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141.
Calcium/Calmodulin-Stimulated Protein Kinase II Is Present in Primary Cultures of Cerebral Endothelial Cells 总被引:1,自引:0,他引:1
Mária A. Deli Ferenc Joó István Krizbai Imre Lengyel Maria G. Nunzi Joachim R. Wolff† 《Journal of neurochemistry》1993,60(5):1960-1963
Abstract: Calcium/calmodulin-stimulated protein kinase II (CaMPK II). a major kinase in brain, has been established to play an important role in neurotransmitter release and organization of postsynaptic receptors, and it is known to be involved in long-term potentiation and memory. Less is known about the function of this enzyme in nonneural cells. Here we report on the production, presence, and phosphorylation of the α-subunit of CaM-PK II in primary cultures of cerebral endothelial cells. These results raise the possibility that α-CaM-PK II can act as one of the key enzymes of calcium-mediated intracellular signaling in the cerebral endothelial cells and suggest that α-CaM-PK II may participate in such basic cellular processes as permeability in physiological and pathological conditions. 相似文献
142.
L.-Y. Chau T. A. Lin W.-T. Chang C.-H. Chen M.-J. Shue Y.-S. Hsu C.-Y. Hu W.-H. Tsai G. Y. Sun 《Journal of neurochemistry》1993,60(2):454-460
Abstract: Addition of endothelins (ETs) to neuroblastomaglioma hybrid cells (NG108-15) induced increases in cytosolic free Ca2+ ([Ca2+]i) levels of labeled inositol monophosphates and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. The increases in [Ca2+]i elicited by the three ETs (ET-1, ET-2, and ET-3) were transient and did not show a sustained phase. Chelating extracellular Ca2+ in the medium by adding excess EGTA decreased the ET-mediated Ca2+ response by 40-50%. This result indicates that a substantial portion of the increase in [Ca2+]i was due to influx from an extracellular source. However, the increase in [Ca2+]i was not affected by verapamil or nifedipine (10?5M). A rank order potency of ET-1 ET-2 ET-3 is shown for the stimulated increase in [Ca2+]i, as well as labeled inositol phosphates, in these cells. ATP (10?4M) and bradykinin (10?7M) also induced the increases in [Ca2+]i and Ins(1,4,5)P3 in NG108-15 cells, albeit to a different extent. When compared at 10?7M, bradykinin elicited a five- to sixfold higher increase in the level of Ins(1,4,5)P3, but less than a twofold higher increase in [Ca2+]i than those induced by ET-1. Additive increases in both Ins(1,4,5)P3 and [Ca2+]i were observed when ET-1, ATP, and bradykinin were added to the cells in different combinations, suggesting that each receptor agonist is responsible for the hydrolysis of a pool of polyphosphoinositide within the membrane. ET-1 exhibited homologous desensitization of the Ca2+ response, but partial heterologous desensitization to the Ca2+ response elicited by ATP. On the contrary, ET-1 did not desensitize the response elicited by bradykinin, although bradykinin exhibited complete heterologous desensitization to the response elicited by ET-1. Taken together, these results illustrate that, in NG108-15 cells, a considerable amount of receptor cross talk occurs between ET and other receptors that transmit signals through the polyphosphoinositide pathway. 相似文献
143.
