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1.
目的 探讨泽泻汤加味方对盐敏感性肾小球系膜细胞中AngII-NADPH-ROS信号通路的作用机制。方法 采用高盐和AngII诱导大鼠肾小球系膜细胞的方法建立盐敏感性高血压体外细胞模型,设正常组、模型组、阳性药缬沙坦组、泽泻汤加味方（高、中、低剂量）组。CKK-8法测定细胞活性;RT-qPCR方法检测细胞中Agtr1a、Cyba、NOX4的mRNA表达水平;Western blot方法检测细胞中AT1R、P22、P47、NOX4的蛋白质表达水平;活性氧检测试剂盒检测细胞中ROS水平。结果 与正常组比较,模型组细胞中Agtr1a、Cyba、NOX4的mRNA表达水平、AT1R、P22、P47、NOX4蛋白表达水平以及ROS表达水平显著升高（P<0.05）。与模型组比较,缬沙坦组及泽泻汤加味方中剂量组Agtr1a、Cyba、NOX4的mRNA表达水平、AT1R、P22、P47、NOX4蛋白表达水平以及ROS表达水平显著降低（P<0.05）。不同浓度泽泻汤加味方组间,中剂量组对AngII-NADPH-ROS信号通路的下调作用最为明显。结论 泽泻汤加味方对盐敏感性高血压肾损害的保护作用可能与抑制AngII-NADPH-ROS信号通路有关。 相似文献
2.
Glutamate receptor-like genes form Ca2+ channels in pollen tubes and are regulated by pistil D-serine 总被引：1，自引：0，他引：1
Michard E Lima PT Borges F Silva AC Portes MT Carvalho JE Gilliham M Liu LH Obermeyer G Feijó JA 《Science (New York, N.Y.)》2011,332(6028):434-437
Elevations in cytosolic free calcium concentration ([Ca(2+)](cyt)) constitute a fundamental signal transduction mechanism in eukaryotic cells, but the molecular identity of Ca(2+) channels initiating this signal in plants is still under debate. Here, we show by pharmacology and loss-of-function mutants that in tobacco and Arabidopsis, glutamate receptor-like channels (GLRs) facilitate Ca(2+) influx across the plasma membrane, modulate apical [Ca(2+)](cyt) gradient, and consequently affect pollen tube growth and morphogenesis. Additionally, wild-type pollen tubes grown in pistils of knock-out mutants for serine-racemase (SR1) displayed growth defects consistent with a decrease in GLR activity. Our findings reveal a novel plant signaling mechanism between male gametophyte and pistil tissue similar to amino acid-mediated communication commonly observed in animal nervous systems. 相似文献
3.
Ca(2+)-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose 总被引：19，自引：0，他引：19
Calcium-induced calcium release (CICR) may function widely in calcium-mediated cell signaling, but has been most thoroughly characterized in muscle cells. In a homogenate of sea urchin eggs, which display transients in the intracellular free calcium concentration ([Ca2+]i) during fertilization and anaphase, addition of Ca2+ triggered CICR. Ca2+ release was also induced by the CICR modulators ryanodine and caffeine. Responses to both Ca2+ and CICR modulators (but not Ca2+ release mediated by inositol 1,4,5-trisphosphate) were inhibited by procaine and ruthenium red, inhibitors of CICR. Intact eggs also displayed transients of [Ca2+]i when microinjected with ryanodine. Cyclic ADP-ribose, a metabolite with potent Ca(2+)-releasing properties, appears to act by way of the CICR mechanism and may thus be an endogenous modulator of CICR. A CICR mechanism is present in these nonmuscle cells as is assumed in various models of intracellular Ca2+ wave propagation. 相似文献
4.
