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31.
J Klein J Gonzalez J Duchene L Esposito JP Pradère E Neau C Delage D Calise A Ahluwalia P Carayon JB Pesquero M Bader JP Schanstra JL Bascands 《FASEB journal》2009,23(1):134-142
Renal fibrosis is the common histological feature of advanced glomerular and tubulointerstitial disease leading to end-stage renal disease (ESRD). However, specific antifibrotic therapies to slow down the evolution to ESRD are still absent. Because persistent inflammation is a key event in the development of fibrosis, we hypothesized that the proinflammatory kinin B1 receptor (B1R) could be such a new target. Here we show that, in the unilateral ureteral obstruction model of renal fibrosis, the B1R is overexpressed and that delayed treatment with an orally active nonpeptide B1R antagonist blocks macrophage infiltration, leading to a reversal of the level of renal fibrosis. In vivo bone marrow transplantation studies as well as in vitro studies on renal cells show that part of this antifibrotic mechanism of B1R blockade involves a direct effect on resident renal cells by inhibiting chemokine CCL2 and CCL7 expression. These findings suggest that blocking the B1R is a promising antifibrotic therapy. 相似文献
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Procerain B, a novel cysteine protease (endopeptidase) isolated from Calotropis procera belongs to Asclepiadaceae family. Purification of the enzyme, biochemical characterization and potential applications are already published by our group. Here, we report cDNA cloning, complete amino acid sequencing and molecular modeling of procerain B. The derived amino acid sequence showed high sequence homology with other papain like plant cysteine proteases of peptidase C1A superfamily. The three dimensional structure of active procerain B was modeled by homology modeling using X-ray crystal structure of actinidin (PDB ID: 3P5U), a cysteine protease from the fruits of Actinidia arguta. The structural aspect of the enzyme is also discussed. 相似文献
35.
Arun P. Chandrasekharappa Sangamesh E. Badiger Pramod K. Dubey Sunil K. Panigrahi Sekhar Reddy V.V.V. Manukonda 《Bioorganic & medicinal chemistry letters》2013,23(9):2579-2584
A series of benzoxazole compounds containing oxamic acid were synthesized and screened for the PTP1B inhibition. Compound 31d showed best biochemical potency (Ki) of 6.7 μM. Structure–activity relationship were explained with the help of molecular modeling approach. 相似文献
36.
Sudipta Hazra Subhalakshmi Ghosh Madhushree Das Sarma Smriti Sharma Mousumi Das Prakash Saudagar Vijay Kumar Prajapati Vikash Kumar Dubey Shyam Sundar Banasri Hazra 《Experimental parasitology》2013
World health organization has called for academic research and development of new chemotherapeutic strategies to overcome the emerging resistance and side effects exhibited by the drugs currently used against leishmaniasis. Diospyrin, a bis-naphthoquinone isolated from Diospyros montana Roxb., and its semi-synthetic derivatives, were reported for inhibitory activity against protozoan parasites including Leishmania. Presently, we have investigated the antileishmanial effect of a di-epoxide derivative of diospyrin (D17), both in vitro and in vivo. Further, the safety profile of D17 was established by testing its toxicity against normal macrophage cells (IC50 ∼ 20.7 μM), and also against normal BALB/c mice in vivo. The compound showed enhanced activity (IC50 ∼ 7.2 μM) as compared to diospyrin (IC50 ∼ 12.6 μM) against Leishmania donovani promastigotes. Again, D17 was tested on L. donovani BHU1216 isolated from a sodium stibogluconate-unresponsive patient, and exhibited selective inhibition of the intracellular amastigotes (IC50 ∼ 0.18 μM). Also, treatment of infected BALB/c mice with D17 at 2 mg/kg/day reduced the hepatic parasite load by about 38%. Subsequently, computational docking studies were undertaken on selected enzymes of trypanothione metabolism, viz. trypanothione reductase (TryR) and ornithine decarboxylase (ODC), followed by the enzyme kinetics, where D17 demonstrated non-competitive inhibition of the L. donovani ODC, but could not inhibit TryR. 相似文献
37.
