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排序方式: 共有250条查询结果,搜索用时 15 毫秒
71.
Michael P. Young Zachary T. Schug David M. Booth David I. Yule Katsuhiko Mikoshiba Gyrgy HajnÌczky Suresh K. Joseph 《The Journal of biological chemistry》2022,298(1)
Calcium signaling is essential for regulating many biological processes. Endoplasmic reticulum inositol trisphosphate receptors (IP3Rs) and the mitochondrial Ca2+ uniporter (MCU) are key proteins that regulate intracellular Ca2+ concentration. Mitochondrial Ca2+ accumulation activates Ca2+-sensitive dehydrogenases of the tricarboxylic acid (TCA) cycle that maintain the biosynthetic and bioenergetic needs of both normal and cancer cells. However, the interplay between calcium signaling and metabolism is not well understood. In this study, we used human cancer cell lines (HEK293 and HeLa) with stable KOs of all three IP3R isoforms (triple KO [TKO]) or MCU to examine metabolic and bioenergetic responses to the chronic loss of cytosolic and/or mitochondrial Ca2+ signaling. Our results show that TKO cells (exhibiting total loss of Ca2+ signaling) are viable, displaying a lower proliferation and oxygen consumption rate, with no significant changes in ATP levels, even when made to rely solely on the TCA cycle for energy production. MCU KO cells also maintained normal ATP levels but showed increased proliferation, oxygen consumption, and metabolism of both glucose and glutamine. However, MCU KO cells were unable to maintain ATP levels and died when relying solely on the TCA cycle for energy. We conclude that constitutive Ca2+ signaling is dispensable for the bioenergetic needs of both IP3R TKO and MCU KO human cancer cells, likely because of adequate basal glycolytic and TCA cycle flux. However, in MCU KO cells, the higher energy expenditure associated with increased proliferation and oxygen consumption makes these cells more prone to bioenergetic failure under conditions of metabolic stress. 相似文献
72.
Chloride channels in the small intestinal cell line IEC-18 总被引:1,自引:0,他引:1
Basavappa S Vulapalli SR Zhang H Yule D Coon S Sundaram U 《Journal of cellular physiology》2005,202(1):21-31
Small intestinal crypt cells play a critical role in modulating Cl- secretion during digestion. The types of Cl- channels mediating Cl- secretion in the small intestine was investigated using the intestinal epithelial cell line, IEC-18, which was derived from rat small intestine crypt cells. In initial radioisotope efflux studies, exposure to forskolin, ionomycin or a decrease in extracellular osmolarity significantly increased 36Cl efflux as compared to control cells. Whole cell patch clamp techniques were subsequently used to examine in more detail the swelling-, Ca2+-, and cAMP-activated Cl- conductance. Decreasing the extracellular osmolarity from 290 to 200 mOsm activated a large outwardly rectifying Cl- current that was voltage-independent and had an anion selectivity of I- > Cl-. Increasing cytosolic Ca2+ by ionomycin activated whole cell Cl- currents, which were also outwardly rectifying but were voltage-dependent. The increase in intracellular Ca2+ levels with ionomycin was confirmed with fura-2 loaded IEC-18 cells. A third type of whole cell Cl- current was observed after increases in intracellular cAMP induced by forskolin. These cAMP-activated Cl- currents have properties consistent with cystic fibrosis transmembrane regulator (CFTR) Cl- channels, as the currents were blocked by glibenclamide or NPPB but insensitive to DIDS. In addition, the current-voltage relationship was linear and had an anion selectivity of Cl- > I-. Confocal immunofluorescence studies and Western blots with two different anti-CFTR antibodies confirmed the expression of CFTR. These results suggest that small intestinal crypt cells express multiple types of Cl- channels, which may all contribute to net Cl- secretion. 相似文献
73.
74.
John Wakefield R. Yule Alwyn Smith A. M. Adelstein 《BMJ (Clinical research ed.)》1973,2(5859):142-143
An analysis of the cytological records of almost 300,000 women in the Manchester area shows that the rates of positive/suspicious findings from population screening are highly correlated with the rates of mortality from cancer of the cervix when both are distributed according to the occupation of the husband. The correlation holds for various occupational groupings and for all the individual occupation units in which there are more than 1,000 women. This evidence strengthens the case for believing that the condition revealed by a positive smear is a stage in the development of invasive cancer of the uterine cervix. 相似文献
75.
