共查询到20条相似文献,搜索用时 31 毫秒
1.
Chen Zhang Yun Huang Yusheng Jiang Nagaraju Mulpuri Ling Wei Donald Hamelberg Edward M. Brown Jenny J. Yang 《The Journal of biological chemistry》2014,289(8):5296-5309
Functional positive cooperative activation of the extracellular calcium ([Ca2+]o)-sensing receptor (CaSR), a member of the family C G protein-coupled receptors, by [Ca2+]o or amino acids elicits intracellular Ca2+ ([Ca2+]i) oscillations. Here, we report the central role of predicted Ca2+-binding site 1 within the hinge region of the extracellular domain (ECD) of CaSR and its interaction with other Ca2+-binding sites within the ECD in tuning functional positive homotropic cooperativity caused by changes in [Ca2+]o. Next, we identify an adjacent l-Phe-binding pocket that is responsible for positive heterotropic cooperativity between [Ca2+]o and l-Phe in eliciting CaSR-mediated [Ca2+]i oscillations. The heterocommunication between Ca2+ and an amino acid globally enhances functional positive homotropic cooperative activation of CaSR in response to [Ca2+]o signaling by positively impacting multiple [Ca2+]o-binding sites within the ECD. Elucidation of the underlying mechanism provides important insights into the longstanding question of how the receptor transduces signals initiated by [Ca2+]o and amino acids into intracellular signaling events. 相似文献
2.
C. Sandler K. Kirschfeld 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1991,169(3):299-311
Summary Ion-selective microelectrodes inserted into the compound eyes of Calliphora were used to monitor the changes in extracellular concentration of Ca2+ and Na+ (Cao, Nao) brought about by a 1-min exposure to white light (maximal luminous intensity 0.1 cd/cm2).Using Ringer solution as the reference (Ca2+ = 1 mM), the dark concentration of the calcium in the retina was found to be (1.4 ± 0.4) mM (n=12). Stimulation with light reduces Cao. At intensities near maximal the Cao signal is phasic, reaching a transient minimum about 6 s after light onset
and then rising to a nearly stable plateau below the dark level (-3.3% ± 2.6%). Cao signals measured in the white-eyed mutant (chalky), which lacks pigment granules, are comparable to those in the wild type.Conclusions: (a) There are no extracellular Ca2+ binding sites that regulate light adaptation, such as were postulated by Hochstrate and Hamdorf (1985). (b) Ca2+ influx into the photoreceptors seems to be necessary for light adaptation, (c) The pigment granules have no major function in intracellular calcium regulation.The time course of the Nao signals resembles that of the Cao signals. Because the percentage concentration change is small, light-induced extracellular Na+-depletion cannot contribute to a reduced response amplitude at light adaptation.Abbreviations
Ca
i
intracellular Ca2+ concentration
-
Ca
o
extracellular Ca2+ concentration
-
Kino
extracellular K+ concentration
-
Na
o
extracellular Na+ concentration 相似文献
3.
Yan-Lei Fu Guo-Bin Zhang Xin-Fang Lv Yuan Guan Hong-Ying Yi Ji-Ming Gong 《The Plant cell》2013,25(8):2878-2891
Elevations in extracellular calcium ([Ca2+]o) are known to stimulate cytosolic calcium ([Ca2+]cyt) oscillations to close stomata. However, the underlying mechanisms regulating this process remain largely to be determined. Here, through the functional characterization of the calcium underaccumulation mutant cau1, we report that the epigenetic regulation of CAS, a putative Ca2+ binding protein proposed to be an external Ca2+ sensor, is involved in this process. cau1 mutant plants display increased drought tolerance and stomatal closure. A mutation in CAU1 significantly increased the expression level of the calcium signaling gene CAS, and functional disruption of CAS abolished the enhanced drought tolerance and stomatal [Ca2+]o signaling in cau1. Map-based cloning revealed that CAU1 encodes the H4R3sme2 (for histone H4 Arg 3 with symmetric dimethylation)-type histone methylase protein arginine methytransferase5/Shk1 binding protein1. Chromatin immunoprecipitation assays showed that CAU1 binds to the CAS promoter and modulates the H4R3sme2-type histone methylation of the CAS chromatin. When exposed to elevated [Ca2+]o, the protein levels of CAU1 decreased and less CAU1 bound to the CAS promoter. In addition, the methylation level of H4R3sme2 decreased in the CAS chromatin. Together, these data suggest that in response to increases in [Ca2+]o, fewer CAU1 protein molecules bind to the CAS promoter, leading to decreased H4R3sme2 methylation and consequent derepression of the expression of CAS to mediate stomatal closure and drought tolerance. 相似文献
4.
