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排序方式: 共有153条查询结果,搜索用时 692 毫秒
61.
Marija K. Massey Michael J. Reiterman Jad Mourad Douglas B. Luckie 《Biochemistry and Biophysics Reports》2021
The disease, cystic fibrosis, is caused by the malfunction of the cystic fibrosis transmembrane conductance regulator. Expression of functional CFTR may normally regulate extracellular pH via control of bicarbonate efflux. Reports also suggest that the CFTR may be a Cl-/HCO3- exchanger. If true, this could be very important for treatment of CF given the airway host defense system is quite sensitive to pH, and acidic pH been found to increase mucus viscosity. We compared evidentiary support of four possible models of CFTR's role in the transport of bicarbonate: 1) CFTR as a Cl-channel that permits bicarbonate conductance, 2) CFTR as an anion Cl-/HCO3- exchanger (AE), 3.) CFTR as both a Cl-channel and an AE, and 4.) CFTR as a Cl-channel that allows for transport of bicarbonate and regulates an independent AE. The effect of stimulators and inhibitors of CFTR and AEs were evaluated via iodide efflux and studies of extracellular pH. This data, as well as that published by others, suggest that while CFTR may support and regulate bicarbonate flux it is unlikely it directly performs Cl-/HCO3- anion exchange. 相似文献
62.
Chaobin Jin Rawaf Alenazy Yinhu Wang Rumana Mowla Yinhui Qin Jin Quan Eugene Tan Natansh Deepak Modi Xinjie Gu Steven W. Polyak Henrietta Venter Shutao Ma 《Bioorganic & medicinal chemistry letters》2019,29(7):882-889
A series of novel 5-methoxy-2,3-naphthalimide derivatives were designed, synthesized and evaluated for their biological activities. In particular, the ability of the compounds to synergize with antimicrobials, to inhibit Nile Red efflux, and to target AcrB was assayed. The results showed that the most of the tested compounds more sensitized the Escherichia coli BW25113 to the antibiotics than the parent compounds 7c and 15, which were able to inhibit Nile Red efflux. Significantly, compound A5 possessed the most potent antibacterial synergizing activity in combination with levofloxacin by 4 times and 16 times at the concentration of 8 and 16?µg/mL, respectively, whilst A5 could effectively abolish Nile Red efflux at 100?μM. Additionally, target effect of A5 was confirmed in the outer- or inner membrane permeabilization assays. Therefore, A5 is an excellent lead compound for further structural optimization. 相似文献
63.
Faustino Vidal-Aroca Alexandra Meng Tanja Minz Malcolm G.P. Page Jürg Dreier 《Journal of microbiological methods》2009,79(2):232-237
Multi-drug-resistant bacteria can cause serious infections that are extremely difficult to treat. Bacterial efflux pumps are known to contribute to multi-drug resistance and, thus, constitute a promising target for novel antibacterial agents. Resazurin is widely used to monitor bacterial growth because resazurin is reduced to the fluorescent resorufin by live cells. We have shown by flow cytometric analysis and by accumulation studies with wild type and efflux deficient strains that resazurin is a substrate of efflux pumps in Escherichia coli and Pseudomonas aeruginosa. Our investigations showed that the conversion rate of resazurin to resorufin is affected by efflux pumps. This finding was used to design an assay useful to detect efflux pump activity and to find potential efflux-pump inhibitors in a microtiter plate format. Mefloquine was detected as efflux-pump inhibitor when a panel of selected chemical compounds was tested for assay validation purposes. 相似文献
64.
Poly(ethyleneglycol) (PEG), anchored at the surface of liposomes via the conjugation to a lipid, is commonly used for increasing the liposome stability in the blood stream. In order to gain a better understanding of the protective properties of interfacial polymers, we have studied the binding of melittin to PEG-lipid-containing membranes as well as the melittin-induced efflux of a fluorescent marker from liposomes containing PEG-lipids. We examined the effect of the polymer size by using PEG with molecular weights of 2000 and 5000. In addition, we studied the role of the anchoring lipid by comparing PEG conjugated to phosphatidylethanolamine (PE) which results in a negatively charged PEG-PE, with PEG conjugated to ceramide (Cer) which provides the neutral PEG-Cer. Our results show that interfacial PEG does not prevent melittin adsorption onto the interface. In fact, PEG-PE promotes melittin binding, most likely because of attractive electrostatic interactions with the negative interfacial charge density of the PEG-PE-containing liposomes. However, PEG-lipids limit the lytic potential of melittin. The phenomenon is proposed to be associated with the change in the polymorphic tendencies of the liposome bilayers. The present findings reveal that the protective effect associated with interfacial hydrophilic polymers is not universal. Molecules like melittin can sense surface charges borne by PEG-lipids, and the influence of PEG-lipids on liposomal properties such as the polymorphic propensities may be involved in the so-called protective effect. 相似文献
65.
