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51.
Priyanka Prakash Douglas Litwin Hong Liang Suparna Sarkar-Banerjee Drew Dolino Yong Zhou John F. Hancock Vasanthi Jayaraman Alemayehu A. Gorfe 《Biophysical journal》2019,116(2):179-183
Recent studies have shown that the small GTPase KRAS adopts multiple orientations with respect to the plane of anionic model membranes, whereby either the three C-terminal helices or the three N-terminal β-strands of the catalytic domain face the membrane. This has functional implications because, in the latter, the membrane occludes the effector-interacting surface. However, it remained unclear how membrane reorientation occurs and, critically, whether it occurs in the cell in which KRAS operates as a molecular switch in signaling pathways. Herein, using data from a 20 μs-long atomistic molecular dynamics simulation of the oncogenic G12V-KRAS mutant in a phosphatidylcholine/phosphatidylserine bilayer, we first show that internal conformational fluctuations of flexible regions in KRAS result in three distinct membrane orientations. We then show, using single-molecule fluorescence resonance energy transfer measurements in native lipid nanodiscs derived from baby hamster kidney cells, that G12V-KRAS samples three conformational states that correspond to the predicted orientations. The combined results suggest that relatively small energy barriers separate orientation states and that signaling-competent conformations dominate the overall population. 相似文献
52.
Debapriya De Priyanka Chowdhury Sujogya K. Panda Utpal Ghosh 《Journal of cellular biochemistry》2019,120(12):19841-19857
Despite the advancement of the pharmaceutical industry, medicinal plants are still a reliable source of traditional medicines to cure a number of diseases. Various parts of Dillenia pentagyna are used in traditional medicine in India for treatment of various disorders including cancers, but detailed mechanisms are still unknown. Dried leaves of D. pentagyna were extracted with ethanol and termed as an ethanolic extract of leaves of D. pentagyna (EELDP). Our aim was to elucidate the role of EELDP in in-vitro cell migration and apoptosis in highly metastatic human lung adenocarcinoma A549 cells. We measured cell viability and in-vitro cell migration in three different human cancer cells A549, HeLa and U2OS treated with EELDP (0-0.6 mg/mL). However, A549 cells showed higher sensitivity to EELDP treatment. Hence we studied several key markers of metastasis and apoptosis pathway in A549 cells treated with EELDP. EELDP treatment significantly reduced in-vitro cell migration, wound healing, expression and activity of MMP-2, MMP-9 via reduction of nuclear factor kappa Beta (NF-κβ). EELDP also reduced vimentin, N-cadherin and increased claudin-1. The intrinsic pathway of apoptosis was triggered by EELDP via the NF-κβ pathway through the increase of the Bax to Bcl2 ratio, leading to the fall of mitochondrial membrane potential and subsequently induced release of cytochrome c, activation of caspase-3 followed by nuclear fragmentation in A549 cells. Furthermore, we observed change of a few markers of metastasis and apoptosis in other two cell types HeLa and U2OS treated with EELDP. These data implicate that the effect of EELDP is not cell-specific. Since only 0.1 mg/mL EELDP significantly reduces in-vitro cell migration and increases apoptosis, the active compound(s) present in EELDP is very much potent to control highly metastatic cancer. 相似文献
53.
Protoachlya nainitalensis isolated from mixed oak forest soil (Quercus leucotrichophora & Q. floribunda) is described herein. The species is characterised by elongated, cylindrical, smooth walled zoosporangia; spherical and smooth walled oogonia with androgynous and rarely diclinous branches of antheridia. A simplified key of the known Protoachlya species has also been established. 相似文献
54.
