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121.
Subash Chandra Mohapatra Hemandra Kumar Tiwari Manisha Singla Brijesh Rathi Arun Sharma Kuldeep Mahiya Mukesh Kumar Saket Sinha Shyam Singh Chauhan 《Journal of biological inorganic chemistry》2010,15(3):373-385
A new class of copper(II) nanohybrid solids, LCu(CH3COO)2 and LCuCl2, have been synthesized and characterized by transmission electron microscopy, dynamic light scattering, and IR spectroscopy,
and have been found to be capped by a bis(benzimidazole) diamide ligand (L). The particle sizes of these nanohybrid solids
were found to be in the ranges 5–10 and 60–70 nm, respectively. These nanohybrid solids were evaluated for their in vitro
antimalarial activity against a chloroquine-sensitive isolate of Plasmodium falciparum (MRC 2). The interactions between these nanohybrid solids and plasmepsin II (an aspartic protease and a plausible novel target
for antimalarial drug development), which is believed to be essential for hemoglobin degradation by the parasite, have been
assayed by UV–vis spectroscopy and inhibition kinetics using Lineweaver–Burk plots. Our results suggest that these two compounds
have antimalarial activities, and the IC50 values (0.025–0.032 μg/ml) are similar to the IC50 value of the standard drug chloroquine used in the bioassay. Lineweaver–Burk plots for inhibition of plasmepsin II by LCu(CH3COO)2 and LCuCl2 show that the inhibition is competitive with respect to the substrate. The inhibition constants of LCu(CH3COO)2 and LCuCl2 were found to be 10 and 13 μM, respectively. The IC50 values for inhibition of plasmepsin II by LCu(CH3COO)2 and LCuCl2 were found to be 14 and 17 μM, respectively. Copper(II) metal capped by a benzimidazole group, which resembles the histidine
group of copper proteins (galactose oxidase, β-hydroxylase), could provide a suitable anchoring site on the nanosurface and
thus could be useful for inhibition of target enzymes via binding to the S1/S3 pocket of the enzyme hydrophobically. Both
copper(II) nanohybrid solids were found to be nontoxic against human hepatocellular carcinoma cells and were highly selective
for plasmepsin II versus human cathepsin D. The pivotal mechanism of antimalarial activity of these compounds via plasmepsin
II inhibition in the P. falciparum malaria parasite is demonstrated. 相似文献
122.
Pranab Kishor Mohapatra Lichita Patro Mukesh Kumar Raval Nemmara Krishnan Ramaswamy Udaya Chand Biswal Basanti Biswal 《Physiologia plantarum》2010,138(3):346-355
A link between senescence‐induced decline in photosynthesis and activity of β‐glucosidase is examined in the leaves of Arabidopsis. The enzyme is purified and characterized. The molecular weight of the enzyme is 58 kDa. It shows maximum activity at pH 5.5 and at temperature of 50°C. Photosynthetic measurements and activity of the enzyme are conducted at different developmental stages including senescence of leaves. Senescence causes a significant loss in total chlorophyll, stomatal conductance, rate of evaporation and in the ability of the leaves for carbon dioxide fixation. The process also brings about a decline in oxygen evolution, quantum yield of photosystem II (PS II) and quantum efficiency of PS II photochemistry of thylakoid membrane. The loss in photosynthesis is accompanied by a significant increase in the activity of the cell wall‐bound β‐glucosidase that breaks down polysaccharides to soluble sugars. The loss in photosynthesis as a signal for the enhancement in the activity of the enzyme is confirmed from the observation that incubation of excised mature leaves in continuous dark or in light with a photosynthesis inhibitor 3‐(3,4‐dichlorophenyl)‐1, 1‐dimethylurea (DCMU) that leads to sugar starvation enhances the activity of the enzyme. The work suggests that in the background of photosynthetic decline, the polysaccharides bound to cell wall that remains intact even during late phase of senescence may be the last target of senescing leaves for a possible source of sugar for remobilization and completion of the energy‐dependent senescence program. 相似文献
123.