Jacques J. H. Hens Marina De Wit Lodewijk V. Dekker Frans Boomsma A. Beate Oestreicher Frank Margolis† Willem Hendrik Gispen Pierre N. E. De Graan 《Journal of neurochemistry》1993,60(4):1264-1273
Abstract: The involvement of B-50, protein kinase C (PKC), and PKC-mediated B-50 phosphorylation in the mechanism of Ca2+-induced noradrenaline (NA) release was studied in highly purified rat cerebrocortical synaptosomes permeated with streptolysin-O. Under optimal permeation conditions, 12% of the total NA content (8.9 pmol of NA/mg of synaptosomal protein) was released in a largely (>60%) ATP-dependent manner as a result of an elevation of the free Ca2+ concentration from 10?8 to 10?5M Ca2+ The Ca2+ sensitivity in the micromolar range is identical for [3H]NA and endogenous NA release, indicating that Ca2+-induced [3H]NA release originates from vesicular pools in noradrenergic synaptosomes. Ca2+-induced NA release was inhibited by either N- or C-terminal-directed anti-B-50 antibodies, confirming a role of B-50 in the process of exocytosis. In addition, both anti-B-50 antibodies inhibited PKC-mediated B-50 phosphorylation with a similar difference in inhibitory potency as observed for NA release. However, in a number of experiments, evidence was obtained challenging a direct role of PKC and PKC-mediated B-50 phosphorylation in Ca2+-induced NA release. PKC pseudosubstrate PKC19-36, which inhibited B-50 phosphorylation (IC50 value, 10?5M), failed to inhibit Ca2+-induced NA release, even when added before the Ca2+ trigger. Similar results were obtained with PKC inhibitor H-7, whereas polymyxin B inhibited B-50 phosphorylation as well as Ca2+-induced NA release. Concerning the Ca2+ sensitivity, we demonstrate that PKC-mediated B-50 phosphorylation is initiated at a slightly higher Ca2+ concentration than NA release. Moreover, phorbol ester-induced PKC down-regulation was not paralleled by a decrease in Ca2+-induced NA release from streptolysin-O-permeated synaptosomes. Finally, the Ca2+- and phorbol ester-induced NA release was found to be additive, suggesting that they stimulate release through different mechanisms. In summary, we show that B-50 is involved in Ca2+-induced NA release from streptolysin-O-permeated synaptosomes. Evidence is presented challenging a role of PKC-mediated B-50 phosphorylation in the mechanism of NA exocytosis after Ca2+ influx. An involvement of PKC or PKC-mediated B-50 phosphorylation before the Ca2+ trigger is not ruled out. We suggest that the degree of B-50 phosphorylation, rather than its phosphorylation after PKC activation itself, is important in the molecular cascade after the Ca2+ influx resulting in exocytosis of NA. 相似文献
144.
Abstract: The effect of phloretin on prostaglandin (PG) F2α -induced phosphoinositide hydrolysis and elevation of intracellular Ca2+ concentration was examined in cultured rat astrocytes. Phloretin inhibited PGF2α (1 μ M )-induced phosphoinositide hydrolysis in a concentration-dependent manner with an IC50 value of 16 μ M . The inhibitory action of phloretin was specific for PGs. The addition of increasing concentrations of phloretin caused progressive shifts of the dose-response curves of PGF2α to the right. In digitoninpermeabilized astrocytes, phloretin (100 μ M ) inhibited the stimulation induced by PGF2α (1 μ M ) plus GTPγS (50 μ M ) without affecting that induced by GTPγS alone. PGF2α at 1 μ M transiently increased astrocytic intracellular Ca2+ concentration in 39% of the cells tested. The response was completely blocked by 100 μ M phloretin and the calcium response recovered again after washing out phloretin. These results suggest that phloretin is an antagonist of PGF2α receptor linked to phospholipase C in astrocytes. 相似文献
145.
146.
Calcium deficiency in zucchini (Cucurbita pepo L.) is associated with reduced growth and a reduced ability to transport auxin (Allan and Rubery, 1991, Planta 183, 604–612). An investigation of the effects of calcium-deficiency on zucchini hypocotyl cells was made using weak-acid uptake
and 31P-nuclear-magneticresonance (31P-NMR) spectroscopy in vivo and in tissue extracts. Calcium-deficient tissue had the same cytoplasmic and vacuolar pHs as
normal tissue when extracellular pH was near neutral. At acidic external pH the vacuolar pH was lower in deficient tissue.
Adenine nucleotides were present predominantly as ATP in both control and calcium-deficient tissues. Addition of calcium to
calcium-deficient tissue, under conditions which cause recovery of auxin transport induced no changes in the 31P-NMR spectra of deficient tissue. The content of mobile, phosphorylated metabolites was reduced in calcium-deficient tissue
in comparison to control tissue. However, a substantial increase in the content of phosphorylcholine occurs in calcium-deficient
tissues compared with controls; this may reflect changes in lipid turnover in calcium-stressed cells.
We wish to thank Drs. Terry Moore and Jamie Vandenberg for technical assistance and Professor Peter Morris for providing the
gated oxygen device. A.C.A. thanks the Cambridge Commonwealth Trust for a Prince of Wales Scholarship and the O.R.S. Awards
Scheme for an award. 相似文献
147.