Manju Shri Arti Rai Pankaj Kumar Verma Prashant Misra Sonali Dubey Smita Kumar Sikha Verma Neelam Gautam Rudra Deo Tripathi Prabodh Kumar Trivedi Debasis Chakrabarty 《Protoplasma》2013,250(2):631-636
Agrobacterium-mediated transformation of indica rice varieties has been quite difficult as these are recalcitrant to in vitro responses. In the present study, we established a high-efficiency Agrobacterium tumefaciens-mediated transformation system of rice (Oryza sativa L. ssp. indica) cv. IR-64, Lalat, and IET-4786. Agrobacterium strain EHA-101 harboring binary vector pIG121-Hm, containing a gene encoding for β-glucuronidase (GUS) and hygromycin resistance, was used in the transformation experiments. Manipulation of different concentrations of acetosyringone, days of co-culture period, bacterial suspension of different optical densities (ODs), and the concentrations of l-cysteine in liquid followed by solid co-culture medium was done for establishing the protocol. Among the different co-culture periods, 5 days of co-culture with bacterial cells (OD600 nm?=?0.5–0.8) promoted the highest frequency of transformation (83.04 %) in medium containing l-cysteine (400 mg l?1). Putative transformed plants were analyzed for the presence of a transgene through genomic PCR and GUS histochemical analyses. Our results also suggest that different cultural conditions and the addition of l-cysteine in the co-culture medium improve the Agrobacterium-mediated transformation frequencies from an average of 12.82 % to 33.33 % in different indica rice cultivars. 相似文献
38.
Ashwini Godbole Ashvini Kumar Dubey Palakolanu S. Reddy M. Udayakumar Mathew K. Mathew 《Protoplasma》2013,250(4):875-884
The voltage-dependent anion channel (VDAC) and mitochondrially located hexokinase have been implicated both in pathways leading to cell death on the one hand, and immortalization in tumor formation on the other. While both proteins have also been implicated in death processes in plants, their interaction has not been explored. We have examined cell death following heterologous expression of a rice VDAC in the tobacco cell line BY2 and in leaves of tobacco plants and show that it is ameliorated by co-expression of hexokinase. Hexokinase also abrogates death induced by H2O2. We conclude that the ratio of expression of the two proteins and their interaction play a major role in modulating death pathways in plants. 相似文献
39.
An indigenously isolated fungal strain Aspergillus flavus MTCC 10938 was subjected to pectin lyase (PNL) production under submerged fermentation conditions. The enzyme was purified to homogeneity from the culture filtrate of the fungus involving concentration by ultrafiltration, anion exchange chromatography on DEAE cellulose and gel filtration chromatography on Sephadex G-100. The purified PNL gave a single protein band in SDS-PAGE analysis with a relative molecular mass corresponding to 50 kDa. Using citrus pectin as the substrate the K m and k cat values of the enzyme were obtained as 1.7 mg/ml and 66 s?1, respectively. The optimum pH of the purified PNL from A. flavus MTCC 10938 was 8.0 and up to 90% of its activity retained in the pH range from 3.0 to 11.0 after 24 h incubation. The optimum temperature of the purified enzyme was revealed at 55°C and it was completely stable up to 40°C when exposed for 30 min. The purified A. flavus MTCC 10938 PNL showed efficient retting of Crotalaria juncea fibres. 相似文献
40.
Seedlings of two Indica rice (Oryza sativa L.) cvs. HUR-105 and Vandana, differing in Al-tolerance were used to identify the key mechanisms involved in their differential behaviour towards Al toxicity. Cv. HUR-105 appeared to be Al sensitive by showing significant reduction (p ≤ 0.01) in root/shoot length, fresh weight, dry weight and water content in presence of 421 μM Al3+ in growth medium whereas cv. Vandana appeared to be fairly Al3+ tolerant. A conspicuous and significant reduction in dry weight of root and shoot was observed in Al sensitive cv. HUR-105 with 178 μM Al3+ treatment for 3 days. Al was readily taken up by the roots and transported to shoots in both the rice cultivars. Localization of absorbed Al was always greater in roots than in shoots. Our results of the production of reactive oxygen species (ROS) H2O2 and O2 .? and activities of major antioxidant enzymes such as total superoxide dismutase (SOD), Cu/Zn SOD, Mn SOD, Fe SOD, catalase (CAT) and guaiacol peroxidase revealed Al induced higher oxidative stress, greater production of ROS and lesser capacity to scavenge ROS in cv. HUR-105 than Vandana. With Al treatment, higher oxidative stress was noted in shoots than in roots. Greatly enhanced activities of SOD (especially Fe and Mn SOD) and CAT in Al treated seedlings of cv. Vandana suggest the role of these enzymes in Al tolerance. Furthermore, a marked presence of Fe SOD in roots and shoots of the seedlings of Al tolerant cv. Vandana and its significant (p ≤ 0.01) increase in activity due to Al-treatment, appears to be the unique feature of this cultivar and indicates a vital role of Fe SOD in Al-tolerance in rice. 相似文献