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排序方式: 共有338条查询结果,搜索用时 93 毫秒
91.
Wataru Masuda Matthew J. Betzenhauser David I. Yule 《The Journal of biological chemistry》2010,285(48):37927-37938
Ca2+ release through inositol 1,4,5-trisphosphate receptors (InsP3R) can be modulated by numerous factors, including input from other signal transduction cascades. These events shape the spatio-temporal characteristics of the Ca2+ signal and provide fidelity essential for the appropriate activation of effectors. In this study, we investigate the regulation of Ca2+ release via InsP3R following activation of cyclic nucleotide-dependent kinases in the presence and absence of expression of a binding partner InsP3R-associated cGMP kinase substrate (IRAG). cGMP-dependent kinase (PKG) phosphorylation of only the S2+ InsP3R-1 subtype resulted in enhanced Ca2+ release in the absence of IRAG expression. In contrast, IRAG bound to each InsP3R subtype, and phosphorylation of IRAG by PKG attenuated Ca2+ release through all InsP3R subtypes. Surprisingly, simply the expression of IRAG attenuated phosphorylation and inhibited the enhanced Ca2+ release through InsP3R-1 following cAMP-dependent protein kinase (PKA) activation. In contrast, IRAG expression did not influence the PKA-enhanced activity of the InsP3R-2. Phosphorylation of IRAG resulted in reduced Ca2+ release through all InsP3R subtypes during concurrent activation of PKA and PKG, indicating that IRAG modulation is dominant under these conditions. These studies yield mechanistic insight into how cells with various complements of proteins integrate and prioritize signals from ubiquitous signaling pathways. 相似文献
92.
93.
Bruce JI Giovannucci DR Blinder G Shuttleworth TJ Yule DI 《The Journal of biological chemistry》2004,279(13):12909-12917
Parotid acinar cells exhibit rapid cytosolic calcium signals ([Ca2+]i) that initiate in the apical region but rapidly become global in nature. These characteristic [Ca2+]i signals are important for effective fluid secretion, which critically depends on a synchronized activation of spatially separated ion fluxes. Apically restricted [Ca2+]i signals were never observed in parotid acinar cells. This is in marked contrast to the related pancreatic acinar cells, where the distribution of mitochondria has been suggested to contribute to restricting [Ca2+]i signals to the apical region. Therefore, the aim of this study was to determine the mitochondrial distribution and the role of mitochondrial Ca2+ uptake in shaping the spatial and temporal properties of [Ca2+]i signaling in parotid acinar cells. Confocal imaging of cells stained with MitoTracker dyes (MitoTracker Green FM or MitoTracker CMXRos) and SYTO dyes (SYTO-16 and SYTO-61) revealed that a majority of mitochondria is localized around the nucleus. Carbachol (CCh) and caged inositol 1,4,5-trisphosphate-evoked [Ca2+]i signals were delayed as they propagated through the nucleus. This delay in the CCh-evoked nuclear [Ca2+]i signal was abolished by inhibition of mitochondrial Ca2+ uptake with ruthenium red and Ru360. Likewise, simultaneous measurement of [Ca2+]i with mitochondrial [Ca2+] ([Ca2+]m), using fura-2 and rhod-FF, respectively, revealed that mitochondrial Ca2+ uptake was also inhibited by ruthenium red and Ru360. Finally, at concentrations of agonist that evoke[Ca2+]i oscillations, mitochondrial Ca2+ uptake, and a nuclear [Ca2+] delay, CCh also evoked a substantial increase in NADH autofluorescence. This autofluorescence exhibited a predominant perinuclear localization that was also sensitive to mitochondrial inhibitors. These data provide evidence that perinuclear mitochondria and mitochondrial Ca2+ uptake may differentially shape nuclear [Ca2+] signals but more importantly drive mitochondrial metabolism to generate ATP close to the nucleus. These effects may profoundly affect a variety of nuclear processes in parotid acinar cells while facilitating efficient fluid secretion. 相似文献
94.
Sneyd J Tsaneva-Atanasova K Bruce JI Straub SV Giovannucci DR Yule DI 《Biophysical journal》2003,85(3):1392-1405
We construct a mathematical model of Ca(2+) wave propagation in pancreatic and parotid acinar cells. Ca(2+) release is via inositol trisphosphate receptors and ryanodine receptors that are distributed heterogeneously through the cell. The apical and basal regions are separated by a region containing the mitochondria. In response to a whole-cell, homogeneous application of inositol trisphosphate (IP(3)), the model predicts that 1), at lower concentrations of IP(3), the intracellular waves in pancreatic cells begin in the apical region and are actively propagated across the basal region by Ca(2+) release through ryanodine receptors; 2), at higher [IP(3)], the waves in pancreatic and parotid cells are not true waves but rather apparent waves, formed as the result of sequential activation of inositol trisphosphate receptors in the apical and basal regions; 3), the differences in wave propagation in pancreatic and parotid cells can be explained in part by differences in inositol trisphosphate receptor density; 4), in pancreatic cells, increased Ca(2+) uptake by the mitochondria is capable of restricting Ca(2+) responses to the apical region, but that this happens only for a relatively narrow range of [IP(3)]; and 5), at higher [IP(3)], the apical and basal regions of the cell act as coupled Ca(2+) oscillators, with the basal region partially entrained to the apical region. 相似文献
95.