Luz Boyero Richard G. Pearson Christopher M. Swan Cang Hui Ricardo J. Albariño Muthukumarasamy Arunachalam Marcos Callisto Julián Chará Ana M. Chará‐Serna Eric Chauvet Aydeé Cornejo David Dudgeon Andrea C. Encalada Verónica Ferreira Mark O. Gessner José F. Gonçalves Jr Manuel A. S. Graça Julie E. Helson Jude M. Mathooko Brendan G. McKie Marcelo S. Moretti Catherine M. Yule 《Ecography》2015,38(9):949-955
Understanding what mechanisms shape the diversity and composition of biological assemblages across broad‐scale gradients is central to ecology. Litter‐consuming detritivorous invertebrates in streams show an unusual diversity gradient, with α‐diversity increasing towards high latitudes but no trend in γ‐diversity. We hypothesized this pattern to be related to shifts in nestedness and several ecological processes shaping their assemblages (dispersal, environmental filtering and competition). We tested this hypothesis, using a global dataset, by examining latitudinal trends in nestedness and several indicators of the above processes along the latitudinal gradient. Our results suggest that strong environmental filtering and low dispersal in the tropics lead to often species‐poor local detritivore assemblages, nested in richer regional assemblages. At higher latitudes, dispersal becomes stronger, disrupting the nested assemblage structure and resulting in local assemblages that are generally more species‐rich and non‐nested subsets of the regional species pools. Our results provide evidence that mechanisms underlying assemblage composition and diversity of stream litter‐consuming detritivores shift across latitudes, and provide an explanation for their unusual pattern of increasing α‐diversity with latitude. When we repeated these analyses for whole invertebrate assemblages of leaf litter and for abundant taxa showing reverse or no diversity gradients we found no latitudinal patterns, suggesting that function‐based rather than taxon‐based analyses of assemblages may help elucidate the mechanisms behind diversity gradients. 相似文献
76.
77.
The costs and benefits of symbiotic interactions may vary with host and symbiont ontogeny. Effects of symbionts at different stages of host development or on different host demographic rates do not contribute equally to fitness. Although rarely applied, a population dynamics approach that integrates over the host life cycle is therefore necessary for capturing the net costs or benefits and, thus, the mutualistic or parasitic nature of symbioses. Using the native, disturbance‐specialist grass Agrostis hyemalis, we asked how a symbiotic endophyte affected the population dynamics of its host and how imperfect vertical transmission influenced symbiont frequency in a late successional environment. A size‐structured integral projection model (IPM) parameterized with experimental field data showed that greater rates of individual growth and reproduction for endophyte‐symbiotic (E+) hosts outweighed their lower rates of survival, leading to a net positive effect of symbiosis on equilibrium plant population growth (slower rate of extinction). Given that populations under going successional transitions are unlikely to be at an equilibrium size structure, we also conducted transient analysis that showed an initial short‐term cost to endophyte symbiosis. We used a megamatrix approach to link E? and E+ IPMs via imperfect vertical transmission and found that this parameter strongly influenced the frequency of symbiosis via complex interactions with host demographic rates. Overall, our population dynamics approach improves the ability to characterize the outcome of symbiotic interactions, and results suggest that particular attention should be paid to interactions between the rate of vertical transmission and host demography. 相似文献
78.
