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William B Campbell - One of the best experts on this subject based on the ideXlab platform.
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20 iodo 14 15 epoxyeicosa 8 z enoyl 3 azidophenylsulfonamide photoaffinity labeling of a 14 15 epoxyeicosatrienoic acid receptor
Biochemistry, 2011Co-Authors: Yuenmu Chen, John R Falck, Vijaya L Manthati, Jawahar Lal Jat, William B CampbellAbstract:Endothelium-derived epoxyeicosatrienoic acids (EETs) relax vascular smooth muscle by activating potassium channels and causing membrane hyperpolarization. Recent evidence suggests that EETs act via a membrane binding site or receptor. To further characterize this binding site or receptor, we synthesized 20-iodo-14,15-epoxyeicosa-8(Z)-enoyl-3-azidophenylsulfonamide (20-I-14,15-EE8ZE-APSA), an EET analogue with a photoactive azido group. 20-I-14,15-EE8ZE-APSA and 14,15-EET displaced 20-(125)I-14,15-epoxyeicosa-5(Z)-enoic acid binding to U937 Cell membranes with K(i) values of 3.60 and 2.73 nM, respectively. The EET analogue relaxed preconstricted bovine coronary arteries with an ED(50) comparable to that of 14,15-EET. Using electrophoresis, 20-(125)I-14,15-EE8ZE-APSA labeled a single 47 kDa band in U937 Cell membranes, smooth muscle and endothelial Cells, and bovine coronary arteries. In U937 Cell membranes, the 47 kDa radiolabeling was inhibited in a concentration-dependent manner by 8,9-EET, 11,12-EET, and 14,15-EET (IC(50) values of 444, 11.7, and 8.28 nM, respectively). The structurally unrelated EET ligands miconazole, MS-PPOH, and ketoconazole also inhibited the 47 kDa labeling. In contrast, radiolabeling was not inhibited by 8,9-dihydroxyeicosatrienoic acid, 5-oxoeicosatetraenoic acid, a biologically inactive thiirane analogue of 14,15-EET, the opioid antagonist naloxone, the thromboxane mimetic U46619, or the cannabinoid antagonist AM251. Radiolabeling was not detected in membranes from HEK293T Cells expressing 79 orphan receptors. These studies indicate that vascular smooth muscle, endothelial Cells, and U937 Cell membranes contain a high-affinity EET binding protein that may represent an EET receptor. This EET photoaffinity labeling method with a high signal-to-noise ratio may lead to new insights into the expression and regulation of the EET receptor.
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characterization of 14 15 epoxyeicosatrienoyl sulfonamides as 14 15 epoxyeicosatrienoic acid agonists use for studies of metabolism and ligand binding
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: Wenqi Yang, John R Falck, Blythe B Holmes, Raj V Gopal, R Krishna V Kishore, Bhavani Sangras, William B CampbellAbstract:Epoxyeicosatrienoic acids (EETs) are cytochrome P450 epoxygenase metabolites of arachidonic acid. EETs mediate numerous biological functions. In coronary arteries, they regulate vascular tone by the activation of smooth muscle large-conductance, calcium-activated potassium (BKCa) channels to cause hyperpolarization and relaxation. We developed a series of 14,15-EET agonists, 14,15-EET-phenyliodosulfonamide (14,15-EET-PISA), 14,15-EET-biotinsulfonamide (14,15-EET-BSA), and 14,15-EET-benzoyldihydrocinnamide-sulfonamide (14,15-EET-BZDC-SA) as tools to characterize 14,15-EET metabolism and binding. Agonist activities of these analogs were characterized in precontraced bovine coronary arterial rings. All three analogs induced concentration-dependent relaxation and were equipotent with 14,15-EET. Relaxations to these analogs were inhibited by the BKCa channel blocker iberiotoxin (100 nM), the 14,15-EET antagonist 14,15-epoxyeicosa-5( Z )-enoylmethylsulfonamide (10 μM), and abolished by 20 mM extraCellular K+. 14,15-EET-PISA is metabolized to 14,15-dihydroxyeicosatrienoyl-PISA by soluble epoxide hydrolase in bovine coronary arteries and U937 Cells but not U937 Cell membrane fractions. 14,15-EET-P125ISA binding to human U937 Cell membranes was time-dependent, concentration-dependent, and saturable. The specific binding reached equilibrium by 15 min at 4°C and remained unchanged up to 30 min. The estimated K d and B max were 148.3 ± 36.4 nM and 3.3 ± 0.5 pmol/mg protein, respectively. These data suggest that 14,15-EET-PISA, 14,15-EET-BSA, and 14,15-EET-BZDC-SA are full 14,15-EET agonists. 14,15-EET-P125ISA is a new radiolabeled tool to study EET metabolism and binding. Our results also provide preliminary evidence that EETs exert their biological effect through a membrane binding site/receptor.