The roles of Ca2+ mobilization in development of tension induced by acetylcholine (ACh, 0.1–100 µM) in swine tracheal smooth muscle strips were studied. Under control conditions, ACh induced a transient increase in free cytosolic calcium concentration ([Ca2+]i) that declined to a steady-state level. The peak increase in [Ca2+]i correlated with the magnitude of tension at each [ACh] after a single exposure to ACh, while the steady-state [Ca2+]i did not. Removal of extracellular Ca2+ had little effect on peak [Ca2+]i but greatly reduced steady-state increases in [Ca2+]i and tension. Verapamil inhibited steady-state [Ca2+]i only at [ACh]<1 µM. After depletion of internal Ca2+ stores by 10 min exposure to ACh in Ca2+-free solution and then washout of ACh for 5 min in Ca2+-free solution, simultaneous re-exposure to ACh in the presence of 2.5 mM Ca2+ increased [Ca2+]i to the control steady-state level without overshoot. The tension attained was the same as control for each [ACh] used. Continuous exposure to successively increasing [ACh] (0.1–100 µM) also reduced the overshoot of [Ca2+]i at 10 and 100 µM ACh, yet tension reached control levels at each [ACh] used. We conclude that the steady-state increase in [Ca2+]i is necessary for tension maintenance and is dependent on Ca2+ influx through voltage-gated calcium channels at 0.1 µM ACh and through a verapamil-insensitive pathway at 10 and 100 µM. The initial transient increase in calcium arises from intracellular stores and is correlated with the magnitude of tension only in muscles that have completely recovered from previous exposure to agonists. 相似文献
5.
A surprising effect is the direct action of Ca(2+) on redox reactions of ortho-quinoid compounds. The effect of Ca(2+) on oxidation of the sea urchin pigment 6-ethyl-2,3,5,7,8-pentahydroxy-1,4-naphthoquinone (echinochrome A) has been studied by electron paramagnetic resonance (EPR) spectroscopy, by UV/VIS absorbance spectroscopy, and by measurement of oxygen consumption. Echinochrome A per se reacted with dioxygen only in an alkaline solution; 2,3-semiquinone anion-radical of echinochrome A and superoxide anion-radical were the intermediates of the oxidation. Addition of calcium ions sharply increased the rate of echinochrome A autooxidation at alkaline pH and provoked oxidation at neutral pH. To explain this phenomenon we have focused on changes of the acid-base properties of echinochrome A in the presence of calcium and on stabilization of 2,3-semiquinone anion-radical of echinochrome A by Ca(2+). Dissociation constants (pK(a1), pK(a2), and pK(a3)) of echinochrome A determined by potentiometric titration were 5.20, 6.78, and >10 in calcium-free solution and 5.00, 6.10, and 7.15 in the presence of Ca(2+). We have found that Ca(2+) forms an insoluble adduct with the 2,3-semiquinone anion-radical. Thus, the effect of redox-inert calcium on the free radical reactions could be explained (i) by additional deprotonation of echinochrome A and (ii) by formation of a Ca(2+)-naphtho-2,3-semiquinone complex (calcium semiquinonate). Additionally, we have shown that the dried red spines from Strongylocentrotus intermedius possess paramagnetic properties; the EPR signal of the natural spines was similar to that of calcium semiquinonate obtained in our artificial chemical system. 相似文献
6.
