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131.
Belo A Cheng K Chahdi A Shant J Xie G Khurana S Raufman JP 《American journal of physiology. Gastrointestinal and liver physiology》2011,300(5):G749-G760
Muscarinic receptors (CHRM) are overexpressed in colon cancer. To explore a role for muscarinic receptor signaling in colon cancer metastasis, we used human H508 and HT29 colon cancer cells that coexpress epidermal growth factor (ERBB) and CHRM3 receptors. In a wound closure model, following 8-h incubation of H508 cells with 100 μM ACh we observed a threefold increase in cell migration indistinguishable from the actions of epidermal growth factor (EGF). Atropine blocked the actions of ACh but not of EGF. In SNU-C4 colon cancer cells that express ERBB but not CHRM, EGF caused a threefold increase in migration; ACh had no effect. ACh-induced cell migration was attenuated by chemical inhibitors of ERBB1 activation, by anti-ERBB1 antibody, and by inhibitors of ERK and phosphatidylinositol 3-kinase (PI3K) signaling. Consistent with matrix metalloproteinase-7 (MMP7)-mediated release of an ERBB1 ligand, heparin binding epidermal growth factor-like growth factor (HBEGF), ACh-induced migration was inhibited by an MMP inhibitor and by anti-MMP7 and -HBEGF antibodies. ACh-induced cell migration was blocked by inhibiting RhoA and ROCK, key proteins that interact with the actin cytoskeleton. ACh-induced RhoA activation was attenuated by agents that inhibit ERBB1, ERK, and PI3K activation. Collectively, these findings indicate that ACh-induced cell migration is mediated by MMP7-mediated release of HBEGF, an ERBB ligand that activates ERBB1 and downstream ERK and PI3K signaling. In a cell invasion model, ACh-induced HT29 cell invasion was blocked by atropine. In concert with previous observations, these findings indicate that muscarinic receptor signaling plays a key role in colon cancer cell proliferation, survival, migration, and invasion. 相似文献
132.
Ashima Khurana Jitendra P. Khurana Shashi B. Babbar 《Journal of Plant Growth Regulation》2011,30(3):378-385
Nitric oxide (NO) plays diverse roles in the growth and development of plants and in their responses to various abiotic and
biotic stresses. It has also been reported to repress flowering in Arabidopsis thaliana. In the present study, NO donors sodium nitroprusside (SNP), S-nitroso-N-acetyl penicillamine (SNAP), and 3-morpholinosydnonimine (SIN-1) induced flowering in Lemna
aequinoctialis 6746 (a short-day strain) and in L.
aequinoctialis LP6 (a photoperiod-insensitive strain) under noninductive conditions. Nitrate and nitrite, two stable metabolites of NO, did
not induce flowering. On the other hand, cyanide donors potassium ferricyanide {K3[Fe(CN)6]} and potassium cyanide (KCN) induced flowering in both strains under noninductive conditions. The flowering induced under
a 8-h daily photoperiod regime in the short-day strain L.
aequinoctialis 6746 was inhibited by NO and cyanide donors. Vegetative multiplication of both strains was adversely affected by NO and cyanide
donors, irrespective of the photoperiod conditions. The observed effects of NO donors on flowering were substantially negated
by NO scavengers c-PTIO [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide] and methylene blue. This confirmed
the role of NO in induction of flowering. The inductive effect of CN− also appeared to be partly mediated through NO as NO scavengers partially negated the effect of CN−. 相似文献
133.
Angiosperms are characterized by the occurrence of double fertilization. However, Podostemaceae is considered an exception
with the presence of only single fertilization (syngamy) though two male gametes are formed conventionally. To determine the
cause for the failure of double fertilization in Dalzellia zeylanica (Gardn.) Wight, we closely tracked the movement of the male gametes from the time of pollen tube initiation to the time of
entry into the megagametophyte to affect fertilization. We report for the first time, the presence of a novel type of three-nucleate/three-celled
mature megagametophyte consisting of two synergids and an egg cell in D. zeylanica. Therefore, of the two male gametes formed in this plant, one fuses with the egg cell resulting in syngamy, whereas the other
male gamete eventually degenerates due to the absence of its partner i.e. single polar nucleus of the central cell that degenerates
prior to the entry of the pollen tube into the synergid. The present work not only highlights the highly reduced nature of
megagametophyte but also the occurrence of single fertilization resulting in sperm selection in D. zeylanica. 相似文献
134.
Khurana A Shao ES Kim RY Vilin YY Huang X Yang R Kurata HT 《The Journal of biological chemistry》2011,286(42):36686-36693
Numerous inwardly rectifying potassium (Kir) channels possess an aromatic residue in the helix bundle crossing region, forming the narrowest pore constriction in crystal structures. However, the role of the Kir channel bundle crossing as a functional gate remains uncertain. We report a unique phenotype of Kir6.2 channels mutated to encode glutamate at this position (F168E). Despite a prediction of four glutamates in close proximity, Kir6.2(F168E) channels are predominantly closed at physiological pH, whereas alkalization causes rapid and reversible channel activation. These findings suggest that F168E glutamates are uncharged at physiological pH but become deprotonated at alkaline pH, forcing channel opening due to mutual repulsion of nearby negatively charged side chains. The potassium channel pore scaffold likely brings these glutamates close together, causing a significant pK(a) shift relative to the free side chain (as seen in the KcsA selectivity filter). Alkalization also shifts the apparent ATP sensitivity of the channel, indicating that forced motion of the bundle crossing is coupled to the ATP-binding site and may resemble conformational changes involved in wild-type Kir6.2 gating. The study demonstrates a novel mechanism for engineering extrinsic control of channel gating by pH and shows that conformational changes in the bundle crossing region are involved in ligand-dependent gating of Kir channels. 相似文献
135.
