首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
The effects of ethanol and inositol 1,4,5-trisphosphate (IP3) on releasable Ca stores were examined in microsomes isolated from mouse whole brain. Ca release was monitored by determination of changes in the extra-microsomal Ca concentration using Indo-1, a fluorescent Ca indicator. In the absence of ATP, ethanol released Ca from microsomes in a concentration-dependent manner, with a threshold for Ca release between 25 and 50 mM. Ethanol-induced release of microsomal Ca was reduced by approximately 50% after ATP-stimulated uptake of Ca, indicating that the ethanol-releasable pool was diminished by ATP-dependent uptake of Ca into an ethanol-insensitive microsomal pool. Release of Ca produced by ethanol was linear with concentration (up to 400 mM). By contrast, IP3-induced Ca release was saturable and was dependent on prior ATP-stimulated Ca uptake. Simultaneous addition of ethanol and IP3 produced additive responses. These results show that pharmacologically relevant concentrations of ethanol release Ca from an IP3-insensitive intracellular Ca store. Furthermore, our results demonstrate the existence of at least two releasable stores of Ca in brain microsomes.  相似文献   

2.
Airway reactivity has been shown to vary with age; however, the mechanism(s) underlying this process remain unidentified. To elucidate the role of ontogenetic changes in phosphoinositide-linked signal transduction, we examined whether age-related differences in tracheal smooth muscle (TSM) contractility to carbachol (CCh) are associated with developmental changes in the production and metabolism of the second messenger, inositol 1,4,5-trisphosphate (Ins (1,4,5)P3). In TSM segments isolated from 2-wk-old and adult rabbits, both the maximal isometric contractile force and sensitivity (i.e., -logED50) to CCh (10(-10)-10(-4) M) were significantly greater in the immature vs. adult tissues (P less than 0.001). Similarly, Ins(1,4,5)P3 accumulation elicited by either receptor-coupled stimulation with CCh (10(-10)-10(-4) M) or post-receptor-mediated guanine nucleotide binding protein activation of permeabilized TSM with GTP gamma S (100 microM) was also significantly enhanced in 2-wk-old vs. adult TSM. Measurement of the activities of the degradative enzymes for Ins(1,4,5)P3 demonstrated that: (a) mean +/- SE maximal Ins(1,4,5)P3 3'-kinase activity was significantly reduced in the immature vs. adult TSM (i.e., approximately 71.7 +/- 6.0 vs. 137.8 +/- 10.0 pmol/min per mg protein, respectively; P less than 0.005); (b) by contrast, maximal Ins(1,4,5)P3 5'-phosphatase activity was significantly increased in the immature vs. adult TSM (i.e., 27.9 +/- 1.2 vs. 15.6 +/- 1.5 nmol/min per mg protein, respectively; P less than 0.001); and (c) the Km values for Ins(1,4,5)P3 5'-phosphatase were 14- and 19-fold greater than those for Ins(1,4,5)P3 3'-kinase in the 2-wk-old and adult TSM, respectively. Collectively, the findings suggest that the age-related decrease in agonist-induced rabbit TSM contractility is associated with a diminution in Ins(1,4,5)P3 accumulation which is attributed, at least in part, to ontogenetic changes in the relative activities of the degradative enzymes for Ins(1,4,5)P3.  相似文献   

