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61.
Cadmium retention in rice roots is influenced by cadmium availability, chelation and translocation 总被引:13,自引:0,他引:13
Analysis of rice plants exposed to a broad range of relatively low and environmentally realistic Cd concentrations showed that the root capacity to retain Cd ions rose from 49 to 79%, corresponding to increases in the external Cd2+ concentration in the 0.01-1 μM range. Fractioning of Cd ions retained by roots revealed that different events along the metal sequestration pathway (i.e. chelation by thiols, vacuolar compartmentalization, adsorption) contributed to Cd immobilization in the roots. However, large amounts of Cd ions (around 24% of the total amount) predictable as potentially mobile were still found in all conditions, while the amount of Cd ions loaded in the xylem seemed to have already reached saturation at 0.1 μM Cd2+, suggesting that Cd translocation may also play an indirect role in determining Cd root retention, especially at the highest external concentrations. In silico search and preliminary analyses in yeast suggest OsHMA2 as a good candidate for the control of Cd xylem loading in rice. Taken as a whole, data indicate Cd chelation, compartmentalization, adsorption and translocation processes as components of a complex 'firewall system' which acts in limiting Cd translocation from the root to the shoot and which reaches different equilibrium positions depending on Cd external concentration. 相似文献
62.
Cadherins are Ca2+-dependent cell adhesion molecules that play fundamental roles in animal development and homeostasis. A number of cadherins contain conserved binding sites for catenins in their cytoplasmic region that are important for the adhesive function of these cadherins by mediating their interaction to the cytoskeleton. However, most cadherins lack apparent binding sites for catenins and their cytoplasmic interacting partners are mostly unknown. In this paper, we show, using bioinformatics, that a number of insect and vertebrate cadherins lacking catenin-binding sites contain conserved consensus sequences for C-terminal PSD-95/Discs-large/ZO-1 (PDZ)-domain-binding sites. This suggests that PDZ-domain-containing proteins are common cytoplasmic interacting partners for cadherins lacking catenin-binding sites.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorized users. 相似文献
63.
Solano AF Leipnitz G De Bortoli GM Seminotti B Amaral AU Fernandes CG Latini AS Dutra-Filho CS Wajner M 《Free radical research》2008,42(8):707-715
The present work investigated the in vitro effects of isovaleric acid (IVA) and isovalerylglycine (IVG), which accumulate in isovaleric acidemia (IVAcidemia), on important parameters of oxidative stress in supernatants and mitochondrial preparations from brain of 30-day-old rats. IVG, but not IVA, significantly increased TBA-RS and chemiluminescence values in cortical supernatants. Furthermore, the addition of free radical scavengers fully prevented IVG-induced increase of TBA-RS. IVG also decreased GSH concentrations, whereas IVA did not modify this parameter in brain supernatants. Furthermore, IVG did not alter lipid peroxidation or GSH concentrations in mitochondrial preparations, indicating that the generation of oxidants by IVG was dependent on cytosolic mechanisms. On the other hand, IVA significantly induced carbonyl formation both in supernatants and purified mitochondrial preparations from rat brain, with no effect observed for IVG. Therefore, it is presumed that oxidative damage may be at least in part involved in the pathophysiology of the neuropathology of IVAcidemia. 相似文献
64.
Giuseppina Mattace Raso Claudio Pirozzi Roberta d'Emmanuele di Villa Bianca Raffaele Simeoli Anna Santoro Adriano Lama Francesca Di Guida Roberto Russo Carmen De Caro Raffaella Sorrentino Antonio Calignano Rosaria Meli 《PloS one》2015,10(5)
Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF), and renin angiotensin system (RAS) modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day) for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the activation of angiotensin receptor 1 underlying pathways in mesenteric beds was shown in basal conditions in PEA-treated SHR. In conclusion, our data demonstrate the involvement of epoxyeicosatrienoic acids and renin angiotensin system in the blood pressure lowering effect of PEA. 相似文献
65.
Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC). This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients’ genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28) has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite) to SN-38 glucuronide (SN-38G) leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients’ plasma, we developed and validated a new, sensitive and specific HPLC–MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm) using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R2 ≥0.9962) over the concentration ranges (10–10000 ng/mL for irinotecan, 1–500 ng/mL for SN-38 and SN-38G and 1–5000 ng/mL for APC) and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to a pharmacokinetic study in metastatic CRC patients enrolled in a genotype-guided phase Ib study of irinotecan administered in combination with 5-fluorouracil/leucovorin and bevacizumab. 相似文献
66.