目的:探讨鲍曼不动杆菌耐药程度与其主动外排泵蛋白的相关性。方法:首先用纸片扩散法检测64株临床鲍曼不动杆菌对8种抗菌药物的敏感性;将其分为A组(0~2种抗生素耐药)、B组(对3~5种抗生素耐药)和C组(对6~8种抗生素耐药);检测64株临床鲍曼不动杆菌对罗丹明6G的外排情况,筛选出罗丹明6G外排明显增加的菌株;并用逆转录-聚合酶链反应(RT-PCR)方法检测主动外排泵基因AdeABC的表达水平。结果:64株鲍曼不动杆菌中有4株对0~2种抗生素耐药(A组),对3~5种抗生素耐药的有33株(B组),对6~8种抗生素耐药的有27株(C组);多重耐药组鲍曼不动杆菌罗丹6G外排明显增高,外排程度A组相似文献
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68.
Although the neurotoxic tryptophan-kynurenine pathway metabolite quinolinic acid originates in brain by both local de novo synthesis and entry from blood, its concentrations in brain parenchyma, extracellular fluid, and CSF are normally below blood values. In the present study, an intraperitoneal injection of probenecid (400 mg/kg), an established inhibitor of acid metabolite transport in brain, into gerbils, increased quinolinic acid concentrations in striatal homogenates, CSF, serum, and homogenates of kidney and liver. Direct administration of probenecid (10 mM) into the brain compartment via an in vivo microdialysis probe implanted into the striatum also caused a progressive elevation in both quinolinic acid and homovanillic acid concentrations in the extracellular fluid compartment but was without effect on serum quinolinic acid levels. A model of microdialysis transport showed that the elevations in extracellular fluid quinolinic acid and homovanillic acid levels following intrastriatal application are consistent with probenecid block of a microvascular acid transport mechanism. We conclude that quinolinic acid in brain is maintained at concentrations below blood levels largely by active extrusion via a probenecid-sensitive carrier system. 相似文献
69.
The substrate specificity of tripartite efflux systems of Pseudomonas aeruginosa is determined by the RND component 总被引:1,自引:0,他引:1
Murata T Kuwagaki M Shin T Gotoh N Nishino T 《Biochemical and biophysical research communications》2002,299(2):247-251
The tripartite efflux systems MexAB-OprM and MexCD-OprJ of Pseudomonas aeruginosa each display characteristic substrate specificity against a variety of antimicrobial agents. The chimeric efflux system MexC-MexB-OprJ/DeltaMexD constructed by exchange of MexD with MexB endowed the recombinant host the same resistance profile as MexAB-OprM rather than MexCD-OprJ. The change of substrate specificity was shown to be due to extrusion from the chimeric efflux system by cellular accumulation experiments using tetracycline, erythromycin, and ethidium bromide. Thus, we conclude that MexB and MexD are primary components of the efflux system responsible for sorting extrusion substrates. 相似文献
70.
Xu XH Wan Q Kyriacou SV Brownlow WJ Nowak ME 《Biochemical and biophysical research communications》2003,305(4):941-949
The resistance mechanism in three strains of Pseudomonas aeruginosa, Delta ABM (devoid of MexAB-OprM), WT, and nalB-1 (overexpression of MexAB-OprM), was investigated using real-time single live cell imaging and fluorescence spectroscopy. Time courses of fluorescence intensity of these three strains in ethidium bromide (EtBr) showed that accumulation kinetics and extrusion machinery were highly dependent upon pump substrate (EtBr) concentration. At high substrate concentration (100 microM), the accumulation kinetic profiles in the cells at earlier incubation times were similar to those observed in low concentration. As EtBr accumulated in the cells reached a critical concentration, the fluorescence intensity of Delta ABM decreased below the fluorescence intensity of EtBr in buffer solution. This result suggested an inductive mechanism in the development of substrate resistance in P. aeruginosa. Substrates appeared to trigger the degradation of EtBr in Delta ABM. Unlike bulk measurements, single live cell imaging overcame the ensemble measurement of bulk analysis and showed that efflux machinery and resistance mechanism in individual cells were not synchronized. 相似文献