3.
The present study examined the effect of chronic hypoxia on coupling efficiency of alpha-1 adrenoceptors to inositol 1,4,5-trisphosphate (InsP3) signaling in ovine uterine artery. Chronic hypoxia did not change the time course of InsP3 formation, but significantly decreased the potency (pD2: 6.17 +/- 0.09 --> 5.26 +/- 0.12) and the maximal response (220.7 +/- 21.7 --> 147.7 +/- 15.3 pmol/mg protein) of norepinephrine-induced InsP3 synthesis. The coupling efficiency of alpha-1 adrenoceptors to InsP3 synthesis (picomoles InsP3 per femtomoles receptor) was decreased 45% by chronic hypoxia. In addition, simultaneous measurement of norepinephrine-induced contractions and InsP3 synthesis indicated that for a given amount of InsP3 generated, the contractile force of the uterine artery was significantly less in chronically hypoxic than in control tissues (0. 27 +/- 0.01 versus 0.35 +/- 0.02 g tension/pmol InsP3). InsP3 receptors were characterized using radioligand binding techniques. Although the density of InsP3 receptors was not changed by chronic hypoxia (Bmax: 325 +/- 35 --> 378 +/- 18 fmol/mg protein), the dissociation constant (Kd) of InsP3 to its receptors was significantly increased (Kd: 5.20 +/- 0.40 --> 7.81 +/- 0.34 nM). Analysis of InsP3 receptor occupancy-tension development relationship indicated no difference in intrinsic ability of the InsP3-receptor complex in eliciting contractions between the control and hypoxic tissues. Our results suggest that chronic hypoxia attenuates coupling efficiency of alpha-1 adrenoceptors to InsP3 synthesis in the uterine artery. In addition, the tissue contractile sensitivity to InsP3 is reduced, which is mediated predominantly by a decrease in InsP3 binding affinity to InsP3 receptors.  相似文献   

4.
The proteasome inhibitor bortezomib is an emerging anticancer agent. Although the proteasome is clearly its locus of action, the early biochemical consequences of bortezomib treatment are poorly defined. Here, we show in cultured cells that bortezomib and other proteasome inhibitors rapidly inhibit free ubiquitin levels and ubiquitin thiolesterification to ubiquitin-conjugating enzymes. Inhibition of thiolesterification correlated with a reduction in the ubiquitination of certain substrates, exemplified by a dramatic decline in histone monoubiquitination and a decrease in the rate of inositol 1,4,5-trisphosphate receptor polyubiquitination. Thus, in addition to the expected effect of blocking the degradation of polyubiquitinated substrates, bortezomib can also inhibit ubiquitination. The effect of bortezomib on histone monoubiquitination may contribute to its therapeutic actions.  相似文献   

5.
The hypothalamic-pituitary-adrenal (HPA) axis has been shown to be involved in mood and behavior. The possibility that adrenal glucocorticoids regulate components of the phosphatidylinositol (PI) signal transduction pathway was investigated. Two different doses of corticosterone (CORT) pellets (50 or 100 mg) were implanted in normal and bilaterally adrenalectomized (ADX) rats, and CORT regulation of the expression of G(q) alpha protein, phospholipase C (PLC) isozymes, inositol 1,4,5-trisphosphate receptor (IP(3)R) isoforms, and of PI-PLC activity, [(3)H]IP(3) binding to IP(3)Rs, and IP(3) levels were measured in various brain areas after 1 or 14 days. Fourteen days of CORT pellet implantation into normal rats dose dependently decreased PI-PLC activity and selectively the mRNA and protein expression of PLC beta(1) isozyme in cortex and hippocampus. Bilateral ADX caused the opposite changes in these measures, and simultaneous CORT pellet implantation into ADX rats reversed these effects. Furthermore, 14 days of CORT treatment of normal rats increased [(3)H]IP(3) binding to IP(3)Rs and decreased IP(3) levels in cortex, hippocampus, and cerebellum, without any changes in expression of IP(3)R-I, IP(3)R-II, or IP(3)R-III isoform. On the other hand, ADX decreased [(3)H]IP(3) binding and increased levels of IP(3), and simultaneous CORT treatment of ADX rats prevented these changes. ADX or CORT treatment had no significant effects on the expression of G(q/11) alpha protein. These results suggest that manipulation of the HPA axis alters various components of the PI signaling pathway in rat brain, which may have physiological relevance to the HPA axis-mediated changes in mood and behavior.  相似文献   