Chun Che Shih - One of the best experts on this subject based on the ideXlab platform.
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Nickel ions from a corroded cardiovascular stent induce monocytic Cell apoptosis: Proposed impact on vascular remodeling and mechanism
Elsevier, 2015Co-Authors: Chun Ming Shih, Li Rung Liao, Nai-wen Tsao, Hwai-shi Wang, Wei Yuan Chen, Chun Yao Huang, Chiao-po Hsu, Shing-jong Lin, Chun Che ShihAbstract:Monocytes play important roles in inflammatory responses and vascular remodeling after vascular stenting. This research focused on impacts of nickel (Ni) ions released from a corroded cardiovascular stent on cytotoxicity and monocyte activation. Methods: A human promonocytic (macrophage-like) Cell line (U937) was exposed to graduated concentrations of Ni2+ in vitro. Cells were observed and harvested at indicated times to determine the effects using histological and biochemical methods. Results: Ni caused U937 Cell death in dose- and time-dependent manners. In vitro, high concentrations of Ni2+ (>240 μM) significantly induced Cell apoptosis and increased terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL)-positive Cells according to flow cytometric surveillance and triggered apoptotic Cell death. Although no significant changes in Bcl-2 or Bax expressions were detected after 24 hours of Ni2+ treatment, increasing cleavage of caspase-3 and -8 was present. Results showed that cleavage of caspase-8 was inhibited by the presence of the inhibitor, Z-IETD-FMK, and this suggested the presence of Ni2+-induced U937 Cell death through a death receptor-mediated pathway. Simultaneously, when treated with a high concentration of Ni2+ ions, expressions of the vascular remodeling factors, matrix metalloproteinases (MMP)-9 and -2, were activated in dose- and time-dependent manners. Secretion of the proliferative factor, monocyte chemoattractant protein (MCP)-1, significantly increased during the first 6 hours of incubation with 480 μM Ni2+-treated medium. Conclusion: Our results demonstrated that a high concentration of Ni ions causes apoptotic Cell death of circulating monocytes. They may also play different roles in vascular remodeling during the corrosion process following implantation of Ni alloy-containing devices
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Nickel ions from a corroded cardiovascular stent induce monocytic Cell apoptosis: Proposed impact on vascular remodeling and mechanism.
