共查询到20条相似文献,搜索用时 31 毫秒
1.
Lin M Wang X Zhu J Fan D Zhang Y Zhang J Guo Z 《Apoptosis : an international journal on programmed cell death》2011,16(3):288-300
Polynuclear platinum(II) complexes represent a class of potential anticancer agents that have shown promising pharmacological
properties in preclinical studies. The nature of cellular responses induced by these complexes, however, is poorly understood.
In this research, the cellular responses of human ovarian cancer COC1 cells to dinuclear platinum(II) complexes {[cis-Pt(NH3)2Cl]2L1}(NO3)2 (1) and {[cis-Pt(NH3)2Cl]2L2}(NO3)2 (2) (L1 = α,α′-diamino-p-xylene, L2 = 4,4′-methylenedianiline) has been studied using cisplatin as a reference. The effect of platinum complexes on the proliferation,
death mode, mitochondrial membrane potential, and cell cycle progression has been examined by MTT assay and flow cytometry.
The activation of cell cycle checkpoint kinases (CHK1/2), extracellular signal-regulated kinases (ERK1/2), and p38 mitogen-activated
protein kinase (p38 MAPK) of the cells by the complexes has also been analyzed using phospho-specific flow cytometry. Complex
1 is more cytotoxic than complex 2 and cisplatin at most concentrations; complex 2 and cisplatin are comparably cytotoxic. These complexes kill the cells through an apoptotic or apoptosis-like pathway characterized
by exposure of phosphatidylserine and dissipation of mitochondrial membrane potential. Complex 1 shows the strongest inductive effect on the morphological changes of the cells, followed by cisplatin and complex 2. Complexes 1 and 2 arrest the cell cycle in G2 or M phase, while cisplatin arrests the cell cycle in S phase. The influence of these complexes
on CHK1/2, ERK1/2, and p38 MAPK varies with the dose of the drugs or reaction time. Activation of phospho-ERK1/2 and phospho-p38
MAPK by these complexes is closely related to the cytostatic activity. The results demonstrate that dinuclear platinum(II)
complexes can induce some cellular responses different from those caused by cisplatin. 相似文献
2.
Lukas K. Filak Gerhard Mühlgassner Michael A. Jakupec Petra Heffeter Walter Berger Vladimir B. Arion Bernhard K. Keppler 《Journal of biological inorganic chemistry》2010,15(6):903-918
The synthesis of ruthenium(II) and osmium(II) arene complexes with the closely related indolo[3,2-c]quinolines N-(11H-indolo[3,2-c]quinolin-6-yl)-ethane-1,2-diamine (L
1
) and N′-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (L
2
) and indolo[3,2-d]benzazepines N-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-ethane-1,2-diamine (L
3
) and N′-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-N,N-dimethylethane-1,2-diamine (L
4
) of the general formulas [(η6-p-cymene)MII(L
1
)Cl]Cl, where M is Ru (4) and Os (6), [(η6-p-cymene)MII(L
2
)Cl]Cl, where M is Ru (5) and Os (7), [(η6-p-cymene)MII(L
3
)Cl]Cl, where M is Ru (8) and Os (10), and [(η6-p-cymene)MII(L
4
)Cl]Cl, where M is Ru (9) and Os (11), is reported. The compounds have been comprehensively characterized by elemental analysis, electrospray ionization mass
spectrometry, spectroscopy (IR, UV–vis, and NMR), and X-ray crystallography (L
1
·HCl, 4·H2O, 5, and 9·2.5H2O). Structure–activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells as well as cyclin-dependent
kinase (cdk) inhibition and DNA intercalation in cell-free settings have been established. The metal-free indolo[3,2-c]quinolines inhibit cancer cell growth in vitro, with IC50 values in the high nanomolar range, whereas those of the related indolo[3,2-d]benzazepines are in the low micromolar range. In cell-free experiments, these classes of compounds inhibit the activity of
cdk2/cyclin E, but the much higher cytotoxicity and stronger cell cycle effects of indoloquinolines L
1
and 7 are not paralleled by a substantially higher kinase inhibition compared with indolobenzazepines L
4
and 11, arguing for additional targets and molecular effects, such as intercalation into DNA. 相似文献
3.