Biochemical and fluorescence microscopic imaging approach has been adopted to investigate the accumulation of oil bodies at specific stages of seed development in Helianthus annuus L. cv. Morden. Seed filling in sunflower is marked with a rapid accumulation of proteins and lipids upto 30 DAA, after which protein accumulation declines whereas lipids continue to accumulate. Earliest signs of lipid accumulation are evident as early as during globular stage of embryo development. Spatially, a developing seed exhibits enhanced lipid deposition in peripheral cells. Oil body biogenesis is observed as early as 10 DAA, as is evident from the fluorescence microscopic detection of Nile red-positive entities in the protoplasts. To begin with, expression of one of the oleosin (the principal oil body membrane proteins) isoforms (16 kDa), is slower than the other two (17.5 and 20 kDa). Fatty acid composition of oil body lipids is quite similar to that of total seed lipids. An enhanced accumulation of linoleic acid is evident during later stages of seed filling. The proportion of major saturated fatty acids, palmitic (16:0) and stearic (18:0), however, do not alter much during the later phases of seed development. Present findings provide new information on oil body development, lipid accumulation and fatty acid composition, for a better understanding of the phasing of physiological and biochemical events associated with oilseed development. 相似文献
124.
Mukesh Saxena Mayuresh Abhyankar Deepak Bastia 《The Journal of biological chemistry》2010,285(8):5705-5712
Plasmid R6K, which contains 3 replication origins called α, γ, and β, is a favorable system to investigate the molecular mechanism(s) of action at a distance, i.e. replication initiation at a considerable distance from the primary initiator protein binding sites (iterons). The centrally located γ origin contains 7 iterons that bind to the plasmid-encoded initiator protein, π. Ori α, located at a distance of ∼4 kb from γ, contains a single iteron that does not directly bind to π but is believed to access the protein by π-mediated α-γ iteron-iteron interaction that loops out the intervening ∼3.7 kb of DNA. Although the cis-acting components and the trans-acting proteins required for ori γ function have been analyzed in detail, such information was lacking for ori α. Here, we have identified both the sequence elements located at α and those at γ, that together promoted α activity. The data support the conclusion that besides the single iteron, a neighboring DNA primase recognition element called G site is essential for α-directed plasmid maintenance. Sequences preceding the iteron and immediately following the G site, although not absolutely necessary, appear to play a role in efficient plasmid maintenance. In addition, while both dnaA1 and dnaA2 boxes that bind to DnaA protein and are located at γ were essential for α activity, only dnaA2 was required for initiation at γ. Mutations in the AT-rich region of γ also abolished α function. These results are consistent with the interpretation that a protein-DNA complex consisting of π and DnaA forms at γ and activates α at a distance by DNA looping. 相似文献
125.
126.
Claire Gaillard Mukesh Singh Kulbhushan Kumar Rishi Vipnesh Bhardwaj 《Comptes Rendus Palevol》2010,9(5):237-243
The largest collection of Acheulian artefacts in the Siwalik region is from the site of Atbarapur in north-western India. The artefacts occur in reworked sediments of the Pinjore Formation, starting with the onset of the Pleistocene and continuing at places in this region till 0.6 Ma. The technical study shows two similar “chaînes opératoires”: one based on cobbles for making small flakes and the second based on boulders for large flakes. Both are short and simple: cores are not prepared and each of them produced about seven flakes. Handaxes and cleavers, typical Acheulian tools, are made on the large flakes, often struck from the ventral face of larger flakes (Kombewa method) or from split boulders. The technology compares well with the Lower Pleistocene Acheulian of peninsular India, but with slightly more refined bifaces. It also compares with assemblages from Africa and East Asia: Atbarapur stands as a milestone on the diffusion route(s) of the Acheulian. 相似文献
127.
128.