Khurana S Wu J Verma N Verma S Raghunandan R Manischewitz J King LR Kpamegan E Pincus S Smith G Glenn G Golding H 《Journal of virology》2011,85(21):10945-10954
Transmission of pathogenic avian influenza viruses (AIV) from wild birds to domestic poultry and humans is continuing in multiple countries around the world. In preparation for a potential AIV pandemic, multiple vaccine candidates are under development. In the case of H5N1 AIV, a clear shift in transmission from clade 1 to clade 2 viruses occurred in recent years. The virus-like particle (VLP) represents an economical approach to pandemic vaccine development. In the current study, we evaluated the humoral immune response in humans vaccinated with H5N1 A/Indonesia/05/2005 (clade 2.1) VLP vaccine manufactured in Sf9 insect cells. The VLPs were comprised of the influenza virus hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1) proteins. In an FDA-approved phase I/II human clinical study, two doses of H5N1 VLPs at 15, 45, or 90 μg HA/dose resulted in seroconversion and production of functional antibodies. Moreover, cross-reactivity against other clade 2 subtypes was demonstrated using virus neutralization assays. H5N1 whole-genome fragment phage display libraries (GFPDL) were used to elucidate the antibody epitope repertoire in postvaccination human sera. Diverse epitopes in HA1/HA2 and NA were recognized by postvaccination sera from the two high-dose groups, including large segments spanning the HA1 receptor binding domain. Importantly, the vaccine elicited sera that preferentially bound to an oligomeric form of recombinant HA1 compared with monomeric HA1. The oligomeric/monomeric HA1 binding ratios of the sera correlated with the virus neutralizing titers. Additionally, the two high-dose VLP vaccine groups generated NA-inhibiting antibodies that were associated with binding to a C-terminal epitope close to the sialic acid binding site. These findings represent the first report describing the quality of the antibody responses in humans following AIV VLP immunization and support further development of such vaccines against emerging influenza virus strains. 相似文献
136.
137.
Manaswini Das Harsh Chauhan Anju Chhibbar Qazi Mohd. Rizwanul Haq Paramjit Khurana 《Transgenic research》2011,20(2):231-246
Osmotin and osmotin-like proteins are stress proteins belonging to the plant PR-5 group of proteins induced in several plant
species in response to various types of biotic and abiotic stresses. We report here the overexpression of tobacco osmotin
in transgenic mulberry plants under the control of a constitutive promoter (CaMV 35S) as well as a stress-inducible rd29A promoter. Southern analysis of the transgenic plants revealed the stable integration of the introduced genes in the transformants.
Real-time PCR analysis provided evidence for the expression of osmotin in the transgenic plants under both the constitutive
and stress-inducible promoters. Transgenic plants with the stress-inducible promoter were observed to better tolerate salt
and drought stress than those with the constitutive promoter. Transgenic plants when subjected to simulated salinity and drought
stress conditions showed better cellular membrane stability (CMS) and photosynthetic yield than non-transgenic plants under
conditions of both salinity and drought stress. Proline levels were very high in transgenic plants with the constitutive promoter
relative to those with the stress-inducible promoter. Fungal challenge undertaken with three fungal species known to cause
serious losses to mulberry cultivation, namely, Fusarium pallidoroseum, Colletotrichum gloeosporioides and Colletotrichum dematium, revealed that transgenic plants with osmotin under control of the constitutive promoter had a better resistance than those with osmotin under the control of the stress-inducible promoter. Evaluation in next generation was undertaken by studying bud break in
transgenic and non-transgenic plants under simulated drought (2% polyethylene glycol) and salt stress (200 mM NaCl) conditions.
The axillary buds of the selected transgenic lines had a better bud break percentage under stressed conditions than buds from
non-transgenic mulberry lines. A biotic assay with Bombyx mori indicated that osmotin protein had no undesirable effect on silkworm rearing and feeding. We therefore conclude that 35S
transgenic plants are better suited for both abiotic stress also biotic challenges (fungal), while the rd29A transgenic plants
are more responsive to drought. 相似文献
138.
Costunolide and its derived C-16 germacranolides on oxidation with selenium dioxide-t-butyl hydroperoxide afforded two melampolides, an aldehydolactone and the corresponding hydroxylactone, in each case. Structures were assigned to these melampolides on the basis of spectral data and chemical correlation. The aldehydolactones were significantly more active root promotors than their parent lactones. Costunolide and related germacranolides underwent cyclization on treatment with iodine and pyridinium chlorochromate to afford interesting products. (?)-β-Frullanolide has been synthesized and shown to be biologically more active when compared with its parent trans-lactone. 相似文献
139.
140.