Modulation of the sinus rate and contractile force by taurine at different extracellular Ca2+ concentrations ([Ca2+]o) was examined using rat right atria loaded with forced swimming stress. Serum concentration of corticosterone profoundly
increased in stress-loaded rats as compared with native rats. The taurine level in serum also increased in stress-loaded rats,
but was not changed in the different heart tissues and aorta. Heat-shock protein (HSP72) was detectable in cardiac muscles
and in the lumen of cardiac blood vessels of stress-loaded rats using a monoclonal antibody. Increasing [Ca2+]o (from 0.9 to 3.6 mM) enhanced the sinus rate and contractile force in a [Ca2+]o-dependent fashion in native rats, but not in stress-loaded rats. Taurine (1–20 mM) caused a negative chronotropic and inotropic effect in a concentration-dependent manner. At 1.8 mM [Ca2+]o, the negative chronotropic effect of taurine (10–20 mM) was attenuated in stress-loaded rats as compared with native rats. These results indicate that swimming stress causes a
release of taurine into the serum and reduces the sensitivity to [Ca2+]o. Taurine administration might, in part, exhibit the protective actions on acute stress-induced responses. 相似文献
7.
Andreas Ziegler Bernd Walz 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1989,165(5):697-709
Summary Superfused slices of drone retina were used for a quantitative analysis of light-induced changes in extracellular Ca2+ concentration ([Ca2+]o) and extracellular space (ECS) volume. 20-ms light flashes elicited biphasic changes in [Ca2+]o. For a saturating flash a brief, initial decrease was followed by a transient increase of 120±34 M. Long, dim steps of light (5 min) produced either a decrease or an increase in [Ca2+]o depending strongly on the previous illumination. Brighter continuous lights caused the [Ca2+]o to increase transiently by 1.4 mM to a peak from which it decayed to a plateau, up to 0.6 mM above the dark concentration.Light flashes (20 ms) caused a shrinkage in ECS volume not exceeding 4%. Thus, changes in [Ca2+]o were almost completely due to Ca2+ fluxes between the ECS and adjacent cells. Continuous lights caused a shrinkage in ECS volume rarely exceeding 16%–20%. Thus, less than 15% of the measured Ca2+ changes could be attributed to shrinkage of the ECS. These data confirm that the ECS functions as a source and a sink for Ca2+ mobilized by light. For comparison, we also made a few measurements of changes in [Ca2+]o in the retina ofCalliphora.Abbreviations [Ca
2+]i
intracellular free Ca2+ concentration
- [Ca
2+]o
extracellular free Ca2+ concentration
-
ECS
extracellular space
-
ER
endoplasmic reticulum
-
TMA
+
tetramethylammonium ion 相似文献
8.
W. Z. Yang J. J. Fu L. Y. Yang X. Zhang Y. L. Zheng F. Feng Y. F. Xu 《Russian Journal of Plant Physiology》2014,61(6):818-827
Low-light (LL) intensity is a primary abiotic stressor that negatively influences turf grass quality. In the present experiment, we studied the effect of exogenous Ca2+ (0, 10, 50, 100, and 200 mM) on the antioxidant system, the accumulation of MDA and proline, the content of photosynthetic pigments in plant leaves in order to investigate whether exogenous Ca2+ treatment improves LL tolerance in tall fescue (Festuca arundinacea Schreb.). We have found that LL significantly reduced a number of growth parameters (plant height, leaf width, leaf fresh weight, root fresh weight, leaf dry weight, and root dry weight), chlorophyll (Chl) a and Chl b contents, and carotenoid (Car) levels, while considerably enhancing electrolyte leakage (EL), MDA accumulation, calcium (Ca2+) concentration, and generation of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2) and superoxide radical (O 2 ·? ). Moreover, LL significantly induced the activities of antioxidant enzymes, such as peroxidase (POD) and catalase (CAT), and slightly increased the activity of superoxide dismutase (SOD) in tall fescue leaves. In contrast, POD and SOD activities declined considerably while CAT activity significantly increased in plant roots under LL stress. The application of 50 mM Ca2+ significantly improved the aforementioned growth parameters, the content of photosynthetic pigments, and further enhanced the activities of POD, SOD, and CAT, but decreased electrolyte leakage and MDA and H2O2 levels in the leaves and roots of tall fescue under LL stress. These results suggest that Ca2+ is likely involved in a resistance to LL by regulating antioxidant enzyme action in tall fescue leaves and roots. 相似文献
9.
