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81.
Nagavedi S. Umapathy Evgeny A. Zemskov Joyce Gonzales Boris A. Gorshkov Supriya Sridhar Trinad Chakraborty Rudolf Lucas Alexander D. Verin 《Journal of cellular physiology》2010,223(1):215-223
Extracellular β‐NAD is known to elevate intracellular levels of calcium ions, inositol 1,4,5‐trisphate and cAMP. Recently, β‐NAD was identified as an agonist for P2Y1 and P2Y11 purinergic receptors. Since β‐NAD can be released extracellularly from endothelial cells (EC), we have proposed its involvement in the regulation of EC permeability. Here we show, for the first time, that endothelial integrity can be enhanced in EC endogenously expressing β‐NAD‐activated purinergic receptors upon β‐NAD stimulation. Our data demonstrate that extracellular β‐NAD increases the transendothelial electrical resistance (TER) of human pulmonary artery EC (HPAEC) monolayers in a concentration‐dependent manner indicating endothelial barrier enhancement. Importantly, β‐NAD significantly attenuated thrombin‐induced EC permeability as well as the barrier‐compromising effects of Gram‐negative and Gram‐positive bacterial toxins representing the barrier‐protective function of β‐NAD. Immunofluorescence microscopy reveals more pronounced staining of cell–cell junctional protein VE‐cadherin at the cellular periphery signifying increased tightness of the cell‐cell contacts after β‐NAD stimulation. Interestingly, inhibitory analysis (pharmacological antagonists and receptor sequence specific siRNAs) indicates the participation of both P2Y1 and P2Y11 receptors in β‐NAD‐induced TER increase. β‐NAD‐treatment attenuates the lipopolysaccharide (LPS)‐induced phosphorylation of myosin light chain (MLC) indicating its involvement in barrier protection. Our studies also show the involvement of cAMP‐dependent protein kinase A and EPAC1 pathways as well as small GTPase Rac1 in β‐NAD‐induced EC barrier enhancement. With these results, we conclude that β‐NAD regulates the pulmonary EC barrier integrity via small GTPase Rac1‐ and MLCP‐ dependent signaling pathways. J. Cell. Physiol. 223: 215–223, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
82.
Vipen Batra Swathi Sridhar Thomas Paul Asir Devasagayam 《Chemico-biological interactions》2010,183(3):425-433
Radiation exposure poses a major risk for workers in the nuclear power plants and other radiation related industry. In this context, we demonstrate that γ-radiation is an efficient DNA demethylating agent and its injurious effect can be minimized by dietary methyl supplements (folate, choline and vitamin B12). To elucidate the possible underlying mechanism(s), male Swiss mice were maintained on normal control diet (NCD) and methyl-supplemented diet (MSD). After 2 weeks of NCD and MSD dietary regimen, we exposed the animals to γ-radiation (2, 4 and 6 Gy) and investigated the profile of downstream metabolites and activity levels of one-carbon (C1) flux generating enzymes. In MSD fed and irradiated animals, hepatic folate levels increased (P < 0.01), while hepatic homocysteine levels decreased (P < 0.01) compared to NCD fed and irradiated animals. Although hepatic folate level increased significantly in MSD fed animals (P < 0.01), it showed a decrease in response to high doses of γ-irradiation. Under these conditions, a marked suppression of S-adenosylmethionine (SAM) levels occurred in NCD fed and irradiated animals, suggesting reduced conversion of homocysteine to SAM. Concomitant with decline in liver SAM Pool, activities of DNA methyltransferase (Dnmt, that methylates DNA) and methionine synthase (MSase, that regenerates methionine from homocysteine) were both decreased in NCD fed and irradiated mice. However, in MSD fed and irradiated mice, they were increased. These results strongly indicated that increased levels of dnmt and MSase may enhance C1 flux towards DNA methylation reactions in MSD fed animals. These results were confirmed and further substantiated by measuring genomic DNA methylation levels, which were maintained at normal levels in MSD fed and irradiated mice compared to NCD fed and irradiated animals (P < 0.01). In conclusion, our results suggest that maintenance of genomic DNA methylation under γ-radiation stress might be a very dynamic, progressive diet dependent process that could involve increased one-carbon flux through various C1 metabolites. 相似文献
83.
84.
Viamajala S Bereded-Samuel Y Apel WA Petersen JN 《Applied microbiology and biotechnology》2006,71(6):953-962
Selenite reduction by a bacterial consortium enriched from an oil refinery waste sludge was studied under denitrifying conditions using acetate as the electron donor. Fed-batch studies with nitrate as the primary electron acceptor showed that accumulation of nitrite led to a decrease in the extent of selenite reduction. Also, when nitrite was added as the primary electron acceptor, rapid selenite reduction was observed only after nitrite was significantly depleted from the medium. These results indicate that selenite reduction was inhibited at high nitrite concentrations. In addition to batch experiments, continuous-flow selenite reduction experiments were performed in packed-bed columns using immobilized enrichment cultures. These experiments were carried out in three phases: in phase I, a continuous nitrate feed with different inlet selenite concentration was applied; in phase II, nitrate was fed in a pulsed fashion; and in phase III, nitrate was fed in a continuous mode but at much lower concentrations than the other two phases. During the phase I experiments, little selenite was removed from the influent. However, when the column was operated in the pulse feed strategy (phase II) or in the continuous mode with low nitrate levels (phase III), significant quantities of selenium were removed from solution and retained in the immobilization matrix in the column. Thus, immobilized denitrifying cultures can be effective in removing selenium from waste streams, but nitrate-limited operating conditions might be required. 相似文献
85.
