The dipeptide is a simple competitive inhibitor (Ki = 0.27 microM) and the latter are slow-binding inhibitors (Ki = 16.4 and 0.25 nM, respectively). Spectral deconvolution and correction for the formation of antiparallel beta-sheet by the peptide inhibitor itself indicate that there is no significant change in the secondary structure of the enzyme in either the initial or final inhibitor complex. A kinetic experiment confirmed that the slow-binding step was not associated with a CD spectral change, and that therefore a protein conformational change was not responsible for the slow binding. 相似文献
10.
Summary Two winter wheat genotypes (Diószegi 200 and Mv 15) were compared for their in vitro androgenic capacity. On average, the induction frequency of embryogenic structures was 71.7% in Diószegi 200 and only 4.3% in Mv 15. The haploid induction ability of the two genotypes differed considerably, with Diószegi 200 being much higher. The difference in the in vitro inductability of the microspores may result from genetic differences which are manifested in the survival rate of the microspores during the culture period and their adaptability to in vitro conditions. Special DNA fluorochrornes were suitable for studying the different pathways of in vitro androgenesis. Our data indicate that the repeated equal divisions of the microspore nucleus might lead to pollen embryo formation, and subsequent divisions of the vegetative portion of the pollen grain after the first asymmetric microspore mitosis can result in pollen callus formation. 相似文献