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71.
Activation of glucose transport during simulated ischemia in H9c2 cardiac myoblasts is mediated by protein kinase C isoforms 总被引:1,自引:0,他引:1
Agnetti G Maraldi T Fiorentini D Giordano E Prata C Hakim G Muscari C Guarnieri C Caldarera CM 《Life sciences》2005,78(3):264-270
Glucose transport into cells may be regulated by a variety of conditions, including ischemia. We investigated whether some enzymes frequently involved in the metabolic adaptation to ischemia are also required for glucose transport activation. Ischemia was simulated by incubating during 3 h H9c2 cardiomyoblasts in a serum- and glucose-free medium in hypoxia. Under these conditions 2-deoxy-d-[2,6-3H]-glucose uptake was increased (57% above control levels, p < 0.0001) consistently with GLUT1 and GLUT4 translocation to sarcolemma. Tyrosine kinases inhibition via tyrphostin had no effect on glucose transport up-regulation induced by simulated ischemia. On the other hand, chelerythrine, a broad range inhibitor of protein kinase C isoforms, and rottlerin, an inhibitor of protein kinase C delta, completely prevented the stimulation of the transport rate. A lower activation of hexose uptake (19%, p < 0.001) followed also treatment with Gö6976, an inhibitor of conventional protein kinases C. Finally, PD98059-mediated inhibition of the phosphorylation of ERK 1/2, a downstream mitogen-activated protein kinase (MAPK), only partially reduced the activation of glucose transport induced by simulated ischemia (31%, p < 0.01), while SB203580, an inhibitor of p38 MAPK, did not exert any effect. These results indicate that stimulation of protein kinase C delta is strongly related to the up-regulation of glucose transport induced by simulated ischemia in cultured cardiomyoblasts and that conventional protein kinases C and ERK 1/2 are partially involved in the signalling pathways mediating this process. 相似文献
72.
Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis 总被引:3,自引:0,他引:3
Two-component signal transduction systems, comprised of histidine kinases and their response regulator substrates, are the predominant means by which bacteria sense and respond to extracellular signals. These systems allow cells to adapt to prevailing conditions by modifying cellular physiology, including initiating programs of gene expression, catalyzing reactions, or modifying protein–protein interactions. These signaling pathways have also been demonstrated to play a role in coordinating bacterial cell cycle progression and development. Here we report a system-level investigation of two-component pathways in the model organism Caulobacter crescentus . First, by a comprehensive deletion analysis we show that at least 39 of the 106 two-component genes are required for cell cycle progression, growth, or morphogenesis. These include nine genes essential for growth or viability of the organism. We then use a systematic biochemical approach, called phosphotransfer profiling, to map the connectivity of histidine kinases and response regulators. Combining these genetic and biochemical approaches, we identify a new, highly conserved essential signaling pathway from the histidine kinase CenK to the response regulator CenR, which plays a critical role in controlling cell envelope biogenesis and structure. Depletion of either cenK or cenR leads to an unusual, severe blebbing of cell envelope material, whereas constitutive activation of the pathway compromises cell envelope integrity, resulting in cell lysis and death. We propose that the CenK–CenR pathway may be a suitable target for new antibiotic development, given previous successes in targeting the bacterial cell wall. Finally, the ability of our in vitro phosphotransfer profiling method to identify signaling pathways that operate in vivo takes advantage of an observation that histidine kinases are endowed with a global kinetic preference for their cognate response regulators. We propose that this system-wide selectivity insulates two-component pathways from one another, preventing unwanted cross-talk. 相似文献
73.
D'Angelo A Geroldi D Hancock MA Valtulina V Cornaglia AI Spencer CA Emanuele E Calligaro A Koschinsky ML Speziale P Visai L 《Biochimica et biophysica acta》2005,1687(1-3):1-10
Lipoprotein(a) [Lp(a)] entrapment by vascular extracellular matrix may be important in atherogenesis. We sought to determine whether laminin, a major component of the basal membrane, may contribute to Lp(a) retention in the arterial wall. First, immunohistochemistry experiments were performed to examine the relative distribution of Lp(a) and laminin in human carotid artery specimens. There was a high degree of co-localization of Lp(a) and laminin in atherosclerotic specimens, but not in non-atherosclerotic sections. We then studied the binding interaction between Lp(a) and laminin in vitro. ELISA experiments showed that native Lp(a) particles and 17K and 12K recombinant apolipoprotein(a) [r-apo(a)] variants interacted strongly with laminin whereas LDL, apoB-100, and the truncated KIV(6-P), KIV(8-P), and KIV(9-P) r-apo(a) variants did not. Overall, the ELISA data demonstrated that Lp(a) binding to laminin is mediated by apo(a) and a combination of the lysine analogue epsilon-aminocaproic acid and salt effectively decreases apo(a) binding to laminin. Secondary binding analyses with 125I-labeled r-apo(a) revealed equilibrium dissociation constants (K(d)) of 180 and 360 nM for the 17K and 12K variants binding to laminin, respectively. Such similar K(d) values between these two r-apo(a) variants suggest that isoform size does not appear to influence apo(a) binding to laminin. In summary, our data suggest that laminin may bind to apo(a) in the atherosclerotic intima, thus contributing to the selective retention of Lp(a) in this milieu. 相似文献
74.
NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome 总被引:7,自引:0,他引:7
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De Luca A Bottillo I Sarkozy A Carta C Neri C Bellacchio E Schirinzi A Conti E Zampino G Battaglia A Majore S Rinaldi MM Carella M Marino B Pizzuti A Digilio MC Tartaglia M Dallapiccola B 《American journal of human genetics》2005,77(6):1092-1101
Neurofibromatosis type 1 (NF1) demonstrates phenotypic overlap with Noonan syndrome (NS) in some patients, which results in the so-called neurofibromatosis-Noonan syndrome (NFNS). From a genetic point of view, NFNS is a poorly understood condition, and controversy remains as to whether it represents a variable manifestation of either NF1 or NS or is a distinct clinical entity. To answer this question, we screened a cohort with clinically well-characterized NFNS for mutations in the entire coding sequence of the NF1 and PTPN11 genes. Heterozygous NF1 defects were identified in 16 of the 17 unrelated subjects included in the study, which provides evidence that mutations in NF1 represent the major molecular event underlying this condition. Lesions included nonsense mutations, out-of-frame deletions, missense changes, small inframe deletions, and one large multiexon deletion. Remarkably, a high prevalence of inframe defects affecting exons 24 and 25, which encode a portion of the GAP-related domain of the protein, was observed. On the other hand, no defect in PTPN11 was observed, and no lesion affecting exons 11-27 of the NF1 gene was identified in 100 PTPN11 mutation-negative subjects with NS, which provides further evidence that NFNS and NS are genetically distinct disorders. These results support the view that NFNS represents a variant of NF1 and is caused by mutations of the NF1 gene, some of which have been demonstrated to cause classic NF1 in other individuals. 相似文献
75.
Comparison of the transition states for folding of two Ig-like proteins from different superfamilies
In the "fold approach" proteins with a similar fold but different sequences are compared in order to investigate the relationship between native state structure and folding behaviour. Here we compare the properties of the transition states for folding of TI I27, the 27th immunoglobulin domain from human cardiac titin, and that of TNfn3, the third fibronectin type III domain from human tenascin. Experimental phi-values were used as restraints in molecular dynamics simulations to determine the structures that make up the transition state ensembles (TSEs) for folding of the two proteins. The restrained simulations that we present allow a detailed structural comparison of the two TSEs to be made. Further calculations show explicitly that for both proteins the formation of the interactions involving the residues in the folding nucleus is sufficient for the establishment of the topology of the Ig-like fold. We found that, although the folding nuclei of the two proteins are similar, the packing of the folding nucleus of TI I27 is much tighter than that of TNfn3, reflecting the higher experimental phi-values and beta(T) (Tanford Beta) of TI I27. These results suggest that the folding nucleus can be significantly deformed to accommodate extensive sequence variation while conserving the same folding mechanism. 相似文献
76.
Paroni R Fermo I Molteni L Folini L Pastore MR Mosca A Bosi E 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2006,834(1-2):183-187
Aim of this study was to set up a method by capillary electrophoresis to detect lactulose and mannitol in urine after an oral load, and to estimate the intestinal permeability in controls and in type I diabetes patients. The underivatized carbohydrates were monitored by indirect UV detection using sorbate, cetyltrimethylammonium bromide and LiOH as background electrolyte. Urines were purified by solid phase extraction, shaken with cation exchange resin, filtered and analysed. Carbohydrates migrated in <10 min in relation to their pK(a) and M(r). Controls (n = 33) and patients (n = 23) had an excretion ratio lactulose/mannitol 0.025 (0.018-0.051) and 0.067 (0.050-0.127), respectively (p < 0.01, median, interquartile range). 相似文献
77.
Antonio Porro Michelle Haber Daniel Diolaiti Nunzio Iraci Michelle Henderson Samuele Gherardi Emanuele Valli Marcia A. Munoz Chengyuan Xue Claudia Flemming Manfred Schwab Jason H. Wong Glenn M. Marshall Giuliano Della Valle Murray D. Norris Giovanni Perini 《The Journal of biological chemistry》2010,285(25):19532-19543
78.
Elisa Redaelli Rita Restano Cassulini Deyanira Fuentes Silva Herlinda Clement Emanuele Schiavon Fernando Z. Zamudio George Odell Annarosa Arcangeli Jeffrey J. Clare Alejandro Alag��n Ricardo C. Rodr��guez de la Vega Lourival D. Possani Enzo Wanke 《The Journal of biological chemistry》2010,285(6):4130-4142
79.
80.
Roberto Bertoni Cristiana Callieri Gianluca Corno Serena Rasconi Emanuele Caravati Mario Contesini 《Hydrobiologia》2010,644(1):279-287
We analysed the long-term dynamics (1980–2007) of hypolimnetic and epilimnetic bacterial abundances and organic carbon concentrations,
both dissolved (DOC) and particulate (POC), in the deep holo-oligomictic Lake Maggiore, included in the Southern Alpine Lakes
Long-Term Ecological Research (LTER) site. During the 28 years of investigation, bacterial abundance and POC concentrations
did not decrease with declining phosphorus concentrations, while DOC concentrations showed a pronounced decrease in the epi-
and hypolimnion. We used the annual mean total lake heat content and total annual precipitation as climate-related variables,
and in-lake total phosphorus as a proxy for trophic state. The model (forward stepwise regression, FSR) showed that reduced
anthropogenic pressure was more significant than climate change in driving the trend in DOC concentrations. Bacterial dynamics
in the hypolimnion mirrored the fluctuations observed in the epilimnion, but average cell abundance was three times lower.
The FSR model indicates that bacterial number variability was dependent on POC in the epilimnion and DOC in the hypolimnion.
In the hypolimnion, cell biovolumes for rod and coccal morphotypes were significantly larger than in the epilimnion. 相似文献