Upadhyay R Shukla A Gaur K 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2002,105(8):1215-1219
Four hybrids (4 F1s) were chosen out of crosses in the urdbean [Vigna mungo (L.) Hepper, 2n = 22] having contrasting morphological characters. Zymograms for isozyme peroxidase were drawn from the patterns obtained from parents and their respective F1 hybrids on the basis of relative similarities to parental bands. The selfed or crossed nature of hybrid pods was determined from the zymograms and their analysis. The number of bands and their intensities gave an idea about the extent of crossing in F1 populations. Genetic identity (I) values were indicative of their selfed nature. Dendrograms were constructed on the basis of genetic identity values to display the relative similarities between the populations. Analysis was based on individual pods to confirm their hybrid or selfed nature. Possible use of this technique for identification of F1 pods and elimination of selfed pods might be implemented to shorten the breeding operations during crossing. 相似文献
55.
Strains ofM. ciceri, symbionts of chickpea (Cicer arietinum) were incubated with the flavonoids naringenin, daidzein and quercetin which have earlier been reported as inducers and inhibitors
ofnodABC-lacZ fusion ofM. ciceri. Preincubation ofM. ciceri with naringenin and daidzein (100 nmol/L) for 1 d improved the competitive ability of the inoculated strain while preincubation
with quercetin decreased the nodule occupancy of inoculated strain under sterile conditions. Under nonsterile conditions induced
strains of Rcd 301 and HT-6 formed by 23 and 18% more nodules, respectively, than untreated control. Quercetin-treated strains
showed by 13–20% fewer nodules than untreated controls. Therefore, it is possible to regulate the competitive ability of inoculated
strains by flavonoid treatment. 相似文献
56.
Differential action of iodine on mitochondria from human tumoral- and extra-tumoral tissue in inducing the release of apoptogenic proteins 总被引:2,自引:0,他引:2
Iodide is actively concentrated in the thyroid gland for thyroid hormone biosynthesis. Excess iodine has been observed to induce apoptosis in thyrocytes and mammary cells. The mechanism of iodine induced apoptosis is poorly understood. Among various cell organelles, mitochondria is known to provide conducive environment for the organification of iodine, i.e. iodination of different proteins. Mitochondria also play a central role in execution of apoptosis. To study the role of mitochondria in iodine induced apoptosis, we investigated the direct interaction of iodine and human breast mitochondria vis-a-vis its role in the initiation of apoptosis in vitro. We observed that mitochondria isolated from the tumor (TT) and extra-tumoral tissue (ET) of human breast display significant uptake of iodine. Mitochondrial proteins were observed to be predominantly iodinated in ET but not in TT mitochondria. Treatment with iodine showed an increase in mitochondrial permeability transition of TT and decrease in ET. Iodine induced released factor(s) other than cytochrome c from tumor mitochondria initiate(s) apoptosis in vitro, while those from ET mitochondria were non-apoptogenic in nature. To our knowledge, this is first report demonstrating that iodine acts differentially on mitochondria of tumor and extratumoral origin to release apoptogenic proteins from TT and has a protective effect on ET. 相似文献
57.
Asbestos causes asbestosis and various malignancies by mechanisms that are not clearly defined. Here, we review the accumulating evidence showing that asbestos is directly genotoxic by inducing DNA strand breaks (DNA-SB) and apoptosis in relevant lung target cells. Although the exact mechanisms by which asbestos causes DNA damage and apoptosis are not firmly established, some of the implicated mechanisms include the generation of iron-derived reactive oxygen species (ROS) as well as reactive nitrogen species (RNS), alteration in the mitochondrial function, and activation of the death receptor pathway. We focus on the accumulating evidence implicating ROS. DNA repair mechanisms have a key role in limiting the extent of DNA damage. Recent studies show that asbestos activates DNA repair enzymes such as apurinic/apyrimidinic endonuclease (APE) and poly (ADP-ribose) polymerase (PARP). Asbestos-induced neoplastic transformation may result in the setting where DNA damage overwhelms DNA repair in the face of a persistent proliferative signal. Strategies aimed at limiting asbestos-induced oxidative stress may reduce DNA damage and, as such, prevent malignant transformation. 相似文献
58.
