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排序方式: 共有279条查询结果,搜索用时 23 毫秒
81.
Ganapathy ME Huang W Rajan DP Carter AL Sugawara M Iseki K Leibach FH Ganapathy V 《The Journal of biological chemistry》2000,275(3):1699-1707
Therapeutic use of cephaloridine, a beta-lactam antibiotic, in humans is associated with carnitine deficiency. A potential mechanism for the development of carnitine deficiency is competition between cephaloridine and carnitine for the renal reabsorptive process. OCTN2 is an organic cation/carnitine transporter that is responsible for Na(+)-coupled transport of carnitine in the kidney and other tissues. We investigated the interaction of several beta-lactam antibiotics with OCTN2 using human cell lines that express the transporter constitutively as well as using cloned human and rat OCTN2s expressed heterologously in human cell lines. The beta-lactam antibiotics cephaloridine, cefoselis, cefepime, and cefluprenam were found to inhibit OCTN2-mediated carnitine transport. These antibiotics possess a quaternary nitrogen as does carnitine. Several other beta-lactam antibiotics that do not possess this structural feature did not interact with OCTN2. The interaction of cephaloridine with OCTN2 is competitive with respect to carnitine. Interestingly, many of the beta-lactam antibiotics that were not recognized by OCTN2 were good substrates for the H(+)-coupled peptide transporters PEPT1 and PEPT2. In contrast, cephaloridine, cefoselis, cefepime, and cefluprenam, which were recognized by OCTN2, did not interact with PEPT1 and PEPT2. The interaction of cephaloridine with OCTN2 was Na(+)-dependent, whereas the interaction of cefoselis and cefepime with OCTN2 was largely Na(+)-independent. Furthermore, the Na(+)-dependent, OCTN2-mediated cellular uptake of cephaloridine could be demonstrated by direct uptake measurements. These studies show that OCTN2 plays a crucial role in the pharmacokinetics and therapeutic efficacy of certain beta-lactam antibiotics such as cephaloridine and that cephaloridine-induced carnitine deficiency is likely to be due to inhibition of carnitine reabsorption in the kidney. 相似文献
82.
Proteomic analysis of soybean root hairs after infection by Bradyrhizobium japonicum 总被引:1,自引:0,他引:1
Wan J Torres M Ganapathy A Thelen J DaGue BB Mooney B Xu D Stacey G 《Molecular plant-microbe interactions : MPMI》2005,18(5):458-467
Infection of soybean root hairs by Bradyrhizobium japonicum is the first of several complex events leading to nodulation. In the current proteomic study, soybean root hairs after inoculation with B. japonicum were separated from roots. Total proteins were analyzed by two-dimensional (2-D) polyacrylamide gel electrophoresis. In one experiment, 96 protein spots were analyzed by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to compare protein profiles between uninoculated roots and root hairs. Another 37 spots, derived from inoculated root hairs over different timepoints, were also analyzed by tandem MS (MS/MS). As expected, some proteins were differentially expressed in root hairs compared with roots (e.g., a chitinase and phosphoenolpyruvate carboxylase). Out of 37 spots analyzed by MS/MS, 27 candidate proteins were identified by database comparisons. These included several proteins known to respond to rhizobial inoculation (e.g., peroxidase and phenylalanine-ammonia lyase). However, novel proteins were also identified (e.g., phospholipase D and phosphoglucomutase). This research establishes an excellent system for the study of root-hair infection by rhizobia and, in a more general sense, the functional genomics of a single, plant cell type. The results obtained also indicate that proteomic studies with soybean, lacking a complete genome sequence, are practical. 相似文献
83.
In human breast cancer MCF 7 cells, the effect of exogenous histone H1 on intracellular calcium ([Ca2+]i) levels was measured using Fura 2AM. The dose and time dependent assessment revealed significant cell killing effect of histone H1 on MCF 7 cells. Histone H1 induced a sustained concentration dependent increase in [Ca2+]i levels in the presence of calcium in the medium, but the increase was reduced in the absence of extra cellular calcium. The effect of histone H1 on intracellular calcium flux measured using 45Ca radiolabel revealed significant inhibition of calcium uptake in endoplasmic reticulum, whereas the rate of uptake was unaltered in the mitochondria. The activities of phospholipase A2 showed a significant transient increase at 1 minute which by the end of 5 minutes decreased, whereas the activities of phospholipase C which showed a transient increase at the end of 1 minute, was maintained at basal levels in histone H1 treated cells compared to control cells. These findings suggest that histone H1 increases [Ca2+]i in MCF 7 cells by stimulating both extra cellular calcium influx and intracellular calcium release at higher concentrations exhibiting cytotoxic effect. 相似文献
84.