Giorgi C Ito K Lin HK Santangelo C Wieckowski MR Lebiedzinska M Bononi A Bonora M Duszynski J Bernardi R Rizzuto R Tacchetti C Pinton P Pandolfi PP 《Science (New York, N.Y.)》2010,330(6008):1247-1251
The promyelocytic leukemia (PML) tumor suppressor is a pleiotropic modulator of apoptosis. However, the molecular basis for such a diverse proapoptotic role is currently unknown. We show that extranuclear Pml was specifically enriched at the endoplasmic reticulum (ER) and at the mitochondria-associated membranes, signaling domains involved in ER-to-mitochondria calcium ion (Ca(2+)) transport and in induction of apoptosis. We found Pml in complexes of large molecular size with the inositol 1,4,5-trisphosphate receptor (IP(3)R), protein kinase Akt, and protein phosphatase 2a (PP2a). Pml was essential for Akt- and PP2a-dependent modulation of IP(3)R phosphorylation and in turn for IP(3)R-mediated Ca(2+) release from ER. Our findings provide a mechanistic explanation for the pleiotropic role of Pml in apoptosis and identify a pharmacological target for the modulation of Ca(2+) signals. 相似文献
5.
Sonkusare SK Bonev AD Ledoux J Liedtke W Kotlikoff MI Heppner TJ Hill-Eubanks DC Nelson MT 《Science (New York, N.Y.)》2012,336(6081):597-601
Major features of the transcellular signaling mechanism responsible for endothelium-dependent regulation of vascular smooth muscle tone are unresolved. We identified local calcium (Ca(2+)) signals ("sparklets") in the vascular endothelium of resistance arteries that represent Ca(2+) influx through single TRPV4 cation channels. Gating of individual TRPV4 channels within a four-channel cluster was cooperative, with activation of as few as three channels per cell causing maximal dilation through activation of endothelial cell intermediate (IK)- and small (SK)-conductance, Ca(2+)-sensitive potassium (K(+)) channels. Endothelial-dependent muscarinic receptor signaling also acted largely through TRPV4 sparklet-mediated stimulation of IK and SK channels to promote vasodilation. These results support the concept that Ca(2+) influx through single TRPV4 channels is leveraged by the amplifier effect of cooperative channel gating and the high Ca(2+) sensitivity of IK and SK channels to cause vasodilation. 相似文献
6.
《Science (New York, N.Y.)》1994,266(5184):353
In the response by E. A. Finch and S. M. Goldin (5 Aug., p. 813) to the technical comment "Calcium and inositol 1,4,5-trisphosphate-induced Ca(2+) release" by L. Combettes and P. Champeil (5 Aug., p. 813), in parts B and C of figure 1 (p. 814), the insets referring to Ca concentrations were inadvertantly interchanged. The concentration for figure 1B should have been, "300 nM Ca" and that for figure 1C should have been, "10 nM Ca." 相似文献
7.
Zhao Y Araki S Wu J Teramoto T Chang YF Nakano M Abdelfattah AS Fujiwara M Ishihara T Nagai T Campbell RE 《Science (New York, N.Y.)》2011,333(6051):1888-1891
Engineered fluorescent protein (FP) chimeras that modulate their fluorescence in response to changes in calcium ion (Ca(2+)) concentration are powerful tools for visualizing intracellular signaling activity. However, despite a decade of availability, the palette of single FP-based Ca(2+) indicators has remained limited to a single green hue. We have expanded this palette by developing blue, improved green, and red intensiometric indicators, as well as an emission ratiometric indicator with an 11,000% ratio change. This series enables improved single-color Ca(2+) imaging in neurons and transgenic Caenorhabditis elegans. In HeLa cells, Ca(2+) was imaged in three subcellular compartments, and, in conjunction with a cyan FP-yellow FP-based indicator, Ca(2+) and adenosine 5'-triphosphate were simultaneously imaged. This palette of indicators paints the way to a colorful new era of Ca(2+) imaging. 相似文献
8.
Localized all-or-none calcium liberation by inositol trisphosphate 总被引：14，自引：0，他引：14
Laser confocal microscopy was used to monitor calcium ion (Ca2+) liberation from highly localized (micrometer) regions of intact Xenopus oocytes in response to photo-released inositol 1,4,5-trisphosphate (InsP3). Local Ca2+ release varied in an all-or-none manner with increasing amount of InsP3, in contrast to signals recorded from larger areas, which grew progressively as the concentration of InsP3 was raised above a threshold. Liberation of Ca2+ was restricted to within a few microns of the site of InsP3 release and, in response to agonist activation, localized regions of the oocyte showed asynchronous oscillations in cytoplasmic Ca2+ release. Results obtained with this technique provided direct evidence that InsP3-induced Ca2+ liberation was quantized and suggest that the InsP3-sensitive Ca2+ pool may be a collection of independent, localized compartments that release Ca2+ in an all-or-none manner. 相似文献
9.