Hydraulic conductivity (Lp) of the plasma membrane of Chara corallina was inhibited by HgCl2 maximally by about 95%. The inhibition was reversed by 2-mercaptoethanol, reconfirming the observation obtained by Henzler and Steudle (1995). The results suggest that osmotic water transport through Chara cells occurs mostly via mercury-sensitive water channels containing thiol groups. ZnCl2 dissolved in APW (pH 5.6) also inhibited Lp by about 80% within 1–2 h, while ZnCl2 dissolved in Hepes-Tris buffer (pH 7.4) inhibited it by about 90% within several minutes. Inhibition of Lp by ZnCl2 was also reversed by 2-mercaptoethanol, suggesting that zinc acts also on thiol groups of water channel proteins. Cells from which tonoplast had been removed by ECTA were as sensitive to both HgCl2 and ZnCl2 (pH 7.4) as normal cells. This demonstrates that water channels sensitive to thiol reagents really exist in the plasma membrane. On the other hand, ZnCl2 (pH 5.6) did not inhibit Lp of tonoplast-free cells. This may be accounted for by assuming first that Hg- and Zn-sensitive thiol groups of water channels may exist on the cytoplasmic side, and second that ZnCl2 in acidic medium may exist in ionized species which can be chelated by EGTA after permeation. The polar water permeability, or the endoosmotic Lp being larger than the exoosmotic one, was not affected by lowering the rate of osmosis by decreasing the osmotic gradient for transcellular osmosis down to 0.02 M sorbitol. The polarity disappeared when osmotic water flow through water channels was completely inhibited by HgCl2. Thus the polarity is assumed to be intrinsic to water channels in the plasma membrane. 相似文献
4.
Ktitorova I. N. Skobeleva O. V. Sharova E. I. Ermakov E. I. 《Russian Journal of Plant Physiology》2002,49(3):369-380
Changes in the root diameter were measured in wheat, Triticum aestivum L., using a sensor of small displacements in osmotic experiments, and the hydraulic conductivity (L
p) of the root was calculated by the method of initial flows. The L
p decreased by two to three times during 30-min exposure in 0.1–9 mM H2O2. In 150 mM NaCl, changes in L
p exhibited two-phase kinetics: an initial increase in L
p by two and a half to three times, followed by a decrease to 1.6–50% of the control level within the subsequent 24 h. After one-day-long exposure of the roots in a solution containing 150 mM NaCl and 100 mg/l catalase, L
p did not differ from the control level. Root pretreatment with salicylate, which promotes the formation of H2O2, prevented the initial increase in L
p in 150 mM NaCl, probably, due to a drastic L
p decrease. The activity of guaiacol peroxidase in the roots increased by three times within the 20-min exposure of the roots to the salt solution. The data suggest that hydrogen peroxide can mediate the L
p decrease during the first day of salinity stress. 相似文献
5.
Yajaira Pérez Vilmari López Luis Rivera-Rivera Aracelis Cardona Enrique Meléndez 《Journal of biological inorganic chemistry》2005,10(2):94-104
Three new water soluble titanocene–aminoacid complexes have been synthesized via the reaction of Cp2TiCl2 and two equivalents of aminoacid (L) in methanol, affording [Cp2TiL2]Cl2, L=L-cysteine (2), D-penicillamine (3) and L-methionine (4). These complexes have been characterized by 1H, IR and UV-Vis spectroscopies, elemental analysis and cyclic voltammetry. Kinetic studies of ligand hydrolysis have been monitored at low pH using UV-Vis and 1H NMR spectroscopies to assess their stability in aqueous solution. At low pH, aminoacid ligands are lost one order of magnitude faster than cyclopentadienyl. However, at physiological pH, in Tris buffer solution, the complexes decompose rapidly to form an insoluble titanium compound. The affinity of these complexes to apo-transferrin was also investigated to elucidate how the ancillary aminoacid ligands affect the titanium intake by apo-transferrin.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
6.