Several mineral rhizotoxicities, including those induced by Al3+, H+, and Na+, can be relieved by elevated Ca2+ in the rooting medium. This leads to the hypothesis that the toxic cations displace Ca2+ from transport channels or surface ligands that must be occupied by Ca2+ in order for root elongation to occur. In this study with wheat (Triticum aestivum L.) seedlings, we have determined, in the case of Al3+, that (i) Ca2+, Mg2+, and Sr2+ are equally ameliorative, (ii) that root elongation does not increase as Ca2+ replaces Mg2+ or Sr2+ in the rooting media, and (iii) that rhizotoxicity is a function solely of Al3+ activity at the root-cell membrane surface as computed by a Gouy-Chapman-Stern model. The rhizotoxicity was indifferent to the computed membrane-surface Ca2+ activity. The rhizotoxicity induced by high levels of tris(ethylenediamine)cobaltic ion (TEC3+), in contrast to Al3+, was specifically relieved by Ca2+ at the membrane surface. The rhizotoxicity induced by H+ exhibited a weak specific response to Ca2+ at the membrane surface. We conclude that the Ca2+-displacement hypothesis fails in the case of Al3+ rhizotoxicity and that amelioration by cations (including monovalent cations) occurs because of decreased membrane-surface negativity and the consequent decrease in the membrane-surface activity of Al3+. However, TEC3+, but not Al3+, may be toxic because it inhibits Ca2+ uptake. The nature of the specific H+-Ca2+ interaction is uncertain.Abbreviations {Al3+ }0
chemical activity of Al3+ at the root-cell membrane surface
- {Al3+ }E
chemical activity of Al3+ in the external rooting medium
- E0
electrical potential at the root-cell membrane surface
- HXM2+
hexamethonium ion
- TEC3+
tris(ethylenediamine)cobaltic ion 相似文献
148.
Mitsuo Matsuda Toshiya Nosaka Masaaki Sato Norio Ohshima 《European journal of applied physiology and occupational physiology》1993,66(2):122-126
To evaluate the effects of exercise on aortic wall elasticity and elastic components, young male rats underwent various exercise regimes for 16 weeks. In the exercised rats, the aortic incremental elastic modulus decreased significantly when under physiological strain. The aortic content of elastin increased significantly and the calcium content of elastin decreased significantly in the exercised group. The accumulated data from the exercised and sedentary groups revealed that the elastin calcium content was related positively to the incremental elastic modulus. We concluded that physical exercise from an early age decreases the calcium deposit in aortic wall elastin and that this effect probably produced in the exercised rats a distensible aorta. 相似文献
149.
To determine whether lipid-secreting cells have cytosolic Ca2+ concentration ([Ca2+]c)-related secretory mechanisms, morphological changes and intracellular calcium dynamics of Harderian glands of guinea pigs stimulated by secretagogs were studied by electron microspy and Fura-2/AM digital image analysis. Control glandular cells contained large lipid vacuoles that were bordered by multi-layered membranes. Rough-surfaced endoplasmic reticulum, mitochondria, and smooth-surfaced endoplasmic reticulum may be involved in lipid vacuole formation. Myoepithelial cells surrounded alveoli. After carbamylcholine (CCh, 10–6, 10–5, and 10–3 M) stimulation, lipid materials within the membranous structures were frequently discharged by an exocytotic mechanism. Conspicuous deformation of glandular cells caused by vigorous contraction of myoepithelial cells was observed in isolated alveoli after 10–6M CCh stimulation, whereas the deformaties of glandular tissues perfused via vessels were small even after 10–3M CCh stimulation. Connective tissue between glandular alveoli inhibited unbridled myoepithelial-cell contraction. Fura-2/AM digital imaging analysis revealed that CCh stimulation caused an increase in [Ca2+]c in isolated alveoli. The morphological reactions and changes in [Ca2+]c were prevented by atropine. When extracellular calcium ions were absent, enhanced extrusion of lipid vacuoles, myoepithelial-cell contraction, and a rise in [Ca2+]c after CCh stimulation were not observed. Nicotine and catecholamines had no effect on the secretion or on the dynamics of [Ca2+]c. It can be concluded that acetylcholine elicits exocytosis in glandular cells and contraction of the myoepithelial cells of Harderian glands, accompanied by an increase in [Ca2+]c. The dynamics of [Ca2+]c of the gland alveoli are mostly dependent on extracellular Ca2+. 相似文献
150.
Reader domains that recognize methylated lysine and arginine residues on histones play a role in the recruitment, stabilization, and regulation of chromatin regulatory proteins. Targeting reader proteins with small molecule and peptidomimetic inhibitors has enabled the elucidation of the structure and function of specific domains and uncovered their role in diseases. Recent progress towards chemical probes that target readers of lysine methylation, including the Royal family and plant homeodomains (PHD), is discussed here. We highlight recently developed covalent cyclic peptide inhibitors of a plant homeodomain. Additionally, inhibitors targeting previously untargeted Tudor domains and chromodomains are discussed. 相似文献