6.
7.
The involvement of inositol 1,4,5-trisphosphate (IP(3)) formation in the voltage-dependent regulation of intracellular Ca(2+) concentration ([Ca(2+)](i)) was examined in smooth muscle cells of the porcine coronary artery. Slow ramp depolarization from -90 to 0 mV induced progressive [Ca(2+)](i) increase. The slope was reduced or increased in the presence of Cd(2+) or (±)-1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-[trifluoromethyl]-phenyl)pyridine-3-carboxlic acid methyl ester (Bay K 8644), respectively. The decrease in [Ca(2+)](i) via the membrane hyperpolarization induced by K(+) channel openers (levcromakalim and Evans blue) under current clamp was identical to that under voltage clamp. The step hyperpolarization from -40 to -80 mV reduced [Ca(2+)](i) uniformly over the whole-cell area with a time constant of ~10 s. The [Ca(2+)](i) at either potential was unaffected by heparin, an inhibitor of IP(3) receptors. Alternatively, [Ca(2+)](i) rapidly increased in the peripheral regions by depolarization from -80 to 0 mV and stayed at that level (~400 nM) during a 60-s pulse. When the pipette solution contained IP(3) pathway blockers [heparin, 2-aminoethoxydiphenylborate, xestospongin C, or 1-[6-[((17β)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U73122)], the peak [Ca(2+)](i) was unchanged, but the sustained [Ca(2+)](i) was gradually reduced by ~250 nM within 30 s. In the presence of Cd(2+), a long depolarization period slightly increased the [Ca(2+)](i), which was lower than that in the presence of heparin alone. In coronary arterial myocytes, the sustained increase in the [Ca(2+)](i) during depolarization was partly caused by the Ca(2+) release mediated by the enhanced formation of IP(3). The initial [Ca(2+)](i) elevation triggered by the Ca(2+) influx though voltage-dependent Ca(2+) channels may be predominantly responsible for the activation of phospholipase C for IP(3) formation.  相似文献   

8.
We have carried out the first systematic study of the effects of visible light on the homogenous dynamics in the bromate–sulfite–ferrocyanide (BSF) reaction. Under flow conditions, the reaction system displayed photoinduction and photoinhibition behavior, and the oscillatory period decreased with the increase of light intensity, which is due to the fact that light irradiation mainly enhanced the negative process and affected the positive feedback. The light effect on positive and negative feedback is studied by analyzing the period length of pH increasing and decreasing in detail. With the increase of light intensity, the period length of pH increasing decreases monotonically, while the period length of pH decreasing changes nonmonotonically. These results suggest that light could be used as a powerful tool to control homogenous dynamics. Results obtained from numerical simulations are in good agreement with experimental data.

The BSF reaction system displayed photoinduction and photoinhibition behavior under flow conditions. The oscillatory period decreased as the light irradiation mainly enhanced the negative process and affected the positive feedback.  相似文献   

9.
The phase assembly and microstructure of the aluminum-incorporated CaO–SiO2–H2O system, which is technologically important in autoclaved building materials, catalysis and waste management, were investigated using XRD, SEM, FTIR and NMR depending on aluminum addition, reaction temperature and curing time. The content of each phase was obtained using the MAUD program based on the Rietveld refinement. The results revealed that the formation of the tobermorite phase was promoted at Al/(Al + Si) ≤ 0.03, and subsequently retarded by higher aluminum addition, which was corroborated by the presence of more low polymerized and cross-linked (alumino)silicate chains. The phase purity decreased with increasing aluminum addition. Aluminum changed the morphology of tobermorite from plate-like to lath-like and fibrous. About a quarter of the (alumino)silicate chains in the C–S–H structure were linked though a Created by potrace 1.16, written by Peter Selinger 2001-2019 Si–O–Al Created by potrace 1.16, written by Peter Selinger 2001-2019 configuration, and this proportion was almost independent of aluminum addition. Furthermore, only Al[4] substituted for silicon in the aluminum incorporated C–S–H, while Al[6] just exited in the hydrogarnet phase. This work is beneficial for understanding the implication on micro-properties of by-products or admixtures containing aluminum in concrete.