《Molecular membrane biology》2013,30(1-2):21-35
The effect of cholesterol depletion on potassium tracer fluxes was studied in sheep red cells. Removal by the plasma incubation method (5, 12, 30) of approximately 31 and 34% membrane cholesterol from high-potassium (HK) and low-potassium (LK) sheep red cells, respectively, did not induce significant changes in the steady-state cation composition of these cells nor in their passive (leak) and active (pump) K+ influxes. In cholesterol-depleted LK sheep red cells, there was no impairment nor augmentation of the Lp an tibody stimulated K+ pump flux and L1-antibody-mediated reduction of K+ leak flux indicating that the removed cholesterol does not contribute to the activity of the Lp and L1 antigens. 相似文献
7.
In the present paper, we have presented a theoretical discussion of specific biophysical mechanisms pertaining to the regulation
(by means of internal factors) of physiological water exchange with the water medium by the cells of the Nitella translucens. The investigation has demonstrated that these cells have a capacity for water exchange regulation through changes in the
values of transport parameters of the cell membrane (i.e. the filtration coefficient Lp and the reflection coefficient σ), as well as changes in the concentration Csi (inside the cells) of the osmotically active solute. 相似文献
8.
Ernest M. Wright Anthony P. Smulders John D. Tormey 《The Journal of membrane biology》1972,7(1):198-219
Summary Osmotic water flows were measured acrossin vitro preparations of the rabbit gallbladder by a gravimetric technique. The bladders exhibited asymmetrical osmotic behavior, in which theL
p
(hydraulic conductivity) for water flow from mucosa to serosa was up to four times greater than theL
p
for water flow in the opposite direction. This result is similar to the effects of osmotic gradients on ion and nonelectrolyte permeability reported in the first paper. As in the case of solute permeability, these changes inL
p
are accounted for by changes in the dimensions of the lateral intercellular spaces of the epithelium. These spaces are thus a final common pathway for the movement of both solutes and water across the epithelium. We also observed osmotic flow transients in which the initialL
p
was about an order of magnitude greater than the steady stateL
p
. These transients are largely explained by solute polarization in the unstirred layers adjacent to the epithelial membranes. A comparison between streaming potentials and water flows showed that streaming potentials are directly proportional to the rate of flow only over a limited range. These observations are readily explained on the basis of structural changes and solute polarization effects. Finally, the routes of water flow across epithelia are discussed in the light of our observations. 相似文献
9.
Katarzyna Kulinska Tadeusz Kulinski Jacek Stawinski Aatto Laaksonen 《Journal of biomolecular structure & dynamics》2013,31(5):987-998
Abstract The hydration pattern of thymidyl(3′→5′) thymidine 1 and those of Rp and Sp diastereomers of the corresponding methylphosphonate analogue 2, have been studied using Molecular Dynamics (MD) computer simulation. It was found that the methylphosphonate modification leads to significant changes in the coordination of water molecules around the internucleotidic linkage and these, in turn, affect the hydration pattern of other parts of the molecule. The most notable differences between Rp and Sp diastereomers 2a and 2b were found to occur at the deoxyribose moieties of the nucleosid-5′-yl units. 相似文献
10.
11.
Elvira Cuenllas Soledad Gaitan Juan A. Bueren Concepcion Tejero 《Bioscience reports》1990,10(2):141-154
Pyruvate kinase studies in the granulocyte-macrophage lineage duringin vitro differentiation have been performed using culture techniques on GM-CFC cells and a study has also been done in bone marrow cells.The enzyme exhibits biphasic behaviour with respect to both of its substrates in cells derived fromin vitro cultures at 5 and 7 days of incubation period. However in bone marrow cells these kinetics are only observed for ADP.The different kinetic behaviour of pyruvate kinase toward Fru-1,6-P2, Ala, Phe and ATP in the three cellular populations allows us to conclude that the expression of pyruvate kinase is associated with the differentiation of these cells.Abbreviations GM-CFC
granulocyte-macrophage colony forming cells
- PK
pyruvate kinase
- CFU-E
Colony Forming Units Erythroid
- Ew
Error weight
- PEP
phosphoenolpyruvate
- Fru-1,6-P2
fructose 1,6-bisphosphate
- Ala
L-alanine
- Phe
L-phenylanine
- 5 GM
granulocytemacrophage colonies obtained after 5 days incubation
- 7 GM
granulocyte-macrophage colonies obtained after 7 days incubation
- h
Hill coefficient
- S0,5
substrate concentration that yields half-maximal velocity 相似文献
12.