Journal of the Formosan Medical Association, 2014Co-Authors: Chun Ming Shih, Li Rung Liao, Nai-wen Tsao, Hwai-shi Wang, Wei Yuan Chen, Chun Yao Huang, Yea Yang Su, Chun Che ShihAbstract:Background/Purpose Monocytes play important roles in inflammatory responses and vascular remodeling after vascular stenting. This research focused on impacts of nickel (Ni) ions released from a corroded cardiovascular stent on cytotoxicity and monocyte activation. Methods A human promonocytic (macrophage-like) Cell line (U937) was exposed to graduated concentrations of Ni2+ in vitro. Cells were observed and harvested at indicated times to determine the effects using histological and biochemical methods. Results Ni caused U937 Cell death in dose- and time-dependent manners. In vitro, high concentrations of Ni2+ (>240 μM) significantly induced Cell apoptosis and increased terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL)-positive Cells according to flow cytometric surveillance and triggered apoptotic Cell death. Although no significant changes in Bcl-2 or Bax expressions were detected after 24 hours of Ni2+ treatment, increasing cleavage of caspase-3 and -8 was present. Results showed that cleavage of caspase-8 was inhibited by the presence of the inhibitor, Z-IETD-FMK, and this suggested the presence of Ni2+-induced U937 Cell death through a death receptor-mediated pathway. Simultaneously, when treated with a high concentration of Ni2+ ions, expressions of the vascular remodeling factors, matrix metalloproteinases (MMP)-9 and -2, were activated in dose- and time-dependent manners. Secretion of the proliferative factor, monocyte chemoattractant protein (MCP)-1, significantly increased during the first 6 hours of incubation with 480 μM Ni2+-treated medium. Conclusion Our results demonstrated that a high concentration of Ni ions causes apoptotic Cell death of circulating monocytes. They may also play different roles in vascular remodeling during the corrosion process following implantation of Ni alloy-containing devices.
Steven Grant - One of the best experts on this subject based on the ideXlab platform.
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divergent effects of bryostatin 1 and phorbol myristate acetate on Cell cycle arrest and maturation in human myelomonocytic leukemia Cells U937
Differentiation, 1998Co-Authors: Julie A Vrana, Aida M Saunders, Srikumar Chellappan, Steven GrantAbstract:Bryostatin 1 and the phorbol ester, phorbol myristate acetate (PMA), both bind to and activate protein kinase C (PKC) but exhibit divergent biological actions. Bryostatin 1 exerts variable effects on leukemic Cell differentiation, and has been reported by some investigators to inhibit the proliferation of the monocytic leukemic Cell line U937. In this study, we have compared the efficacy of bryostatin 1 and PMA with respect to U937 Cell maturation, with a major emphasis on differential actions on the Cell cycle arrest machinery. At equimolar concentrations (10 nM), PMA, in contrast to bryostatin 1, induced Cellular differentiation of U937 Cells, reflected by growth inhibition, increased plastic adhesion, and expression of the monocytic differentiation marker, CD11b. Consistent with these results, bryostatin 1 was less effective in inducing G0/G1 arrest and inhibiting cyclin-dependent kinase 2 (CDK2) activity. Bryostatin 1, unlike PMA, failed to induce expression of the cyclin-dependent kinase inhibitor (CDKI), p21CIP1/WAF1, and blocked the ability of PMA to induce this protein. Bryostatin 1 exposure resulted in increased expression of the CDKI p27KIP1 in these Cells, although the kinetics differed from PMA. In addition, bryostatin 1 was less effective than PMA in dephosphorylating pRb, modifying E2F complexes, and downregulating c-Myc. Co-administration of bryostatin 1 with PMA antagonized the latter's differentiation-inducing capacity and anti-proliferative effects, actions that were accompanied by a reduction in PMA-mediated p21CIP1/WAF1 induction, CDK2 inhibition, pRb dephosphorylation, and c-Myc downregulation. Antagonistic effects of bryostatin 1 on PMA-related Cell cycle events were mimicked by the specific PKC inhibitor GF109203X. Together, these studies indicate that bryostatin 1 is a considerably weaker stimulus than PMA for U937 Cell differentiation, and raise the possibility that this deficiency arises from its failure to induce p21CIP1/WAF1 and trigger Cell cycle arrest.
Carlos Davio - One of the best experts on this subject based on the ideXlab platform.
