6,516 research outputs found

    Yc-1, a Novel Activator of Platelet Guanylate Cyclase

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      YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] inhibited the aggregation of and ATP release from washed rabbit platelets induced by arachidonic acid (AA), collagen, U46619, platelet-activating factor (PAF), and thrombin in a concentration-dependent manner. YC-1 also disaggregated the clumped ptatelets caused by these inducers. The thromboxane B2 formation caused by collagen, PAF, and thrombin was inhibited by concentrations of YC-1 that did not affect formation of thromboxane B2 and prostaglandin D2 caused by AA. YG-1 suppressed the increase of intracellular Ca2+ concentration and generation of inositol 1,4,5- trisphosphate caused by these five aggregation inducers. Both the cAMP and cGMP contents of platelets were increased by YC-1 in a concentration- and time-dependent manner. Like sodium nitroprusside, YC-1 potentiated formation of cAMP caused by prostaglandin E, but not that by 3-isobutyl-1- methylxan- thine. Adenylate cyclase and cAMP phosphodiesterase activities were not altered by YC-1. Activities of granylate cyclase in platelet homogenate and cytosolic fraction were activated by YC-1, whereas particulate guanylate cyclase activity was unaffected. The antiplatelet effect of sodium nitroprusside but not that of YC-1 was blocked by hemoglobin and potentiated by superoxide dismutase. After intraperitoneal administration for 30 minutes, YC-1 prolonged the tail bleeding time of conscious mice. These data indicate that YC_1 is a direct soluble guanylate cyclase activator in rabbit platelets. It may also possess antithrombotic potential in vivo.#0996

    Studies of beef performance traits in Piemontese x Nanyang crossbred using microsatellites as genetic markers

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    Five microsatellites, IDVGA-2, IDVGA-27, IDVGA-46, IDVGA-55 and TGLA-44 were associated to beef performance traits of 100 heads of Nanyang cattle, Piemontese and their hybrid cattle using general linear model (GLM) with statistical analysis system (SAS). For microsatellite IDVGA-27, allele 136 had a positive relation with heart girth, height at hip cross and chest depth (body measurements) and loin width (muscularity evaluation); however, allele 142 showed a significant negative correlation with above performance traits. For IDVGA-46, the individuals with allele 205 had a good muscular development at loin width, on the contrary, the allele 211, which was not found in Piemontese cattle, had a negative correlation with shoulder development. Allele 203 (IDVGA-55) had a positive association with body measurement parameters including wither height, body length, height at hip cross and rump width

    YC-1 induces lipid droplet formation in RAW 264.7 macrophages

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    Background: 3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) is a potential anticancer drug that may activate soluble guanylyl cyclase (sGC) and increase the level of cyclic guanosine monophosphate (cGMP). The aim of this study was to explore the effects of YC-1 on lipid droplet accumulation and foam cell formation in macrophages. Results: Human-oxidized low density lipoprotein (ox-LDL) was used to induce accumulation of lipid droplets in a murine macrophage cell line, RAW 264.7. Oil red O staining showed that treatment with 20 mu M YC-1 for 24 h increased the area of intracellular lipid droplets in macrophages. The results of high content screening (HCS) with the AdipoRed (TM) assay further revealed that YC-1 enhanced ox-LDL-induced foam cell formation. This was evidenced by an increase in the total area of lipid droplets and the mean fluorescence intensity per cell. Inhibition of cGMP-dependent protein kinase (PKG) using KT5823 significantly reduced YC-1-enhanced lipid droplet formation in ox-LDL-induced macrophage foam cells. Conclusion: YC-1 induces lipid droplet formation in macrophages, possibly through the sGC/cGMP/PKG signaling pathway. This chemical should be tested with caution in future clinical trials
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