Although apoptosis can be readily assessed in vitro with a variety of techniques, the detection of apoptosis in the in vivo setting poses a much more difficult proposition. Apoptosis in an organism is followed almost inevitably by rapid clearance of dying cells via phagocytosis, thus limiting the ability to analyze apoptosis in vivo using classical techniques. To address this issue, we developed a method to enhance in vivo apoptosis detection using pretreatment with chloroquine, an inhibitor of macrophage activity, in Swiss albino mice. This technique resulted in a significant increase in the accumulation of apoptotic cells induced by 5-fluorouracil, as detected by propidium iodide staining in solid and ascitic forms of Ehrlich ascitic tumors and in bone marrow cells. We further validated our technique using DNA fragmentation and endonuclease assays. Our results demonstrated that chloroquine pretreatment can significantly enhance accumulation of apoptotic cells in organisms, and we envision combining this method with modern imaging techniques to optimize in vivo detection of apoptosis. 相似文献
129.
Ahmed Kamal D. Rajasekhar Reddy M. Kashi Reddy G. Balakishan T. Basha Shaik Mukesh Chourasia G. Narahari Sastry 《Bioorganic & medicinal chemistry》2009,17(4):1557-1572
C2-Fluoro substituted DC-81, and its dimers that comprise of two C2-fluoro substituted DC-81 subunits tethered to their C8-position through simple alkane spacers as well as piperazine moiety side-armed with symmetrical alkyloxy spacers have been designed and synthesized. These fluoro substituted pyrrolo[2,1-c][1,4]benzodiazepines have shown remarkable DNA-binding ability and most of them possess promising anticancer activity, having GI50 values in micromolar to nanomolar concentration range. DNA thermal denaturation studies show that some of these compounds (14a–c and 15) increase the ΔTm values in the range of 28.9–38 °C, and this is further confirmed by the restriction endonuclease studies. This study illustrates the importance of introducing fluoro substitution at the C2-position apart from the incorporation of a piperazine ring in between the alkyloxy linker for enhancement of the DNA-binding ability in comparison to DSB-120 and SJG-136 (ΔTm = 10.2 and 25.7 °C). Moreover, the variations in the DNA-binding ability with respect to fluoro substitution in this class of dimers has been investigated by molecular modeling studies. Some representative C2-fluoro substituted dimers (8a and 14a) have also exhibited significant anticancer activity in the 60 cancer cell line assay of the National Cancer Institute (NCI). 相似文献
130.
Transforming growth factor-beta1 inhibition of vascular smooth muscle cell activation is mediated via Smad3 总被引:4,自引:0,他引:4
Feinberg MW Watanabe M Lebedeva MA Depina AS Hanai J Mammoto T Frederick JP Wang XF Sukhatme VP Jain MK 《The Journal of biological chemistry》2004,279(16):16388-16393
Activation of vascular smooth muscle cells (VSMCs) by proinflammatory cytokines is a key feature of atherosclerotic lesion formation. Transforming growth factor (TGF)-beta1 is a pleiotropic growth factor that can modulate the inflammatory response in diverse cell types including VSMCs. However, the mechanisms by which TGF-beta1 is able to mediate these effects remains incompletely understood. We demonstrate here that the ability of TGF-beta1 to inhibit markers of VSMC activation, inducible nitric-oxide synthase (iNOS) and interleukin (IL)-6, is mediated through its downstream effector Smad3. In reporter gene transfection studies, we found that among a panel of Smads, Smad3 could inhibit iNOS induction in an analogous manner as exogenous TGF-beta1. Adenoviral overexpression of Smad3 potently repressed inducible expression of endogenous iNOS and IL-6. Conversely, TGF-beta1 inhibition of cytokine-mediated induction of iNOS and IL-6 expression was completely blocked in Smad3-deficient VSMCs. Previous studies demonstrate that CCAAT/enhancer-binding protein (C/EBP) and NF-kappaB sites are critical for cytokine induction of both the iNOS and IL-6 promoters. We demonstrate that the inhibitory effect of Smad3 occurs via a novel antagonistic effect of Smad3 on C/EBP DNA-protein binding and activity. Smad3 mediates this effect in part by inhibiting C/EBP-beta and C/EBP-delta through distinct mechanisms. Furthermore, we find that Smad3 prevents the cooperative induction of the iNOS promoter by C/EBP and NF-kappaB. These data demonstrate that Smad3 plays an essential role in mediating TGF-beta1 anti-inflammatory response in VSMCs. 相似文献