The phase assembly and microstructure of the aluminum-incorporated CaO–SiO2–H2O system were investigated using XRD, SEM, FTIR and NMR depending on aluminum addition, reaction temperature and curing time.  相似文献   

10.
We fabricated amorphous InGaZnO thin film transistors (a-IGZO TFTs) with aluminum oxide (Al2O3) as a gate insulator grown through atomic layer deposition (ALD) method at different deposition temperatures (Tdep). The Al2O3 gate insulator with a low Tdep exhibited a high amount of hydrogen in the film, and the relationship between the hydrogen content and the electrical properties of the TFTs was investigated. The device with the Al2O3 gate insulator having a high H content showed much better transfer parameters and reliabilities than the low H sample. This is attributed to the defect passivation effect of H in the active layer, which is diffused from the Al2O3 layer. In addition, according to the post-annealing temperature (Tpost-ann), a-IGZO TFTs exhibited two unique changes of properties; the degradation in low Tpost-ann and the enhancement in high Tpost-ann, as explained in terms of H diffusion from the gate insulator to an active layer.

We fabricated amorphous InGaZnO thin film transistors (a-IGZO TFTs) with aluminum oxide (Al2O3) as a gate insulator grown through atomic layer deposition (ALD) method at different deposition temperatures (Tdep).  相似文献   

11.
To improve the reversible kinetics and electrochemical performance of a Nd–Mg–Ni-based alloy, NdMg11Ni + x wt% Ni (x = 100 or 200) samples were prepared through combining the addition of Ni element and ball-milling technology. Meanwhile, the effects of the addition of Ni element and the duration of milling on the NdMg11Ni samples were researched. The results indicate that the addition of Ni element has a beneficial effect on the dynamics of the samples. Meanwhile, the milling duration also has a beneficial effect on the high-rate discharging capabilities, the gaseous hydrogenation rate, and the dehydrogenation dynamics. When the ball-milling time is increased from 5 h to 60 h, the value of Rd20 (the ratio of the dehydrogenation capabilities within 20 min to the saturated hydrogenation capabilities) is raised from 62.20% to 71.59% for the x = 200 sample, and from 58.03% to 64.81% for the x = 100 sample; this is believed to be due to a decline in the activation energy resulting from an increase in the Ni content and ball-milling time. In addition, the Ea value of NdMg11Ni + 200 wt% Ni with a ball-milling time of 60 h is 55.7 kJ mol−1.

Both ball grinding and increasing the nickel content can effectively reduce the dehydrogenation activation energy of a RE–Mg-based alloy.  相似文献   

12.
13.
Nanoporous silver (NPS) was fabricated by dealloying Ag–Al alloy ribbons with nominal compositions of 30, 35 and 40 at% Ag (corresponding to hypoeutectic composition, eutectic composition and hypereutectic composition, respectively). The microstructures of the Ag–Al precursor and as-dealloyed samples were observed using a scanning electron microscope (SEM) and a transmission electron microscope (TEM) as well as via focused ion beam (FIB) technique. We concluded that with the increase in Ag content from 30 to 40 at%, the diameter of ligament increased from 70 ± 15 nm to 115 ± 35 nm. Due to the method of crystalline solidification and the distribution of α-Al(Ag) and γ-Ag2Al phases, the as-dealloyed Ag35Al65 alloy exhibited a homogeneous ligament/pore structure, whereas the microstructures of Ag30Al70 and Ag40Al60 showed thinner and coarser ligament structures, respectively.