Jiang G Zhuang L Miyauchi S Miyake K Fei YJ Ganapathy V 《The Journal of biological chemistry》2005,280(3):2065-2077
GABA functions as an inhibitory neurotransmitter in body muscles and as an excitatory neurotransmitter in enteric muscles in Caenorhabditis elegans. Whereas many of the components of the GABA-ergic neurotransmission in this organism have been identified at the molecular and functional levels, no transporter specific for this neurotransmitter has been identified to date. Here we report on the cloning and functional characterization of a GABA transporter from C. elegans (ceGAT-1) and on the functional relevance of the transporter to the biology of body muscles and enteric muscles. ceGAT-1 is coded by snf-11 gene, a member of the sodium-dependent neurotransmitter symporter gene family in C. elegans. The cloned ceGAT-1 functions as a Na(+)/Cl(-)-coupled high-affinity transporter selective for GABA with a K(t) of approximately 15 microm. The Na(+):Cl(-):GABA stoichiometry for ceGAT-1-mediated transport process is 2:1:1. The transport process is electrogenic as evidenced from GABA-induced inward currents in Xenopus laevis oocytes that express ceGAT-1 heterologously. The transporter is expressed exclusively in GABA-ergic neurons and in two other additional neurons. We also investigated the functional relevance of ceGAT-1 to the biology of body muscles and enteric muscles by ceGAT-1-specific RNA interference (RNAi) in rrf-3 mutant, a strain of C. elegans in which neurons are not refractory to RNAi as in the wild type strain. The down-regulation of ceGAT-1 by RNAi leads to an interesting phenotype associated with altered function of body muscles (as evident from changes in thrashing frequency) and enteric muscles (as evident from the rates of defecation failure) and also with altered sensitivity to aldicarb-induced paralysis. These findings provide unequivocal evidence for a modulatory role of GABA and ceGAT-1 in the biology of cholinergic neurons and in the function of body muscles and enteric muscles in this organism. 相似文献
85.
A systematic proteomic study of seed filling in soybean. Establishment of high-resolution two-dimensional reference maps, expression profiles, and an interactive proteome database 总被引:7,自引:0,他引:7 下载免费PDF全文
A high-throughput proteomic approach was employed to determine the expression profile and identity of hundreds of proteins during seed filling in soybean (Glycine max) cv Maverick. Soybean seed proteins were analyzed at 2, 3, 4, 5, and 6 weeks after flowering using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. This led to the establishment of high-resolution proteome reference maps, expression profiles of 679 spots, and corresponding matrix-assisted laser desorption ionization time-of-flight mass spectrometry spectra for each spot. Database searching with these spectra resulted in the identification of 422 proteins representing 216 nonredundant proteins. These proteins were classified into 14 major functional categories. Proteins involved in metabolism, protein destination and storage, metabolite transport, and disease/defense were the most abundant. For each functional category, a composite expression profile is presented to gain insight into legume seed physiology and the general regulation of proteins associated with each functional class. Using this approach, an overall decrease in metabolism-related proteins versus an increase in proteins associated with destination and storage was observed during seed filling. The accumulation of unknown proteins, sucrose transport and cleavage enzymes, cysteine and methionine biosynthesis enzymes, 14-3-3-like proteins, lipoxygenases, storage proteins, and allergenic proteins during seed filling is also discussed. A user-intuitive database (http://oilseedproteomics.missouri.edu) was developed to access these data for soybean and other oilseeds currently being investigated. 相似文献
86.
The adaptive regulation of amino acid transport system A is associated to changes in ATA2 expression 总被引:6,自引:0,他引:6
Gazzola RF Sala R Bussolati O Visigalli R Dall'Asta V Ganapathy V Gazzola GC 《FEBS letters》2001,490(1-2):11-14
The activity of transport system A for neutral amino acids is adaptively stimulated upon amino acid starvation. In cultured human fibroblasts this treatment causes an increase in the expression of the ATA2 system A transporter gene. ATA2 mRNA increase and transport stimulation are suppressed by system A substrates, but they are unaffected by other amino acids. Supplementation of amino acid-starved cells with substrates of system A causes a decrease in both ATA2 mRNA and system A transport activity. These results suggest a direct relationship between ATA2 expression and system A transport activity. 相似文献
87.