Rifampicin (Rif) is a first line drug used for tuberculosis treatment. However, the emergence of drug resistant strains has necessitated synthesis and testing of newer analogs of Rif. Mycobacterium smegmatis is often used as a surrogate for M. tuberculosis. However, the presence of an ADP ribosyltransferase (Arr) in M. smegmatis inactivates Rif, rendering it impractical for screening of Rif analogs or other compounds when used in conjunction with them (Rif/Rif analogs). Rifampicin is also used in studying the role of various DNA repair enzymes by analyzing mutations in RpoB (a subunit of RNA polymerase) causing Rif resistance. These analyses use high concentrations of Rif when M. smegmatis is used as model. Here, we have generated M. smegmatis strains by deleting arr (Δarr). The M. smegmatis Δarr strains show minimum inhibitory concentration (MIC) for Rif which is similar to that for M. tuberculosis. The MICs for isoniazid, pyrazinamide, ethambutol, ciprofloxacin and streptomycin were essentially unaltered for M. smegmatis Δarr. The growth profiles and mutation spectrum of Δarr and, Δarr combined with ΔudgB (udgB encodes a DNA repair enzyme that excises uracil) strains were similar to their counterparts wild-type for arr. However, the mutation spectrum of ΔfpgΔarr strain differed somewhat from that of the Δfpg strain (fpg encodes a DNA repair enzyme that excises 8-oxo-G). Our studies suggest M. smegmatis Δarr strain as an ideal model system in drug testing and mutation spectrum determination in DNA repair studies. 相似文献
59.
Transfecting pDNA to E. coli DH5α using bovine serum albumin nanoparticles as a delivery vehicle 下载免费PDF全文
Jitendra Wagh Kuldeep J. Patel Parth Soni Krutika Desai Pratik Upadhyay Hemant P. Soni 《Luminescence》2015,30(5):583-591
We describe the formulation of bovine serum albumin nanoparticles (BSA‐NPs) by the coacervation method using surfactants. Plasmids (pUC18, pUC18egfp and pBBR1MCS‐2) isolated from E. coli were incorporated into the BSA matrix by incubating in albumin solution prior to formulation of NPs. Plasmid incorporation was calculated by % yield, entrapment efficiency, DNA loading capacity and release of entrapped DNA by comparing with blank NPs. BSA‐DNA binding studies were carried out by using fluorescence spectroscopy and Fourier Transform Infra Red Spectroscopy (FT‐IR). The surface charge distribution of the NPs loaded with plasmid was calculated using zeta potential. The photoluminescence of BSA‐NPs was quenched when loaded with pDNA, confirming the interaction of DNA with BSA. Altogether, these results provide evidences for the excellent DNA carrying efficiency of BSA‐NPs without loss of plasmid's integrity. The NPs were used to transfect E. coli DH5α strain lacking ampicillin resistance. They, however, showed ampicillin resistance subsequent to transfection with plasmid encoding ampicillin resistance gene. Effect of transfection was confirmed by confocal microscopy and by the isolation of the plasmid by agarose gel electrophoresis from the transfected bacterial culture. This study clearly demonstrates the efficacy of BSA‐NPs as delivery vehicle for pDNA transfection. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
60.
Poornima L. N. Kotha Priyanka Sharma Abimbola O. Kolawole Ran Yan Mahmoud S. Alghamri Trisha L. Brockman Julian Gomez-Cambronero Katherine J. D. A. Excoffon 《PLoS pathogens》2015,11(3)
Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR), a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAREx8 may be to facilitate host innate immunity. We show that IL-8, a proinflammatory cytokine and a neutrophil chemoattractant, stimulates the protein expression and apical localization of CAREx8 via activation of AKT/S6K and inhibition of GSK3β. Apical CAREx8 tethers infiltrating neutrophils at the apical surface of a polarized epithelium. Moreover, neutrophils present on the apical-epithelial surface enhance adenovirus entry into the epithelium. These findings suggest that adenovirus evolved to co-opt an innate immune response pathway that stimulates the expression of its primary receptor, apical CAREx8, to allow the initial infection the intact epithelium. In addition, CAREx8 is a new target for the development of novel therapeutics for both respiratory inflammatory disease and adenoviral infection. 相似文献