Patterns of sequence conservation in presynaptic neural genes 总被引:1,自引:1,他引:0
Hadley D Murphy T Valladares O Hannenhalli S Ungar L Kim J Bućan M 《Genome biology》2006,7(11):R105-19
Background
The neuronal synapse is a fundamental functional unit in the central nervous system of animals. Because synaptic function is evolutionarily conserved, we reasoned that functional sequences of genes and related genomic elements known to play important roles in neurotransmitter release would also be conserved. 相似文献86.
Zhang N Wu B Wissner A Powell DW Rabindran SK Kohler C Boschelli F 《Bioorganic & medicinal chemistry letters》2002,12(3):423-425
A series of 4-anilino-3-cyanobenzo[g]quinolines was prepared as potent kinase inhibitors. Compared with their bicyclic 4-anilino-3-cyanoquinoline analogues, the tricyclic 4-anilino-3-cyanobenzo[g]quinolines are less active against EGF-R kinase, equally active against MAPK kinase (MEK), and more active against Src kinase. For Src kinase inhibition, the best activity is obtained when both the 7- and 8-positions are substituted with alkoxy groups. Several of these kinase inhibitors show potent growth inhibitory activity in tumor cells. 相似文献
87.
Jayshree Mishra Satya Sridhar Karanki Narendra Kumar 《The Journal of biological chemistry》2012,287(49):41386-41391
Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase expressed in both hematopoietic and nonhematopoietic cells. Although mutations that abrogate Jak3 functions cause different immunological disorders, its constitutive activation leads to various types of cancer. Previously, we demonstrated that Jak3 interacted with actin-binding protein villin, thereby facilitating cytoskeletal remodeling and wound repair. In this study, we characterize the structural determinants that regulate the interactions between Jak3 and cytoskeletal proteins of the villin/gelsolin family. Functional reconstitution of kinase activity by recombinant full-length (wt) Jak3 using Jak3-wt or villin/gelsolin-wt as substrate showed that Jak3 autophosphorylation was the rate-limiting step during interactions between Jak3 and cytoskeletal proteins. Determination of kinetic parameters showed that phosphorylated (P) Jak3-wt binds to P-villin-wt with a dissociation constant (Kd) of 23 nm and a Hill''s coefficient of 3.7. Pairwise binding between Jak3 mutants and P-villin-wt showed that the FERM domain of Jak3 was sufficient for binding to P-villin-wt with a Kd of 40.0 nm. However, the SH2 domain of Jak3 prevented P-villin-wt from binding to the FERM domain of nonphosphorylated protein. We demonstrate that the intramolecular interaction between the FERM and SH2 domains of nonphosphorylated Jak3 prevented Jak3 from binding to villin and that tyrosine autophosphorylation of Jak3 at the SH2 domain decreased these intramolecular interactions and facilitated binding of the FERM domain to villin. Thus we demonstrate the molecular mechanism of interactions between Jak3 and cytoskeletal proteins where tyrosine phosphorylation of the SH2 domain acted as an intramolecular switch for the interactions between Jak3 and cytoskeletal proteins. 相似文献
88.
89.
Manchukonda NK Sridhar B Naik PK Joshi HC Kantevari S 《Bioorganic & medicinal chemistry letters》2012,22(8):2983-2987
Facile synthesis of natural α-noscapine analogue, 9-amino-α-noscapine, a potent inhibitor of tubulin polymerization for cancer therapy, is achieved via copper(I) iodide mediated in situ aromatic azidation and reduction of 9-bromo-α-noscapine (obtained by bromination of natural α-noscapine) with NaN(3) in DMSO at 130°C in the presence of L-proline as an amino acid promoter. The protocol developed here avoided isolation of 9-azido-α-noscapine and did not cleave the sensitive C-C bond between two heterocyclic phthalide and isoquinoline units. 相似文献
90.
Yadlapalli RK Chourasia OP Vemuri K Sritharan M Perali RS 《Bioorganic & medicinal chemistry letters》2012,22(8):2708-2711
A series of dihydropyrimidine derivatives were synthesized by utilizing Biginelli reaction and evaluated for their in vitro anticancer activity against MCF-7 human breast cancer (HBC) cell line using sulforhodamine B (SRB) assay and antitubercular activity against Mycobacterium tuberculosis (MTB) H(37)Rv using Microplate Alamar Blue Assay (MABA). Compounds 13p, 13t were exhibited 70.6% and 63.7% of HBC cell growth inhibition at 10 μM concentration. Interestingly compound 13p was also found to be the most potent in the series against MTB H(37)Rv with MIC value of 0.125 μg/mL. 相似文献