Sodium/calcium (Na(+)/Ca(2+)) exchangers (NCX) are membrane transporters that play an essential role in maintaining the homeostasis of cytosolic Ca(2+) for cell signaling. We demonstrated the Na(+)/Ca(2+)-exchange function of an NCX from Methanococcus jannaschii (NCX_Mj) and report its 1.9 angstrom crystal structure in an outward-facing conformation. Containing 10 transmembrane helices, the two halves of NCX_Mj share a similar structure with opposite orientation. Four ion-binding sites cluster at the center of the protein: one specific for Ca(2+) and three that likely bind Na(+). Two passageways allow for Na(+) and Ca(2+) access to the central ion-binding sites from the extracellular side. Based on the symmetry of NCX_Mj and its ability to catalyze bidirectional ion-exchange reactions, we propose a structure model for the inward-facing NCX_Mj. 相似文献
10.
Liu KS Siebert M Mertel S Knoche E Wegener S Wichmann C Matkovic T Muhammad K Depner H Mettke C Bückers J Hell SW Müller M Davis GW Schmitz D Sigrist SJ 《Science (New York, N.Y.)》2011,334(6062):1565-1569
The molecular machinery mediating the fusion of synaptic vesicles (SVs) at presynaptic active zone (AZ) membranes has been studied in detail, and several essential components have been identified. AZ-associated protein scaffolds are viewed as only modulatory for transmission. We discovered that Drosophila Rab3-interacting molecule (RIM)-binding protein (DRBP) is essential not only for the integrity of the AZ scaffold but also for exocytotic neurotransmitter release. Two-color stimulated emission depletion microscopy showed that DRBP surrounds the central Ca(2+) channel field. In drbp mutants, Ca(2+) channel clustering and Ca(2+) influx were impaired, and synaptic release probability was drastically reduced. Our data identify RBP family proteins as prime effectors of the AZ scaffold that are essential for the coupling of SVs, Ca(2+) channels, and the SV fusion machinery. 相似文献
11.
Astrocytes play active roles in brain physiology. They respond to neurotransmitters and modulate neuronal excitability and synaptic function. However, the influence of astrocytes on synaptic transmission and plasticity at the single synapse level is unknown. Ca(2+) elevation in astrocytes transiently increased the probability of transmitter release at hippocampal area CA3-CA1 synapses, without affecting the amplitude of synaptic events. This form of short-term plasticity was due to the release of glutamate from astrocytes, a process that depended on Ca(2+) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein and that activated metabotropic glutamate receptors (mGluRs). The transient potentiation of transmitter release became persistent when the astrocytic signal was temporally coincident with postsynaptic depolarization. This persistent plasticity was mGluR-mediated but N-methyl-d-aspartate receptor-independent. These results indicate that astrocytes are actively involved in the transfer and storage of synaptic information. 相似文献
12.
Voltage-independent calcium release in heart muscle 总被引：21，自引：0，他引：21
The Ca2+ that activates contraction in heart muscle is regulated as in skeletal muscle by processes that depend on voltage and intracellular Ca2+ and involve a positive feedback system. How the initial electrical signal is amplified in heart muscle has remained controversial, however. Analogous protein structures from skeletal muscle and heart muscle have been identified physiologically and sequenced; these include the Ca2+ channel of the sarcolemma and the Ca2+ release channel of the sarcoplasmic reticulum. Although the parallels found in cardiac and skeletal muscles have provoked valuable experiments in both tissues, separation of the effects of voltage and intracellular Ca2+ on sarcoplasmic reticulum Ca2+ release in heart muscle has been imperfect. With the use of caged Ca2+ and flash photolysis in voltage-clamped heart myocytes, effects of membrane potential in heart muscle cells on Ca2+ release from intracellular stores have been studied. Unlike the response in skeletal muscle, voltage across the sarcolemma of heart muscle does not affect the release of Ca2+ from the sarcoplasmic reticulum, suggesting that other regulatory processes are needed to control Ca2(+)-induced Ca2+ release. 相似文献
13.