Abstract: The ability of various stimuli to convert Ca2+/calmodulin-dependent protein kinase II (CaMKII) into a Ca2+-independent (autonomous) form was examined in cultured embryonic rat hippocampal pyramidal neurons. The most effective stimulation by far was observed when cells were equilibrated in buffer containing low extracellular [Ca2+] ([Ca2+]o) (~50 nM) and then shifted to normal [Ca2+]o (~1.26 mM) by addition of CaCl2 (referred to as “Ca2+ stimulation”). Virtually complete (>90%) conversion of the kinase to the autonomous form occurred within 30–50 s, with a return to baseline within 5 min. By contrast, depolarization of cells with high [K+] or treatment with glutamate or a Ca2+ ionophore caused insignificant increases (<10%) in levels of the autonomous form. The Ca2+-stimulated increase in CaMKII autonomy coincided with a two- to threefold increase in kinase subunit phosphorylation. In the first 40 s of Ca2+ stimulation, 32P incorporation into the immunoprecipitated subunits of CaMKII occurred exclusively on threonine residues, including Thr286Thr287 of the α/β subunits. Longer incubation of cells resulted in a decline of phosphothreonine content, whereas levels of phosphoserine-containing peptides showed a significant increase. The activation of CaMKII by Ca2+ stimulation was accompanied by only a small rise in intracellular [Ca2+]. Inhibitor studies showed that Na+-dependent action potentials and Ca2+ influx through glutamate receptors or voltage-sensitive Ca2+ channels did not contribute to the activation. Moreover, CaMKII was not activated by extracellular addition of other cations, including Mn2+, Mg2+, Co2+, or Gd3+. Although the mechanism of Ca2+ stimulation is presently unclear, it may involve either activation of extracellular calcium receptors or capacitative calcium entry. The dramatic rise in CaMKII autonomy and the Ca2+ selectivity of the response suggest a direct and specific relationship between [Ca2+]o and the state of activation of the kinase in intact neurons. 相似文献
10.
In Arabidopsis, extracellular calcium (Ca2+o) promotes intracellular calcium (Ca2+i) transients and stomatal closure, which has been found to be regulated by the calcium sensing receptor (CAS). However, the detailed pathways for transducting the Ca2+o signal by CAS are still unclear. We found that nitric oxide (NO) and the hydrogen peroxide (H2O2) accumulated in the guard cell chloroplast were the two elements that act downstream of the CAS signaling and trigger the stomatal closure by prolonging Ca2+i transients.1 Here we provide more commentary on CAS-regulated H2O2 generation from chloroplast and Ca2+i transients in response to Ca2+o, as well as other potential mechanisms that may be involved in the CAS signaling pathway. 相似文献
11.
To elucidate the mechnism by which quercetin enhances the rate of tension development in skinned muscle fibers, effects on calcium release from longitudinal tubule-derived SR (LSR) after phosphate-supported calcium uptake were examined. In all studies, 100 μM quercetin (which inhibits initial calcium uptake velocity 85%) was added at or shortly after the time calcium content reached a maximum at various extravesicular Ca2+ concentrations (Cao). At moderate Cao (0.2–1.0 μM). where spontaneous calcium release rate depended on Cao, quercetin caused a marked stimulation of calcium release. This was accompanied by a 60% reduction in calcium influx and a 30-fold increase in calcium efflux. Thus, the previously reported quercetin-induced increase in the rate of tension development by skinned muscle fibers may result, at least in part, from sensitization of Ca2+-triggered calcium release to lower Cao. 相似文献
12.