A comparison of caveolae and caveolin-1 to folate receptor alpha in retina and retinal pigment epithelium 总被引:1,自引:0,他引:1
Bridges CC El-Sherbeny A Roon P Ola MS Kekuda R Ganapathy V Camero RS Cameron PL Smith SB 《The Histochemical journal》2001,33(3):149-158
Caveolae are flask-shaped membrane invaginations present in most mammalian cells. They are distinguished by the presence of a striated coat composed of the protein, caveolin. Caveolae have been implicated in numerous cellular processes, including potocytosis in which caveolae are hypothesized to co-localize with folate receptor and participate in folate uptake. Our laboratory has recently localized folate receptor to the basolateral surface of the retinal pigment epithelium (RPE). It is present also in many other cells of the retina. In the present study, we asked whether caveolae were present in the RPE, and if so, whether their pattern of distribution was similar to folate receptor . We also examined the distribution pattern of caveolin-1, which can be a marker of caveolae. Extensive electron microscopical analysis revealed caveolae associated with endothelial cells. However, none were detected in intact or cultured RPE. Laser scanning confocal microscopical analysis of intact RPE localized caveolin-1 to the apical and basal surfaces, a distribution unlike folate receptor . Western analysis confirmed the presence of caveolin-1 in cultured RPE cells and laser scanning confocal microscopy localized the protein to the basal plasma membrane of the RPE, a distribution like that of folate receptor . This distribution was confirmed by electron microscopic immunolocalization. The lack of caveolae in the RPE suggests that these structures may not be essential for folate internalization in the RPE. 相似文献
88.
Intraoperative Fluid Restriction in Pancreatic Surgery: A Double Blinded Randomised Controlled Trial
Ganapathy van Samkar Wietse J. Eshuis Roelof J. Bennink Thomas M. van Gulik Marcel G. W. Dijkgraaf Benedikt Preckel Stefan de Hert Dirk J. Gouma Markus W. Hollmann Olivier R. C. Busch 《PloS one》2015,10(10)
Background
Perioperative fluid restriction in a variety of operations has shown improvement of: complications, recovery of gastrointestinal function and length of stay (LOS). We investigated effects of crystalloid fluid restriction in pancreatic surgery. Our hypothesis: enhanced recovery of gastrointestinal function.Methods
In this double-blinded randomized trial, patients scheduled to undergo pancreatoduodenectomy (PD) were randomized: standard (S:10ml/kg/hr) or restricted (R:5ml/kg/hr) fluid protocols. Primary endpoint: gastric emptying scintigraphically assessed on postoperative day 7.Results
In 66 randomized patients, complications and 6-year survival were analyzed. 54 patients were analyzed in intention to treat: 24 S-group and 30 R-group. 32 patients actually underwent a PD and 16 patients had a palliative gastrojejunostomy bypass operation in the full protocol analysis. The median gastric emptying time (T½) was 104 minutes (S-group, 95% confidence interval: 74–369) versus 159 minutes (R-group, 95% confidence interval: 61–204) (P = 0.893, NS). Delayed gastric emptying occurred in 10 patients in the S-group and in 13 patients in the R-group (45% and 50%, P = 0.779, NS). The primary outcome parameter, gastric emptying time, did not show a statistically significant difference between groups.Conclusion
A fluid regimen of 10ml/kg/hr or 5ml/kg/hr during pancreatic surgery did not lead to statistically significant differences in gastric emptying. A larger study would be needed to draw definite conclusions about fluid restriction in pancreatic surgery.Trial registration
ISRCTN62621488 相似文献89.
Globally, one of the major technologic goals is to achieve cost-effective lignocellulosic ethanol production from biomass feedstocks. Lignocellulosic biomass of four dedicated energy crops [giant reed (Arundo donax L.), elephantgrass (Pennisetum purpureum (Schumach), Miscanthus × giganteus (Illinois clone), and (clone Q42641) {hybrid of Miscanthus sinensis Anderss. and Miscanthus sacchariflorus (Maxim)}, Hack. called giant miscanthus, and sugarcane clone US 84-1028 (Saccharum L. spp. hybrid)] and residues from two crops [soybean (Glycine max (L.) Merr.) litter and rice (Oryza sativa L.) husk] were tested for bioethanol production using cellulose solvent-based lignocellulose fractionation (CSLF) pretreatment and enzymatic (cellulase) hydrolysis. Giant miscanthus (Illinois), giant reed, giant miscanthus (Q42641), elephantgrass, and sugarcane all yielded higher amount of glucose on a biomass dry weight basis (0.290-0.331 g/g), than did rice husk (0.181 g/g) and soybean litter (0.186 g/g). To reduce the capital investment for energy consumption in fermentation, we used a self-flocculating yeast strain (SPSC01) to ferment the lignocellulosic biomass hydrolysates. Bioethanol production was ~0.1 g/g in dedicated energy crops and less in two crop residues. These methods and data can help to develop a cost-effective downstream process for bioethanol production. 相似文献
90.
Thomas B Suhadev M Mani J Ganapathy BG Armugam A Faizunnisha F Chelliah M Wares F 《PloS one》2011,6(11):e27752