Bianca Schmid Melanie Rinas Alessia Ruggieri Eliana Gisela Acosta Marie Bartenschlager Antje Reuter Wolfgang Fischl Nathalie Harder Jan-Philip Bergeest Michael Flossdorf Karl Rohr Thomas H?fer Ralf Bartenschlager 《PLoS pathogens》2015,11(12)
Dengue virus (DENV) is the most common mosquito-transmitted virus infecting ~390 million people worldwide. In spite of this high medical relevance, neither a vaccine nor antiviral therapy is currently available. DENV elicits a strong interferon (IFN) response in infected cells, but at the same time actively counteracts IFN production and signaling. Although the kinetics of activation of this innate antiviral defense and the timing of viral counteraction critically determine the magnitude of infection and thus disease, quantitative and kinetic analyses are lacking and it remains poorly understood how DENV spreads in IFN-competent cell systems. To dissect the dynamics of replication versus antiviral defense at the single cell level, we generated a fully viable reporter DENV and host cells with authentic reporters for IFN-stimulated antiviral genes. We find that IFN controls DENV infection in a kinetically determined manner that at the single cell level is highly heterogeneous and stochastic. Even at high-dose, IFN does not fully protect all cells in the culture and, therefore, viral spread occurs even in the face of antiviral protection of naïve cells by IFN. By contrast, a vaccine candidate DENV mutant, which lacks 2’-O-methylation of viral RNA is profoundly attenuated in IFN-competent cells. Through mathematical modeling of time-resolved data and validation experiments we show that the primary determinant for attenuation is the accelerated kinetics of IFN production. This rapid induction triggered by mutant DENV precedes establishment of IFN-resistance in infected cells, thus causing a massive reduction of virus production rate. In contrast, accelerated protection of naïve cells by paracrine IFN action has negligible impact. In conclusion, these results show that attenuation of the 2’-O-methylation DENV mutant is primarily determined by kinetics of autocrine IFN action on infected cells. 相似文献
67.
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69.
Carmen Bednorz Sebastian Guenther Kathrin Oelgeschl?ger Bianca Kinnemann Robert Pieper Susanne Hartmann Karsten Tedin Torsten Semmler Konrad Neumann Peter Schierack Astrid Bethe Lothar H. Wieler 《Applied and environmental microbiology》2013,79(24):7896-7904
Feed supplementation with the probiotic Enterococcus faecium for piglets has been found to reduce pathogenic gut microorganisms. Since Escherichia coli is among the most important pathogens in pig production, we performed comprehensive analyses to gain further insight into the influence of E. faecium NCIMB 10415 on porcine intestinal E. coli. A total of 1,436 E. coli strains were isolated from three intestinal habitats (mucosa, digesta, and feces) of probiotic-supplemented and nonsupplemented (control) piglets. E. coli bacteria were characterized via pulsed-field gel electrophoresis (PFGE) for clonal analysis. The high diversity of E. coli was reflected by 168 clones. Multilocus sequence typing (MLST) was used to determine the phylogenetic backgrounds, revealing 79 sequence types (STs). Pathotypes of E. coli were further defined using multiplex PCR for virulence-associated genes. While these analyses discerned only a few significant differences in the E. coli population between the feeding groups, analyses distinguishing clones that were uniquely isolated in either the probiotic group only, the control group only, or both groups (shared group) revealed clear effects at the habitat level. Interestingly, extraintestinal pathogenic E. coli (ExPEC)-typical clones adhering to the mucosa were significantly reduced in the probiotic group. Our data show a minor influence of E. faecium on the overall population of E. coli in healthy piglets. In contrast, this probiotic has a profound effect on mucosa-adherent E. coli. This finding further substantiates a specific effect of E. faecium strain NCIMB 10415 in piglets against pathogenic E. coli in the intestine. In addition, these data question the relevance of data based on sampling fecal E. coli only. 相似文献
70.
Carolina G. Fernandes Guilhian Leipnitz Bianca Seminotti Alexandre U. Amaral Ângela Zanatta Carmen R. Vargas Carlos S. Dutra Filho Moacir Wajner 《Cellular and molecular neurobiology》2010,30(2):317-326
High levels of phenylalanine (Phe) are the biochemical hallmark of phenylketonuria (PKU), a neurometabolic disorder clinically
characterized by severe mental retardation and other brain abnormalities, including cortical atrophy and microcephaly. Considering
that the pathomechanisms leading to brain damage and particularly the marked cognitive impairment in this disease are poorly
understood, in the present study we investigated the in vitro effect of Phe, at similar concentrations as to those found in
brain of PKU patients, on important parameters of oxidative stress in the hippocampus and cerebral cortex of developing rats.
We found that Phe induced in vitro lipid peroxidation (increase of TBA-RS values) and protein oxidative damage (sulfhydryl
oxidation) in both cerebral structures. Furthermore, these effects were probably mediated by reactive oxygen species, since
the lipid oxidative damage was totally prevented by the free radical scavengers α-tocopherol and melatonin, but not by L-NAME,
a potent inhibitor of nitric oxide synthase. Accordingly, Phe did not induce nitric oxide synthesis, but significantly decreased
the levels of reduced glutathione (GSH), the major brain antioxidant defense, in hippocampus and cerebral cortex supernatants.
Phe also reduced the thiol groups of a commercial GSH solution in a cell-free medium. We also found that the major metabolites
of Phe catabolism, phenylpyruvate, phenyllactate and phenylacetate also increased TBA-RS levels in cerebral cortex, but to
a lesser degree. The data indicate that Phe elicits oxidative stress in the hippocampus, a structure mainly involved with
learning/memory, and also in the cerebral cortex, which is severely damaged in PKU patients. It is therefore presumed that
this pathomechanism may be involved at least in part in the severe cognitive deficit and in the characteristic cortical atrophy
associated with dysmyelination and leukodystrophy observed in this disorder. 相似文献