Yusheng Jiang Yun Huang Hing-Cheung Wong Yubin Zhou Xue Wang Jun Yang Randy A. Hall Edward M. Brown Jenny J. Yang 《The Journal of biological chemistry》2010,285(43):33463-33474
Metabotropic glutamate receptor 1α (mGluR1α) exerts important effects on numerous neurological processes. Although mGluR1α is known to respond to extracellular Ca2+ ([Ca2+]o) and the crystal structures of the extracellular domains (ECDs) of several mGluRs have been determined, the calcium-binding site(s) and structural determinants of Ca2+-modulated signaling in the Glu receptor family remain elusive. Here, we identify a novel Ca2+-binding site in the mGluR1α ECD using a recently developed computational algorithm. This predicted site (comprising Asp-318, Glu-325, and Asp-322 and the carboxylate side chain of the receptor agonist, Glu) is situated in the hinge region in the ECD of mGluR1α adjacent to the reported Glu-binding site, with Asp-318 involved in both Glu and calcium binding. Mutagenesis studies indicated that binding of Glu and Ca2+ to their distinct but partially overlapping binding sites synergistically modulated mGluR1α activation of intracellular Ca2+ ([Ca2+]i) signaling. Mutating the Glu-binding site completely abolished Glu signaling while leaving its Ca2+-sensing capability largely intact. Mutating the predicted Ca2+-binding residues abolished or significantly reduced the sensitivity of mGluR1α not only to [Ca2+]o and [Gd3+]o but also, in some cases, to Glu. The dual activation of mGluR1α by [Ca2+]o and Glu has important implications for the activation of other mGluR subtypes and related receptors. It also opens up new avenues for developing allosteric modulators of mGluR function that target specific human diseases. 相似文献
13.
14.
Sarah L. Davies 《生物化学与生物物理学报:生物膜》2008,1778(10):2318-2324
The calcium-sensing receptor (CaR) is expressed on intestinal epithelial serosal membrane and in Caco-2 cells. In renal epithelium, CaR expressed on the basolateral membrane acts to limit excess tubular Ca2+ reabsorption. Therefore, here we investigated whether extracellular calcium (Cao2+) can regulate active or passive 45Ca2+ transport across differentiated Caco-2 monolayers via CaR-dependent or CaR-independent mechanisms. Raising the Cao2+ concentration from 0.8 to 1.6 mM increased transepithelial electrical resistance (TER) and decreased passive Ca2+ permeability but failed to alter active Ca2+ transport. The Cao2+ effect on TER was rapid, sustained and concentration-dependent. Increasing basolateral Mg2+ concentration increased TER and inhibited both passive and active Ca2+ transport, whereas spermine and the CaR-selective calcimimetic NPS R-467 were without effect. We conclude that small increases in divalent cation concentration elicit CaR-independent increases in TER and inhibit passive Ca2+ transport across Caco-2 monolayers, most probably through a direct effect on tight junction permeability. Whilst it is known that the complete removal of Cao2+ lowers TER, here we show that Cao2+ addition actually increases TER in a concentration-dependent manner. Therefore, such Cao2+-sensitivity could modulate intestinal solute transport including the limiting of excess Ca2+ absorption. 相似文献
15.
The sensing of extracellular Ca2+ concentration ([Ca2+]o) and modulation of cellular processes associated with acute or sustained changes in [Ca2+]o are cell-type specific and mediated by the calcium sensing receptor (CaR). [Ca2+]o signalling requires protein kinase C (PKC), but the identity and role of PKC isoforms in CaR-mediated responses remain unclear. Here we show that high [Ca2+]o activated PKC-α and PKC-ε in parathyroid cells and in human embryonic kidney (HEK293) cells overexpressing the CaR (HEK-CaR) and that this response correlated with the CaR-dependent activation of mitogen-activated protein kinases ERK1/2. Activation of ERK1/2 by acute high [Ca2+]o required influx of Ca2+through Ni2+-sensitive Ca2+channels and phosphatidylinositol-dependent phospholipase C-β activity. Inhibition of PKC by co-expression of dominant-negative (DN) mutants of PKC-α or -ε with the CaR attenuated sustained ERK1/2 activation. Overexpression of a PKC phosphorylation site (T888A) mutant CaR in HEK293 cells showed that this site was important for ERK1/2 activation at high [Ca2+]o. Activation of ERK1/2 by high [Ca2+]o was not necessary for the [Ca2+]o-regulated secretion of parathyroid hormone (PTH) in dispersed bovine parathyroid cells. These data suggest that the CaR-mediated [Ca2+]o signal leading to regulated PTH secretion that requires diacylglycerol-responsive PKC isoforms is not mediated via the ERK pathway. 相似文献
16.