Nanoporous silver (NPS) was fabricated by dealloying Ag–Al alloy ribbons with nominal compositions of 30, 35 and 40 at% Ag (corresponding to hypoeutectic composition, eutectic composition and hypereutectic composition, respectively).  相似文献   

14.
The effect of spontaneous alloying of non-stoichiometric aqueous Ag–In–S (AIS) and Cu–In–S (CIS) quantum dots (QDs) stabilized by surface glutathione (GSH) complexes was observed spectroscopically due to the phenomenon of band bowing typical for the solid–solution Cu(Ag)–In–S (CAIS) QDs. The alloying was found to occur even at room temperature and can be accelerated by a thermal treatment of colloidal mixtures at around 90 °C with no appreciable differences in the average size observed between alloyed and original individual QDs. An equilibrium between QDs and molecular and clustered metal–GSH complexes, which can serve as “building material” for the new mixed CAIS QDs, during the spontaneous alloying is assumed to be responsible for this behavior of GSH-capped ternary QDs. The alloying effect is expected to be of a general character for different In-based ternary chalcogenides.

The effect of spontaneous alloying of aqueous glutathione-capped Ag–In–S and Cu–In–S quantum dots (QDs) into quaternary Cu(Ag)–In–S QDs is reported.  相似文献   

15.
Tin (Sn) has a low melting temperature, i.e., 231.9 °C for the bulk, and the capability to form compounds with many metals. The galvanic reaction between Sn nanoparticles (NPs) as the core and silver nitrate at room temperature under argon gas in an organic solvent without any reducing power, was employed for the first time to coat an Ag–Sn intermetallic shell, i.e., Ag3Sn and/or Ag4Sn, on Sn NPs. For spherical Sn NPs, the NPs retained a spherical shape after coating. Uniform and Janus structures consisting of a β-Sn core with Ag–Sn shell were observed in the resulting NPs and their population related to the input molar ratios of the metal precursors. The observation of the intermetallic shell is general for both spherical and rod-shape Sn NPs. The formation of the intermetallic shell indicated that two reactions occurred sequentially, first reduction of Ag ions to Ag atoms by the Sn core, followed by interdiffusion of Ag and Sn to form the Ag–Sn intermetallic shell.

Coating of Ag–Sn intermetallic compound on Sn nanoparticles at room temperature.  相似文献   

16.
The epidemics of obesity and metabolic disorders have well-recognized health and economic burdens. Pharmacologic treatments for these diseases remain unsatisfactory with respect to both efficacy and side-effect profiles. Here, we have identified a potential central role for T-type calcium channels in regulating body weight maintenance and sleep. Previously, it was shown that mice lacking CaV3.1 T-type calcium channels have altered sleep/wake activity. We found that these mice were also resistant to high-fat diet–induced weight gain, without changes in food intake or sensitivity to high-fat diet–induced disruptions of diurnal rhythm. Administration of a potent and selective antagonist of T-type calcium channels, TTA-A2, to normal-weight animals prior to the inactive phase acutely increased sleep, decreased body core temperature, and prevented high-fat diet–induced weight gain. Administration of TTA-A2 to obese rodents reduced body weight and fat mass while concurrently increasing lean muscle mass. These effects likely result from better alignment of diurnal feeding patterns with daily changes in circadian physiology and potentially an increased metabolic rate during the active phase. Together, these studies reveal what we believe to be a previously unknown role for T-type calcium channels in the regulation of sleep and weight maintenance and suggest the potential for a novel therapeutic approach to treating obesity.  相似文献   

17.
We have described previously positive inotropy and increased levels of inositol-l-phosphate as in vitro responses to angiotensin II in cardiac tissue. In this study, changes in cardiac myocyte-free cytosolic calcium stimulated by angiotensin II were monitored with the fluorescent calcium indicator dye Fura-2. There was an initial peak transient increase followed by a sustained increase in cytosolic-free calcium in response to angiotensin II (10(-9)-10(-6) M). The peak transient response in cytosolic-free calcium after addition of angiotensin II (10(-7) M) occurred at 23 +/- 4 sec and was stimulated 2.16-fold (332 +/- 56 nM) above basal levels (154 +/- 14.7 nM). The calcium response was blocked or reversed by addition of verapamil (10(-8) M), lanthanum (0.2 mM) and zero calcium buffer. Angiotensin II receptor-mediated stimulation of inositol phosphates was quantified after separation by high-performance liquid chromatography in cultured chick heart cells prelabeled with L-myo-[1,2-3H(N)]inositol. A time course indicated that the peak response of the angiotensin II (10(-8) M)-stimulated increase in inositol-1,4,5-trisphosphate was at 30 sec. Angiotensin II (10(-8) M) significantly stimulated inositol-1,4-diphosphate (45%) and inositol-1,4,5-trisphosphate (78%) above basal levels. Bordetella pertussis toxin treatment of myocyte cultures in doses (500 ng/ml, 24 hr) shown to fully ADP-ribosylate a toxin-sensitive 41 KD alpha-subunit, blocked completely the angiotensin II-stimulated increases in inositol 1,4-diphosphate, inositol-1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. The rise in cytosolic-free calcium in response to angiotensin II was not blocked or inhibited by toxin pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

