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61.
A comparative functional analysis of plasma membrane Ca2+ pump isoforms in intact cells 总被引:2,自引:0,他引:2
Brini M Coletto L Pierobon N Kraev N Guerini D Carafoli E 《The Journal of biological chemistry》2003,278(27):24500-24508
The four basic isoforms of the plasma membrane Ca2+ pump and the two C-terminally truncated spliced variants PMCA4CII(4a) and 3CII(3a) were transiently overexpressed in Chinese hamster ovary cells together with aequorin targeted to the cytosol, the endoplasmic reticulum, and the mitochondria. As PMCA3CII(3a) had not yet been cloned and studied, it was cloned for this study, partially purified, and characterized. At variance with the corresponding truncated variant of PMCA4, which had been studied previously, PMCA3CII(3a) had very high calmodulin affinity. All four basic pump variants influenced the homeostasis of Ca2+ in the native intracellular environment. The level of [Ca2+] in the endoplasmic reticulum and the height of the [Ca2+] transients generated in the cytosol and in the mitochondria by the emptying of the endoplasmic reticulum store by inositol 1,4,5-trisphosphate were all reduced by the overexpression of the pumps. The effects were much greater with the neuron-specific PMCA2 and PMCA3 than with the ubiquitously expressed isoforms 1 and 4. Unexpectedly, the truncated PMCA3 and PMCA4 were as effective as the full-length variants in influencing the homeostasis of Ca2+ in the cytosol and the organelles. In particular, PMCA4CII(4a) was as effective as PMCA4CI(4b), even if its affinity for calmodulin is much lower. The results indicate that the availability of calmodulin may not be critical for the modulation of PMCA pumps in vivo. 相似文献
62.
63.
The initial rate of Fe(2+) movement across the inner envelope membrane of pea (Pisum sativum) chloroplasts was directly measured by stopped-flow spectrofluorometry using membrane vesicles loaded with the Fe(2+)-sensitive fluorophore, Phen Green SK. The rate of Fe(2+) transport was rapid, coming to equilibrium within 3s. The maximal rate and concentration dependence of Fe(2+) transport in predominantly right-side-out vesicles were nearly equivalent to those measured in largely inside-out vesicles. Fe(2+) transport was stimulated by an inwardly directed electrochemical proton gradient across right-side-out vesicles, an effect that was diminished by the addition of valinomycin in the presence of K(+). Fe(2+) transport was inhibited by Zn(2+), in a competitive manner, as well as by Cu(2+) and Mn(2+). These results indicate that inward-directed Fe(2+) transport across the chloroplast inner envelope occurs by a potential-stimulated uniport mechanism. 相似文献
64.
Porter D Lahti-Domenici J Torres-Arzayus M Chin L Polyak K 《Mechanisms of development》2002,114(1-2):201-204
We analyzed the expression of high in normal-1 (HIN-1), a putative breast tumor suppressor gene, and uteroglobin related protein-1 (UGRP-1), a homologue of HIN-1, in adult and developing mouse tissues. Highest HIN-1 and UGRP-1 expression is detected in the lung, while lower level HIN-1 expression is also detected in the stomach, heart, small intestine, uterine and mammary glands. The expression of both genes was detected only at E17.5-18.5 and the HIN-1 messenger RNA was localized to the epithelia of the trachea, bronchi, and uterine glands. The expression of HIN-1 is up-regulated during retinoic acid induced differentiation of bronchial epithelial cells. We also identified two putative Drosophila HIN-1 homologues. The expression of HIN-1 is restricted to terminally differentiated airway epithelial cells in vivo and in vitro implicating HIN-1 in the acquisition or maintenance of terminally differentiated epithelial phenotype. 相似文献
65.
Delporte C Muñoz O Rojas J Ferrándiz M Payá M Erazo S Negrete R Maldonado S San FA Backhouse N 《Zeitschrift für Naturforschung. C, Journal of biosciences》2002,57(1-2):100-108
The probable antipyretic, antiinflammatory, analgesic and antioxidant properties of Kageneckia oblonga, Rosaceae, were investigated and the major compounds of its active extracts were isolated. The study comprised the acute toxicity of the extracts of global methanol, hexane, dichloromethane and methanol. The cytotoxicity of global methanol extract was studied in three tumoral cell lines. All the extracts exhibited the pharmacological activities under study. Methanol and dichloromethane were the most toxic extracts. From the global methanol extract, isolations were performed of prunasin, 23,24- dihydro-cucurbitacin F, and a new cucurbitacin, 3beta-(beta-D-glucosyloxy)-16alpha,23alpha-epoxycucurbita-5,24-diene-11-one. The cytotoxicity of both cucurbitacins on human neutrophils at the assayed concentrations was not statistically significant. In-vitro assays showed that both cucurbitacins can be partly responsible for the analgesic, antipyretic, and anti-inflammatory activities. Evaluation was done of the cytotoxicity of global methanol extract, 23, 24-dihydrocucurbitacin F, aqueous extracts and prunasin against P-388 murine leukaemia, A-549 human lung carcinoma and HT-29 colon carcinoma. Since global methanol extract presented a strong cytotoxicity against P-388 murine leukaemia, A-549 human lung carcinoma, and HT-29 cell lines, it is highly probable that this extract contain one or more cytotoxic compounds that could be investigated for their potential use as an agent against cancer. 相似文献
66.