96.
CM Galmarini A Kertesz R Oliva J Porta F C Galmarini 《Cancer immunology, immunotherapy : CII》1998,15(4):282-285
Bone metastasis in the hand is rare. The etiology is quite different from that of metastasis to other bones; bronchogenic
carcinoma is by far the most frequent case. Distal phalanges are mainly involved with irregular osteolysis and cortical destruction.
Differential diagnosis of phalangeal metastasis includes osteomyelitis, rheumatoid arthritis and gout. The prognosis is always
that of metastatic bronchial cancer with an average survival of three months. Treatment may involve distal digital amputation
or antalgic radiotherapy. A case of bronchogenic carcinoma with metastasis to the thumb is presented. The metastasis was located
in the distal phalanx of the left thumb. The primary tumor was located in the lung. Treatment consisted of amputation. The
overall survival was five months. 相似文献
97.
Microsatellite variation in Drosophila melanogaster and Drosophila simulans: a reciprocal test of the ascertainment bias hypothesis 总被引:2,自引:1,他引:1
Interspecific comparisons of microsatellite loci have repeatedly shown that
the loci are longer and more variable in the species from which they are
derived (the focal species) than are homologous loci in other (nonfocal)
species. There is debate as to whether this is due to directional evolution
or to an ascertainment bias during the cloning and locus selection
processes. This study tests these hypotheses by performing a reciprocal
study. Eighteen perfect dinucleotide microsatellite loci identified from a
Drosophila simulans library screen and 18 previously identified in an
identical Drosophila melanogaster library screen were used to survey
natural populations of each species. No difference between focal and
nonfocal species was observed for mean PCR fragment length. However,
heterozygosity and number of alleles were significantly higher in the focal
species than in the nonfocal species. The most common allele in the
Zimbabwe population of both species was sequenced for 31 of the 36 loci.
The length of the longest stretch of perfect repeat units is, on average,
longer in the focal species than in the non-focal species. There is a
positive correlation between the length of the longest stretch of perfect
repeats and heterozygosity. The difference in heterozygosity can thus be
explained by a reduction in the length of the longest stretch of perfect
repeats in the nonfocal species. Furthermore, flanking-sequence length
difference was noted between the two species at 58% of the loci sequenced.
These data do not support the predictions of the directional-evolution
hypothesis; however, consistent with the ascertainment bias hypothesis, the
lower variability in nonfocal species is an artifact of the microsatellite
cloning and isolation process. Our results also suggest that the magnitude
of ascertainment bias for repeat unit length is a function of the
microsatellite size distribution in the genomes of different species.
相似文献
98.
Prospects for estimating nucleotide divergence with RAPDs 总被引:11,自引:0,他引:11
The technique of random amplification of polymorphic DNA (RAPD), which is
simply polymerase chain reaction (PCR) amplification of genomic DNA by a
single short oligonucleotide primer, produces complex patterns of anonymous
polymorphic DNA fragments. The information provided by these banding
patterns has proved to be of great utility for mapping and for verification
of identity of bacterial strains. Here we consider whether the degree of
similarity of the banding patterns can be used to estimate nucleotide
diversity and nucleotide divergence. With haploid data, fragments generated
by RAPD-PCR can be treated in a fashion very similar to that for
restriction-fragment data. Amplification of diploid samples, on the other
hand, requires consideration of the fact that presence of a band is
dominant to absence of the band. After describing a method for estimating
nucleotide divergence on the basis of diploid samples, we summarize the
restrictions and criteria that must be met when RAPD data are used for
estimating population genetic parameters.
相似文献
99.
100.
The plant innate immune response includes the hypersensitive response (HR), a form of programmed cell death (PCD). PCD must be restricted to infection sites to prevent the HR from playing a pathologic rather than protective role. Here we show that plant BECLIN 1, an ortholog of the yeast and mammalian autophagy gene ATG6/VPS30/beclin 1, functions to restrict HR PCD to infection sites. Initiation of HR PCD is normal in BECLIN 1-deficient plants, but remarkably, healthy uninfected tissue adjacent to HR lesions and leaves distal to the inoculated leaf undergo unrestricted PCD. In the HR PCD response, autophagy is induced in both pathogen-infected cells and distal uninfected cells; this is reduced in BECLIN 1-deficient plants. The restriction of HR PCD also requires orthologs of other autophagy-related genes including PI3K/VPS34, ATG3, and ATG7. Thus, the evolutionarily conserved autophagy pathway plays an essential role in plant innate immunity and negatively regulates PCD. 相似文献