The multifunctional movement protein (MP) of Tomato mosaic tobamovirus (ToMV) is involved in viral cell-to-cell movement, symptom development, and resistance gene recognition. However, it remains to be elucidated how ToMV
MP plays such diverse roles in plants. Here, we show that ToMV
MP interacts with the Rubisco small subunit (RbCS) of Nicotiana benthamiana in vitro and in vivo. In susceptible N. benthamiana plants, silencing of NbRbCS enabled ToMV to induce necrosis in inoculated leaves, thus enhancing virus local infectivity. However, the development of systemic viral symptoms was delayed. In transgenic N. benthamiana plants harboring Tobacco mosaic virus resistance-22 (Tm-22), which mediates extreme resistance to ToMV, silencing of NbRbCS compromised Tm-22-dependent resistance. ToMV was able to establish efficient local infection but was not able to move systemically. These findings suggest that NbRbCS plays a vital role in tobamovirus movement and plant antiviral defenses.Plant viruses use at least one movement protein (MP) to facilitate viral spread between plant cells via plasmodesmata (PD; Lucas and Gilbertson, 1994; Ghoshroy et al., 1997). Among viral MPs, the MP of tobamoviruses, such as Tobacco mosaic virus (TMV) and its close relative Tomato mosaic virus (ToMV), is the best characterized. TMV
MP specifically accumulates in PD and modifies the plasmodesmatal size exclusion limit in mature source leaves or tissues (Wolf et al., 1989; Deom et al., 1990; Ding et al., 1992). TMV
MP and viral genomic RNA form a mobile ribonucleoprotein complex that is essential for cell-to-cell movement of viral infection (Watanabe et al., 1984; Deom et al., 1987; Citovsky et al., 1990, 1992; Kiselyova et al., 2001; Kawakami et al., 2004; Waigmann et al., 2007). TMV
MP also enhances intercellular RNA silencing (Vogler et al., 2008) and affects viral symptom development, host range, and host susceptibility to virus (Dardick et al., 2000; Bazzini et al., 2007). Furthermore, ToMV
MP is identified as an avirulence factor that is recognized by tomato (Solanum lycopersicum) resistance proteins Tobacco mosaic virus resistance-2 (Tm-2) and Tm-22 (Meshi et al., 1989; Lanfermeijer et al., 2004). Indeed, tomato Tm-22 confers extreme resistance against TMV and ToMV in tomato plants and even in heterologous tobacco (Nicotiana tabacum) plants (Lanfermeijer et al., 2003, 2004).To date, several host factors that interact with TMV
MP have been identified. These TMV
MP-binding host factors include cell wall-associated proteins such as pectin methylesterase (Chen et al., 2000), calreticulin (Meshi et al., 1989), ANK1 (Ueki et al., 2010), and the cellular DnaJ-like protein MPIP1 (Shimizu et al., 2009). Many cytoskeletal components such as actin filaments (McLean et al., 1995), microtubules (Heinlein et al., 1995), and the microtubule-associated proteins MPB2C (Kragler et al., 2003) and EB1a (Brandner et al., 2008) also interact with TMV
MP. Most of these factors are involved in TMV cell-to-cell movement.Rubisco catalyzes the first step of CO2 assimilation in photosynthesis and photorespiration. The Rubisco holoenzyme is a heteropolymer consisting of eight large subunits (RbCLs) and eight small subunits (RbCSs). RbCL was reported to interact with the coat protein of Potato virus Y (Feki et al., 2005). Both RbCS and RbCL were reported to interact with the P3 proteins encoded by several potyviruses, including Shallot yellow stripe virus, Onion yellow dwarf virus, Soybean mosaic virus, and Turnip mosaic virus (Lin et al., 2011). Proteomic analysis of the plant-virus interactome revealed that RbCS participates in the formation of virus complexes of Rice yellow mottle virus (Brizard et al., 2006). However, the biological function of Rubisco in viral infection remains unknown.In this study, we show that RbCS plays an essential role in virus movement, host susceptibility, and Tm-22-mediated extreme resistance in the ToMV-host plant interaction. 相似文献
79.
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
80.
Dorscheid DR Wojcik KR Yule K White SR 《American journal of physiology. Lung cellular and molecular physiology》2001,281(4):L982-L992
Our laboratory recently demonstrated the pattern of cell surface glycosylation of nonsecretory central airway epithelium (Dorscheid DR, Conforti AE, Hamann KJ, Rabe KF, and White SR. Histochem J 31: 145-151, 1999), but the role of glycosylation in airway epithelial cell migration and repair is unknown. We examined the functional role of cell surface carbohydrates in wound repair after mechanical injury of 1HAEo(-) human airway epithelial and primary bronchial epithelial monolayers. Wound repair stimulated by epidermal growth factor was substantially attenuated by 10(-7) M tunicamycin (TM), an N-glycosylation inhibitor, but not by the inhibitors deoxymannojirimycin or castanospermine. Wound repair of 1HAEo(-) and primary airway epithelial cells was blocked completely by removal of cell surface terminal fucose residues by alpha-fucosidase. Cell adhesion to collagen matrix was prevented by TM but was only reduced ~20% from control values with prior alpha-fucosidase treatment. Cell migration in Blind Well chambers stimulated by epidermal growth factor was blocked by pretreatment with TM but alpha-fucosidase pretreatment produced no difference from control values. These data suggest that cell surface N-glycosylation has a functional role in airway epithelial cell adhesion and migration and that N-glycosylation with terminal fucosylation plays a role in the complex process of repair by coordination of certain cell-cell functions. 相似文献