Scorrano L Oakes SA Opferman JT Cheng EH Sorcinelli MD Pozzan T Korsmeyer SJ 《Science (New York, N.Y.)》2003,300(5616):135-139
BAX and BAK are "multidomain" proapoptotic proteins that initiate mitochondrial dysfunction but also localize to the endoplasmic reticulum (ER). Mouse embryonic fibroblasts deficient for BAX and BAK (DKO cells) were found to have a reduced resting concentration of calcium in the ER ([Ca2+]er) that results in decreased uptake of Ca2+ by mitochondria after Ca2+ release from the ER. Expression of SERCA (sarcoplasmic-endoplasmic reticulum Ca2+ adenosine triphosphatase) corrected [Ca2+]er and mitochondrial Ca2+ uptake in DKO cells, restoring apoptotic death in response to agents that release Ca2+ from intracellular stores (such as arachidonic acid, C2-ceramide, and oxidative stress). In contrast, targeting of BAX to mitochondria selectively restored apoptosis to "BH3-only" signals. A third set of stimuli, including many intrinsic signals, required both ER-released Ca2+ and the presence of mitochondrial BAX or BAK to fully restore apoptosis. Thus, BAX and BAK operate in both the ER and mitochondria as an essential gateway for selected apoptotic signals. 相似文献
14.
The molecular pathways involved in retrograde signal transduction at synapses and the function of retrograde communication are poorly understood. Here, we demonstrate that postsynaptic calcium 2+ ion (Ca2+) influx through glutamate receptors and subsequent postsynaptic vesicle fusion trigger a robust induction of presynaptic miniature release after high-frequency stimulation at Drosophila neuromuscular junctions. An isoform of the synaptotagmin family, synaptotagmin 4 (Syt 4), serves as a postsynaptic Ca2+ sensor to release retrograde signals that stimulate enhanced presynaptic function through activation of the cyclic adenosine monophosphate (cAMP)-cAMP-dependent protein kinase pathway. Postsynaptic Ca2+ influx also stimulates local synaptic differentiation and growth through Syt 4-mediated retrograde signals in a synapse-specific manner. 相似文献
15.
不同缓释肥用量对莴笋品质的效应 总被引：1，自引：0，他引：1
通过盆栽试验研究了不同缓释肥（SR）用量对莴笋产量和品质的效应。结果表明：不同施肥处理间莴笋产量有极显著差异。不同缓释肥用量处理提高莴笋产量32．3％～59．9％,以SR（M）〉SR（L）〉SR（H）,莴笋产量与缓释肥用量间存在二次回归关系（Y＝-10．7 x^2＋60．62x＋11．2R^2—0．9872）,缓释肥的增产效率以SR（L）〉SR（M）〉SR（H）．不同缓释肥用量处理提高莴笋叶绿素a、叶绿素a＋b含量和叶绿素a／b达38．9％～88．9％和20．5％～58．9％和6．3％～40．7％,增加莴笋叶绿素b含量28．7％～33．3％（SR（M）处理除外）。除SR（L）处理使莴笋可溶性糖含量降低32．7％外,不同缓释肥用量处理提高莴笋硝酸盐、Vc、可溶性糖和氨基酸含量达10．3％～27．0％,40．9％～151．7％,11．5％～19．2％和0．4％～61．1％。结合产量和品质来看,缓释肥用量处理中SR（M）是莴笋获得高产优质的最佳处理。 相似文献
16.