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Rapid desensitization and slow recovery of the cyclic AMP response mediated by histamine H2 receptors in the U937 Cell line
Biochemical Pharmacology, 2000Co-Authors: Bibiana Lemos Legnazzi, Federico Monczor, Alberto Baldi, Carina Claudia Shayo, María Eugenia Martín, Natalia Brenda Fernández, Andres L. Brodsky, Carlos DavioAbstract:Abstract The present study focused on the desensitization process of the H 2 receptor in U937 Cells and the recovery of the cyclic AMP (cAMP) response. Treatment of U937 leukemic Cells with the H 2 histamine receptor agonists (±)-N 1 -[3-(3,4-difluorophenyl)-3-(pyridin-2-yl)propyl]-N 2 -[3-(1H-imidazol-4-yl)propyl]guanidine (BU-E-75) and amthamine produced a rapid desensitization characterized by decreased cAMP production (T 1/2 = 20 min). Pretreatment with 10 μM BU-E-75 did not induce modifications in the responses to prostaglandin E 2 , isoproterenol, or forskolin. H 2 receptor desensitization was not affected by protein kinase A and C inhibitors, but was reduced drastically by Zn 2+ and heparin, known to act as inhibitors of G protein-coupled receptor kinases. Recovery studies of the cAMP response showed that cAMP levels reached 50% of the initial values within 5 hr. Furthermore, desensitization produced an important decrease in the basal level of this cyclic nucleotide. The minimal value was observed 12 hr later, and corresponded to approximately 1.3% of the initial basal level (7.5 vs 0.1 pmol/10 6 Cells). This result could be explained by an increase in phosphodiesterase activity following 10 μM BU-E-75 treatment. When Cells were exposed for 2 hr to an H 2 agonist, binding assays showed no modification in the number of H 2 receptors; internalization began just after 8 hr. Although the initial desensitization seems to involve G protein-coupled receptor kinases, results indicate that additional mechanisms of regulation were triggered by the H 2 agonists.
Xuhua Nong - One of the best experts on this subject based on the ideXlab platform.
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new furanone derivatives and alkaloids from the co culture of marine derived fungi aspergillus sclerotiorum and penicillium citrinum
Chemistry & Biodiversity, 2017Co-Authors: Jie Bao, Jie Wang, Xiaoyong Zhang, Xuhua NongAbstract:Six new compounds including two furanone derivatives sclerotiorumins A-B (1-2), one novel oxadiazin derivative sclerotiorumin C (3), one pyrrole derivative 1-(4-benzyl-1H-pyrrol-3-yl)ethanone (4), and two complexes of neoaspergillic acid aluminiumneohydroxyaspergillin (5) and ferrineohydroxyaspergillin (6) were isolated from the co-culture of marine-derived fungi Aspergillus sclerotiorum and Penicillium citrinum. Compound 3 was the first natural 1,2,4-oxadiazin-6-one. Compound 5 showed significant and selective cytotoxicity against human histiocytic lymphoma U937 Cell line (IC50 = 4.2 μM) and strong toxicity towards brine shrimp (LC50 = 6.1 μM), and oppositely increased the growth and biofilm formation of Staphylococcus aureus. This article is protected by copyright. All rights reserved.
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cytotoxic polyketides from the deep sea derived fungus engyodontium album dffscs021
Marine Drugs, 2014Co-Authors: Jie Wang, Xiaoyong Zhang, Xuhua Nong, Xinya Xu, Shuhua QiAbstract:Eight new chromones, engyodontiumones A–H (1–8), and three new phenol derivatives (9–11) together with eight known polyketides (12–19) were isolated from the deep-sea-derived fungus Engyodontium album DFFSCS021. Their structures were identified by extensive spectroscopic analysis. Compounds 8 and 16 showed significant selective cytotoxicity against human histiocytic lymphoma U937 Cell line with IC50 values of 4.9 and 8.8 μM, respectively. In addition, this is the first time to report that 8, 15 and 16 had mild antibacterial activity against Escherichia coli and Bacillus subtilis, and 15 showed potent antilarval activity against barnacle Balanus amphitrite larval settlement.