Partial pressure of CO2 (pCO2) and iron availability in seawater show corresponding changes due to biological and anthropogenic activities. The simultaneous change in these factors precludes an understanding of their independent effects on the ecophysiology of phytoplankton. In addition, there is a lack of data regarding the interactive effects of these factors on phytoplankton cellular stoichiometry, which is a key driving factor for the biogeochemical cycling of oceanic nutrients. Here, we investigated the effects of pCO2 and iron availability on the elemental composition (C, N, P, and Si) of the diatom Pseudo‐nitzschia pseudodelicatissima (Hasle) Hasle by dilute batch cultures under 4 pCO2 (~200, ~380, ~600, and ~800 μatm) and five dissolved inorganic iron (Fe′; ~5, ~10, ~20, ~50, and ~100 pmol · L?1) conditions. Our experimental procedure successfully overcame the problems associated with simultaneous changes in pCO2 and Fe′ by independently manipulating carbonate chemistry and iron speciation, which allowed us to evaluate the individual effects of pCO2 and iron availability. We found that the C:N ratio decreased significantly only with an increase in Fe′, whereas the C:P ratio increased significantly only with an increase in pCO2. Both Si:C and Si:N ratios decreased with increasing pCO2 and Fe′. Our results indicate that changes in pCO2 and iron availability could influence the biogeochemical cycling of nutrients in future oceans with high‐ CO2 levels, and, similarly, during the time course of phytoplankton blooms. Moreover, pCO2 and iron availability may also have affected oceanic nutrient biogeochemistry in the past, as these conditions have changed markedly over the Earth's history. 相似文献
13.
A new method for the determination of hydraulic conductivity and cell volume of plant cells by pressure clamp 总被引:5,自引:0,他引:5
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Internodes of Chara corallina were used for experiments in which cell turgor pressure was clamped by means of the pressure probe technique. Essentially, the procedure consisted of a combination of volume and turgor pressure relaxations. This technique permits the determination of the cell volume by nonoptical means. The values obtained are in agreement with the ones determined by optical means. Furthermore, the hydraulic conductivity (Lp) was determined from the initial slope of the volume relaxation; the values thus obtained are in agreement with those calculated from the half-times of pressure relaxations. The determination of Lp from volume relaxation measurements has the advantage that the cell volume, the volumetric elastic modulus of the cell wall, and the internal osmotic pressure do not have to be known. Furthermore, the half-time of volume relaxation is longer than that of pressure relaxation, as shown by theory and experiment. This may be used to enhance the resolution of the relaxation measurement and, thus, to improve the accuracy of Lp determinations for higher plant cells which exhibit a very fast pressure relaxation. 相似文献
14.
Giordano C Lucente G Masi A Paglialunga Paradisi M Sansone A Spisani S 《Amino acids》2007,33(3):477-487
Summary. For-Met-βAlaψ[CSNH]-Phe-OMe (3), For-Met-βAlaψ[CH2NH]-Phe-OMe (5), For-Met-NH-pC6H4-SO2-Phe-OMe (8a), For-Met-NH-mC6H4-SO2-Phe-OMe (8b) and the corresponding N-Boc precursors (2, 4, 7a, b) have been synthesized and their activity towards human neutrophils has been evaluated in comparison with that shown by the
reference tripeptide For-Met-Leu-Phe-OMe (fMLF-OMe). Chemotaxis, lysozyme release and superoxide anion production have been
measured. 1H NMR titration experiments and IR spectra have been discussed in order to ascertain the preferred solution conformation adopted
by the tripeptide 3 with particular reference to the presence of a folded conformation centred at the centrally positioned thionated β-residue. 相似文献
15.