《BBA》2001,1503(1-2):112-122
The parallel polarization electron paramagnetic resonance (EPR) method has been applied to investigate manganese EPR signals of native S1 and S3 states of the water oxidizing complex (WOC) in photosystem (PS) II. The EPR signals in both states were assigned to thermally excited states with S=1, from which zero-field interaction parameters D and E were derived. Three kinds of signals, the doublet signal, the singlet-like signal and g=11–15 signal, were detected in Ca2+-depleted PS II. The g=11–15 signal was observed by parallel and perpendicular modes and assigned to a higher oxidation state beyond S2 in Ca2+-depleted PS II. The singlet-like signal was associated with the g=11–15 signal but not with the YZ (the tyrosine residue 161 of the D1 polypeptide in PS II) radical. The doublet signal was associated with the YZ radical as proved by pulsed electron nuclear double resonance (ENDOR) and ENDOR-induced EPR. The electron transfer mechanism relevant to the role of YZ radical was discussed. 相似文献
17.
The calcium sensing receptor (CaR) is a G-protein-coupled receptor that is activated by extracellular calcium ([Ca2+]o). In MCF-7 human breast cancer cells, we previously reported that treatment with [Ca2+]o for 24 h leads to an over-expression of the Transient Receptor Potential Canonical 1 (TRPC1) cation channel and cell proliferation. Both involve the extracellular signal-regulated Kinases 1 & 2 (ERK1/2). MCF-7 also expressed epidermal growth factor receptor (EGFR) which is involved in cell proliferation through ERK1/2. Therefore, we investigated the cross-talk between CaR and EGFR in mediating ERK1/2 phosphorylation, TRPC1 over-expression and cell proliferation. Our data show that both high [Ca2+]o and EGF phosphorylate ERK1/2. Furthermore, inhibition of EGFR kinase and matrix metalloproteinases (MMPs) reduced the overall effects mediated by [Ca2+]o such as activation of ERK1/2, expression of TRPC1 and cell proliferation. They indicate the important role of the CaR-EGFR-ERK axis in transmitting mitogenic signals generated by high [Ca2+]o in MCF-7 cells. 相似文献
18.
Effects of melanins obtained from cultured Cladosporium cladosporidae fungi and Alpha grape on Fe2+-induced, Fe2+–ascorbate-induced, and NADPH-induced lipid peroxidation in rat liver, brain, and eye were studied. Melanins were shown to inhibit the accumulation of lipid peroxidation products in vitro. The inhibitory effects of melanins were not due to direct interactions of these pigments with superoxide anion (O
2
). However, melanins may interact with other free radicals. Melanins were demonstrated to have the ability to oxidize NADPH, which is probably one of the mechanisms of their antioxidant effects. 相似文献
19.
J. V. Milligan 《The Journal of general physiology》1965,48(5):841-858
Using area under the contracture curve to quantitate contractures, the diffusion coefficient of calcium ions within the frog toe muscle during washout in a calcium-free solution and subsequent recovery after reintroduction of calcium to the bathing solution was calculated to be about 2 x 10-6 cm2/sec. The diffusion coefficient measured during washout was found to be independent of temperature or initial calcium ion concentration. During recovery it was found to decrease if the temperature was lowered. This was likely due to the repolarization occurring after the depolarizing effect of the calcium-free solution. The relation between contracture area and [Ca]o was found to be useful over a wider range than that between maximum tension and [Ca]o. The normalized contracture areas were larger at lower calcium concentrations if the contractures were produced with cold potassium solutions or if NO3 replaced Cl in the bathing solutions. Decreasing the potassium concentration of the contracture solution to 50 mM from 115 mM did not change the relation between [Ca]o and the normalized area. If the K concentration of the bathing solution was increased, the areas were decreased at lower concentrations of Ca. 相似文献
20.
During the conversion of newt iris epithelial cells into lens cells, melanosomes disappear from the cytoplasm. In this “depigmentation,” exocytosis of melanosomes is involved. The role of Ca2+ in this process has been the subject of this work. The intracellular Ca2+ concentration of cultured iris epithelial cells was increased by three methods: microinjection of 10?3, M CaCl2 into the cytoplasm, fusion of phospholipid vesicles containing 10?3, M CaCl2 with the cell membrane, and exposure to the calcium ionophore A23187. Each of these treatments caused an increase in the release of melanosomes. Further experiments suggest that cAMP stimulates exocytosis probably by liberating Ca2+ from intracellular stores. 相似文献