Intracellular calcium (Ca2+) is a ubiquitous second messenger. Information is encoded in the magnitude, frequency, and spatial organization of changes in the concentration of cytosolic free Ca2+. Regenerative spiral waves of release of free Ca2+ were observed by confocal microscopy in Xenopus laevis oocytes expressing muscarinic acetylcholine receptor subtypes. This pattern of Ca2+ activity is characteristic of an intracellular milieu that behaves as a regenerative excitable medium. The minimal critical radius for propagation of focal Ca2+ waves (10.4 micrometers) and the effective diffusion constant for the excitation signal (2.3 x 10(-6) square centimeters per second) were estimated from measurements of velocity and curvature of circular wavefronts expanding from foci. By modeling Ca2+ release with cellular automata, the absolute refractory period for Ca2+ stores (4.7 seconds) was determined. Other phenomena expected of an excitable medium, such as wave propagation of undiminished amplitude and annihilation of colliding wavefronts, were observed. 相似文献
17.
In neurons, individual dendritic spines isolate N-methyl-d-aspartate (NMDA) receptor-mediated calcium ion (Ca2+) accumulations from the dendrite and other spines. However, the extent to which spines compartmentalize signaling events downstream of Ca2+ influx is not known. We combined two-photon fluorescence lifetime imaging with two-photon glutamate uncaging to image the activity of the small guanosine triphosphatase Ras after NMDA receptor activation at individual spines. Induction of long-term potentiation (LTP) triggered robust Ca2+-dependent Ras activation in single spines that decayed in approximately 5 minutes. Ras activity spread over approximately 10 micrometers of dendrite and invaded neighboring spines by diffusion. The spread of Ras-dependent signaling was necessary for the local regulation of the threshold for LTP induction. Thus, Ca2+-dependent synaptic signals can spread to couple multiple synapses on short stretches of dendrite. 相似文献
18.
Launay P Cheng H Srivatsan S Penner R Fleig A Kinet JP 《Science (New York, N.Y.)》2004,306(5700):1374-1377
TRPM4 has recently been described as a calcium-activated nonselective (CAN) cation channel that mediates membrane depolarization. However, the functional importance of TRPM4 in the context of calcium (Ca2+) signaling and its effect on cellular responses are not known. Here, the molecular inhibition of endogenous TRPM4 in T cells was shown to suppress TRPM4 currents, with a profound influence on receptor-mediated Ca2+ mobilization. Agonist-mediated oscillations in intracellular Ca2+ concentration ([Ca2+]i), which are driven by store-operated Ca2+ influx, were transformed into a sustained elevation in [Ca2+]i. This increase in Ca2+ influx enhanced interleukin-2 production. Thus, TRPM4-mediated depolarization modulates Ca2+ oscillations, with downstream effects on cytokine production in T lymphocytes. 相似文献
19.
种子是农业生产中最基本的生产资料。种子成功整齐发芽是作物生长发育、高产稳产的第1步。活性氧(ROS)是一类多功能化合物,在种子萌发过程中发挥着关键作用。本研究介绍了ROS的种类、产生部位以及对种子萌发的“氧化窗口”效应,总结了ROS调控种子萌发的机制并对未来研究提出展望。目前ROS调控种子萌发的研究集中于：(1)当条件合适时,ROS维持在一个适当的水平,启动赤霉素(GA)等信号转导途径、抑制脱落酸(ABA)途径,调控细胞膨大,促进种子萌发;(2)当面临不利环境时,ROS的过量积累会对生物大分子造成氧化损伤,诱导ABA途径,抑制种子萌发。ROS通过生物分子氧化、种皮弱化和胚乳衰退解除种子休眠。今后,需进一步探索对种子萌发起到积极作用的“氧化窗口”范围,同时结合转录组学和代谢组学技术筛选种子萌发中调控ROS含量相关基因,更好地了解ROS促进种子萌发的机制。图3表1参94 相似文献
20.
《Science (New York, N.Y.)》1992,258(5080):205
Figure 3 on page 253 of the report "Block of Ca(2+) wave and Ca(2+) oscillation by antibody to the inositol 1,4,5-trisphosphate receptor in fertilized hamster eggs" by Si. Miyazaki et al. (10 July, p. 251) was printed so that the sperm drawn on the computer display were not visible. Also, the scale bar for (F), which was 50 microm, was not clear. The correct figure is reproduced below. [See figure in the PDF file]. 相似文献