Vivek K. Sharma Sunil K. Singh Kapil Bohra Chandra Shekhar Reddy L. Vinod Khatri Carl E. Olsen 《Nucleosides, nucleotides & nucleic acids》2013,32(5):256-272
Three LNA-based mercaptoacetamido-linked nonionic nucleoside dimers TL-S-T, T-S-TL , and TL-S-TL have been synthesized by HOBT and HBTU catalyzed condensation of silyl-protected 2-S-(thymidin-5?′-yl)mercaptoacetic acid or 2-S-(2?′-O,4?′-C-methylenethymidin-5?′-yl)mercaptoacetic acid with 3?′-amino-3?′-deoxy-5?′-O-DMT-2?′-O,4?′-C-methylenethymidine or with 3?′-amino-3?′-deoxy-5?′-O-DMT-β-thymidine followed by desilylation of the protected dimers. The 3?′-O-phosphoramidite derivative of one of the nucleoside dimers was successfully prepared by condensation with [P(-Cl)(-OCH2CH2CN)-N(iPr)2}] in DCM in the presence of N,N-diisopropylethylamine (DIPEA), which is a building block for the preparation of mercaptoacetamido-linked oligonucleotides of therapeutic applications. 相似文献
16.
Yoshio Sugiyama Kazuaki Kitano Toshihiko Kanzaki 《Bioscience, biotechnology, and biochemistry》2013,77(8):1837-1847
Cell-free extracts of Brevibacterium thiogenitalis culture grown in the presence of copper catalyzed the oxidation of NADH2 and succinate through an electron transport chain which contained menaquinones and cytochromes a, b and c. On the other hand, extracts of cells grown in the absence of copper lacked cytochromes a and c, and contained cytochrome d.These findings, as well as the results obtained in inhibition experiments, suggest that in copper-deficient cells the major part of NADH2 was oxidized via a bypass in which the electrons were transferred directly from flavoprotein or cytochrome b to molecular oxygen.Electron transport from these substrates to molecular oxygen resulted in ATP synthesis. The average P/O ratios in extracts of the copper-sufficient cells were 0.33 for generated NADH2, 0.20 for added NADH2, and 0.34 for succinate, and those in extracts of the copper-deficient cells were 0.15, 0.13 and 0.21, respectively. In addition, a linear relationship was found between the yield of L-glutamate from acetate and the P/Ο ratios with both NADH2 and succinate as substrates.From these results, it is reasonable to consider that the poor yield of L-glutamate from acetate in copper-deficient cells was due to a reduction in energy supply, which was caused by the low efficiency of oxidative phosphorylation. 相似文献
17.
Long-term cryopreservation of islets of Langerhans would be advantageous to a clinical islet transplantation program. Fundamental cryobiology utilizes knowledge of basic biophysical characteristics to increase the understanding of the preservation process and possibly increase survival rate. In this study several of these previously unreported characteristics have been determined for individual islet cells isolated from Golden hamster islets. Using an electronic particle counting device and a temperature control apparatus, dynamic volumetric response of individual islet cells to anisosmotic challenges of 1.5 M dimethyl sulfoxide (DMSO) and 1.5 M ethylene glycol (EG) were recorded at four temperatures (8, 22, 28, and 37°C). The resulting curves were fitted using Kedem and Katchalsky equations which describe water flux and cryoprotectant agent (CPA) flux based on hydraulic conductivity (Lp), CPA permeability (Ps), and reflection coefficient (?) for the membrane. For Golden hamster islet cells,Lp,Ps, and ? for DMSO at 22°C were found to be 0.23 ± 0.06 μm/min/atm, 0.79 ± 0.32 × 10−3cm/min, and 0.55 ± 0.37 (n= 11) (mean ± SD), respectively. For EG at 22°C,Lpequaled 0.23 ± 0.06 μm/min/atm,Psequaled 0.63 ± 0.20 × 10−3cm/min, and ? was 0.75 ± 0.17 (n= 9). Arrhenius plots (lnLpor lnPsversus 1/temperature (K)) were created by adding the data from the other three temperatures and the resulting linear regression yielded correlation coefficients (r) of 0.99 for all four plots (LpandPsfor both CPAs). Activation energies (Ea) ofLpandPswere calculated from the slopes of the regressions. The values for DMSO were found to be 12.43 and 18.34 kcal/mol forLpandPs(four temperatures, totaln= 52), respectively. For EG,EaofLpwas 11.69 kcal/mol andEaofPswas 20.35 kcal/mol (four temperatures, totaln= 58). 相似文献
18.