18.
We have performed the first-principles method to study the structural stability and helium diffusion behavior of Fe–Cr alloys. The calculated bulk modulus of 284.935 GPa in the non-magnetic (NM) state is in good agreement with others. We have obtained solid evidence that the alloy structures meet the mechanical stability criteria and lattice dynamics conditions in the anti-ferromagnetism (AFM) and non-magnetic (NM) states. Compared with bulk γ-Fe, a slightly larger Young''s modulus indicates that the doping of Cr helps to enhance the stiffness of the material and the ability to resist the reversible deformation of shear stress, but the ductility decreased slightly. Our results revealed that the addition of interstitial He atom promotes the expansion and deformation of the lattice, and further enlarges the cell volume. The presence of Cr in the alloy structures promotes the migration of a single helium atom between octahedral interstitials, and at the same time, inhibits the diffusion of helium atoms between tetrahedral interstitials to a large extent, which seem to be trapped in tetrahedral interstitials and cannot escape. The electronic properties show that the alloy materials exhibit obvious metallicity, and the doping of Cr generates an impurity state at lower energy, which is mainly formed by the s, p of Fe and s, p shell electrons of Cr. The charge density difference graphs corroborate that there is bonding interactions between Fe and Cr atoms. Bader charge analysis shows that a stronger polar covalent bond is formed between Fe and Cr in the non-magnetic (NM) state than in the anti-ferromagnetism (AFM) state. Our results provide useful information for understanding the initial growth of helium bubbles in experiments.

We have performed the first-principles method to study the structural stability and helium diffusion behavior of Fe–Cr alloys.  相似文献   

19.
20.
We investigate the thermal behaviour and physical properties of the crystals of the organic inorganic hybrid perovskite [(NH3)(CH2)4(NH3)]CuCl4. The compound''s thermal stability curve as per thermogravimetric analysis exhibits a stable state up to ∼495 K, while the weight loss observed near 538 K corresponds to partial thermal decomposition. The 1H nuclear magnetic resonance (NMR) chemical shifts for NH3 change more significantly with temperature than those for CH2, because the organic cation motion is enhanced at both ends of the organic chain. The 13C NMR chemical shifts for the ‘CH2-1’ units of the chain show an anomalous change, and those for ‘CH2-2’ (units closer to NH3) are shifted sharply. Additionally, the 14N NMR spectra reflect the changes of local symmetry near TC (=323 K). Moreover, the 13C T values for CH2-2 are smaller than those for CH2-1, and the 13C T data curve for CH2-1 exhibits an anomalous behaviour between 260 and 310 K. These smaller T values at lower temperatures indicate that 1H and 13C in the organic chains are more flexible at these temperatures. The NH3 group is attached to both ends of the organic chain, and NH3 forms a N–H⋯Cl hydrogen bond with the Cl ion of inorganic CuCl4. When H and C are located close to the paramagnetic Cu2+ ion, the T value is smaller than when these are located far from the paramagnetic ion.

We investigate the thermal behaviour and physical properties of the crystals of the organic inorganic hybrid perovskite [(NH3)(CH2)4(NH3)]CuCl4.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号