Motura MI Moroni GN Teijeiro SA Salomón H Briñón MC 《Nucleosides, nucleotides & nucleic acids》2002,21(3):217-230
Synthesis, solid state characterization and anti HIV-1 activity of 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine (2), a new prodrug of zidovudine (AZT, 1), are described. Two solid forms of 2 prepared by crystallization from ethyl acetate-petroleum ether (form alpha) and from a melt sample of form alpha (amorphous form) were characterized by X-ray diffractometry, infrared spectroscopy, differential scanning calorimetry (DSC) and thermogravimetry (TGA) techniques. The novel nucleoside exhibited antiviral activity against standard and resistant strain panels of HIV-1 as well as cytotoxicity similar to that of AZT. 相似文献
67.
Developing seeds of Arabidopsis store different minerals in two types of vacuoles and in the endoplasmic reticulum 总被引:12,自引:0,他引:12
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Mineral-accumulating compartments in developing seeds of Arabidopsis were studied using high-pressure-frozen/freeze-substituted samples. Developing seeds store minerals in three locations: in the protein storage vacuoles of the embryo, and transiently in the endoplasmic reticulum (ER) and vacuolar compartments of the chalazal endosperm. Energy dispersive x-ray spectroscopy and enzyme treatments suggest that the minerals are stored as phytic acid (myo-inositol-1,2,3,4,5,6-hexakisphosphate) salts in all three compartments, although they differ in cation composition. Whereas embryo globoids contain Mg, K, and Ca as cations, the chalazal ER deposits show high levels of Mn, and the chalazal vacuolar deposits show high levels of Zn. The appearance of the first Zn-phytate crystals coincides with the formation of network-like extensions of the chalazal vacuoles. The core of these networks consists of a branched network of tubular ER membranes, which are separated from the delineating tonoplast membranes by a layer of cytosolic material. Degradation of the networks starts with the loss of the cytosol and is followed by the retraction of the ER, generating a network of collapsed tonoplast membranes that are resorbed. Studies of fertilized fis2 seeds, which hyperaccumulate Zn-phytate crystals in the chalazal vacuolar compartments, suggest that only the intact network is active in mineral sequestration. Mineral determination analysis and structural observations showed that Zn and Mn are mobilized from the endosperm to the embryo at different developmental stages. Thus, Zn appears to be removed from the endosperm at the late globular stage, and Mn stores appear to be removed at the late bent-cotyledon stage of embryo development. The disappearance of the Mn-phytate from the endosperm coincides with the accumulation of two major Mn binding proteins in the embryo, the 33-kD protein from the oxygen-evolving complex of photosystem II and the Mn superoxide dismutase. The possible functions of transient heavy metal storage in the chalazal endosperm are discussed. A model showing how phytic acid, a potentially cytotoxic molecule, is transported from its site of synthesis, the ER, to the different mineral storage sites is presented. 相似文献
68.
Analysis of sequence upstream of the endogenous H19 gene reveals elements both essential and dispensable for imprinting
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Thorvaldsen JL Mann MR Nwoko O Duran KL Bartolomei MS 《Molecular and cellular biology》2002,22(8):2450-2462
Imprinting of the linked and oppositely expressed mouse H19 and Igf2 genes requires a 2-kb differentially methylated domain (DMD) that is located 2 kb upstream of H19. This element is postulated to function as a methylation-sensitive insulator. Here we test whether an additional sequence 5' of H19 is required for H19 and Igf2 imprinting. Because repetitive elements have been suggested to be important for genomic imprinting, the requirement of a G-rich repetitive element that is located immediately 3' to the DMD was first tested in two targeted deletions: a 2.9-kb deletion (Delta D MD Delta G) that removes the DMD and G-rich repeat and a 1.3-kb deletion (Delta G) removing only the latter. There are also four 21-bp GC-rich repetitive elements within the DMD that bind the insulator-associated CTCF (CCCTC-binding factor) protein and are implicated in mediating methylation-sensitive insulator activity. As three of the four repeats of the 2-kb DMD were deleted in the initial 1.6-kb Delta DMD allele, we analyzed a 3.8-kb targeted allele (Delta 3.8kb-5'H19), which deletes the entire DMD, to test the function of the fourth repeat. Comparative analysis of the 5' deletion alleles reveals that (i) the G-rich repeat element is dispensable for imprinting, (ii) the Delta DMD and Delta DMD Delta G alleles exhibit slightly more methylation upon paternal transmission, (iii) removal of the 5' CTCF site does not further perturb H19 and Igf2 imprinting, suggesting that one CTCF-binding site is insufficient to generate insulator activity in vivo, (iv) the DMD sequence is required for full activation of H19 and Igf2, and (v) deletion of the DMD disrupts H19 and Igf2 expression in a tissue-specific manner. 相似文献
69.
70.
Clb5-associated Kinase Activity is Required Early in the Spindle Pathway for Correct Preanaphase Nuclear Positioning in Saccharomyces cerevisiae 总被引:1,自引:0,他引:1
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In Saccharomyces cerevisiae, a single cyclin-dependent kinase, Cdc28, regulates both G1/S and G2/M phase transitions by associating with stage-specific cyclins. During progression through S phase and G2/M, Cdc28 is activated by the B-type cyclins Clb1–6. Because of functional redundancy, specific roles for individual Clbs have been difficult to assign. To help genetically define such roles, strains carrying a cdc28ts allele, combined with single CLB deletions were studied. We assumed that by limiting the activity of the kinase, these strains would be rendered more sensitive to loss of individual Clbs. 相似文献