An understanding of cell osmotic behavior and membrane transport properties is indispensable for cryobiology research and development of cell-type-specific, optimal cryopreservation conditions. A microfluidic perfusion system is developed here to measure the kinetic changes of cell volume under various extracellular conditions, in order to determine cell osmotic behavior and membrane transport properties. The system is fabricated using soft lithography and is comprised of microfluidic channels and a perfusion chamber for trapping cells. During experiments, rat basophilic leukemia (RBL-1 line) cells were injected into the inlet of the device, allowed to flow downstream, and were trapped within a perfusion chamber. The fluid continues to flow to the outlet due to suction produced by a Hamilton Syringe. Two sets of experiments have been performed: the cells were perfused by (1) hypertonic solutions with different concentrations of non-permeating solutes and (2) solutions containing a permeating cryoprotective agent (CPA), dimethylsulfoxide (Me2SO), plus non-permeating solute (sodium chloride (NaCl)), respectively. From experiment (1), cell osmotically inactive volume (Vb) and the permeability coefficient of water (Lp) for RBL cells are determined to be 41% [n = 18, correlation coefficient (r2) of 0.903] of original/isotonic volume, and 0.32 ± 0.05 μm/min/atm (n = 8, r2 > 0.963), respectively, for room temperature (22 °C). From experiment (2), the permeability coefficient of water (Lp) and of Me2SO (Ps) for RBL cells are 0.38 ± 0.09 μm/min/atm and (0.49 ± 0.13) × 10−3 cm/min (n = 5, r2 > 0.86), respectively. We conclude that this device enables us to: (1) readily monitor the changes of extracellular conditions by perfusing single or a group of cells with prepared media; (2) confine cells (or a cell) within a monolayer chamber, which prevents imaging ambiguity, such as cells overlapping or moving out of the focus plane; (3) study individual cell osmotic response and determine cell membrane transport properties; and (4) reduce labor requirements for its disposability and ensure low manufacturing costs. 相似文献
19.
Mohd. Afzal Hamad A. Al-Lohedan Mohammad Usman 《Journal of biomolecular structure & dynamics》2019,37(6):1494-1510
Due to the critical role of cellular enzymes necessary for cell proliferation by deciphering topological hurdles in the process of DNA replication, topoisomerases have been one of the major targets in the anticancer drug development area. A need, therefore, arises for new metallodrugs that specifically recognizes DNA and inhibits the activity of topoisomerase enzymes, herein, we report the synthesis and characterization of new metal-based glycoconjugate entities containing heterobimetallic core CuII–SnIV (1) and NiII–SnIV (2) derived from N-glycoside ligand (L). The optimized structure of complex 1 and other significant vibrational modes have been explained using dispersion corrected B3LYP/DFT calculations. In vitro DNA binding profile of the L and both the complexes 1 and 2 were done by various biophysical studies. Complex 1 breaks pBR322 DNA via a hydrolytic means which was validated by T4 DNA enzymatic assay. To get a mechanistic insight of mode of action topoisomerase I (Topo I) inhibition assay was carried out. Also, we have taken the help of molecular modeling studies in accordance with experimental findings. In vitro cytotoxicity of the complex 1 was evaluated against a panel of cancer cells which exhibited remarkably good anticancer activity (GI50 values <10 μg/ml). Moreover, intracellular localization of the complex 1 was visualized by confocal microscopy against HeLa cells. 相似文献
20.
Pleurotus florida (ITCC 3308) produces two laccase enzymes (L1 and L2) in potato-dextrose media containing 0.5% yeast extract. Concentrated culture filtrate was separated on DEAE-Sephadex (A-50)
column into two enzyme peaks, subsequently named L1 and L2. The L1 enzyme has been purified to homogeneity by ion-exchange and gel-permeation chromatography. L1 is a monomeric glycoprotein with a molar mass of 77 and 82 kDa as determined by SDS-PAGE and gelfiltration chromatography,
respectively. The pI value of L1 has been determined to be 4.1. The optimum reaction temperature of the enzyme is 50°C. TheK
m and some other kinetic parameters of L1 have been determined. Cyanide and azide completely inhibit the enzyme activity. The enzyme was fully active in 1: 1 (V/V) buffer-chloroform for at least 2 h. Spectroscopic analysis revealed that the enzyme has four copper atoms, a type 1 copper,
a type 2 copper and a type 3 binuclear copper. 相似文献