4,057 research outputs found
Yc-1 Inhibits Proliferation of Human Vascular Endothelial Cells through a Cyclic Gmp-Independent Pathway
No full textThis study was designed to investigate the effect of YC-1, 3 -(5'- hydroxymethyl-2'-furyl)-1-benzylindazole, in human umbilical vein endothelial cells (HUVECs) proliferation and its underlying mechanism. YC- 1 at a range of concentrations( 5-50 muM) inhibited DNA synthesis and decreased cell number in cultured HUVEC in a dose- and time-dependent manner. YC- 1 was not cytotoxic at these concentrations. [H-3]thymidine incorporation and flow cytometry analyses revealed that YC-1 treatment decreased DNA synthesis and arrested the cells at the G0/G1 phase of the cell cycle. Western blot analysis demonstrated that YC-1 (5-50 muM) increased the levels of cyclin-dependent kinase (CDK)-inhibitory proteins (CKIs), p 21 and p27, but did not induce any significant changes of cyclins and CDKs. In the YC-1-treated HUVEC, the formation of CDK2-p21 complex, but not CDK2-p27 complex, was increased and the assayable CDK2 kinase activity was decreased. These changes were in a dose-dependent manner. In contrast, the formations of CDK4-p21 and CDK4-p27 complex were slightly increased and the assayable CDK4 kinase activity was slightly decreased (if there were any changes). Pretreatment with guanylyl cyclase inhibitors, 1H-(1,2,4)oxadiazolo[4,3- a]quinozalin-1-one (ODQ) and methylene blue, inhibited the YC-1-induced increase of cyclic GMP level, but did not change significantly the magnitude of the YC-1-induced inhibition of thymidine incorporation and cell number in HUVEC. These results indicate that YC-1-induced cell cycle arrest in HUVEC occurred when the cyclin-CDK system was inhibited just as p21 and p27 protein levels were augmented. This YC-1-induced antiproliferation effect in HUVEC is via acyclic GMP-independent pathway
Inhibitory Mechanisms of Yc-1 and Pmc in the Induction of Inos Expression by Lipoteichoic Acid in Raw 264.7 Macrophages
No full textIn the present study, the signal pathways involved in NO formation and iNOS expression in RAW 264.7 macrophages stimulated by LTA were investigated. We also compared the relative inhibitory activities and mechanisms of PMC, a novel potent antioxidant of alpha-tocopherol derivatives, with those of YC-1, an sGC activator, on the induction of iNOS expression by LTA in cultured macrophages ill vitro and LTA-induced hypotension ill vivo. LTA induced concentration (0.1-50 mug/mL)- and time (4-24 hr)-dependent increases in nitrite (an indicator of NO biosynthesis) in macrophages. Both PMC (50 muM) and YC-1 (10 muM) inhibited NO production, iNOS protein, mRNA expression, and IkappaBalpha degradation upon stimulation by LTA (20 mug/mL) in macrophages. On the other hand, PMC (50 muM) almost completely suppressed JNK/ SAPK activation, whereas YC-1 (10 muM) only partially inhibited its activation in LTA-stimulated macrophages. Moreover, PMC (10 mg/kg, i.v.) and YC-1 (5 mg/kg, i.v.) significantly inhibited the fall in MA-P stimulated by LTA ( 10 mg/kg, i.v .) in rats. In conclusion, we demonstrate that YC-1 shows more-potent activity than PMC at abrogating the expression of iNOS in macrophages in vitro and reversing delayed hypotension in rats with endotoxic shock stimulated by LTA. The inhibitory mechanisms of PMC may be due to its antioxidative properties, with a resulting influence on JNK/ SAPK and NF- kappaB activations. YC-1 may be mediated by increasing cyclic GMP, followed by, at least partly, inhibition of JNK/SAPK and NF-kappaB activations, thereby leading to inhibition of iNOS expression. (C) 2004 Elsevier Inc. All rights reserved
Clinical manifestations and molecular epidemiology of necrotizing pneumonia and empyema caused by Streptococcus pneumoniae in children in Taiwan.
No full textYc-1 Inhibits Hif-1 Expression in Prostate Cancer Cells: Contribution of Akt/Nf-Kappa B Signaling to Hif-1 Alpha Accumulation during Hypoxia
No full textHypoxia-inducible factor 1 ( HIF-1), a transcription factor that is critical for tumor adaptation to microenvironmental stimuli, represents an attractive chemotherapeutic target. YC-1 is a novel antitumor agent that inhibits HIF-1 through previously unexplained mechanisms. In the present study, YC- 1 was found to prevent HIF-1 alpha and HIF-1 beta accumulation in response to hypoxia or mitogen treatment in PC-3 prostate cancer cells. Neither HIF-1 alpha protein half -life nor mRNA level was affected by YC- 1. However, YC-1 was found to suppress the PI3K/Akt/mTOR/4E-BP pathway, which serves to regulate HIF-1 alpha expression at the translational step. We demonstrated that YC-1 also inhibited hypoxia-induced activation of nuclear factor ( NF)-kappa B, a downstream target of Akt. Two modulators of the Akt/NF- kappa B pathway, caffeic acid phenethyl ester and evodiamine , were observed to decrease HIF-1 alpha expression. Additionally, overexpression of NF-kappa B partly reversed the ability of wortmannin to inhibit HIF-1 alpha-dependent transcriptional activity, suggesting that NF-kappa B contributes to Akt-mediated HIF-1 alpha accumulation during hypoxia. Overall, we identify a potential molecular mechanism whereby YC-1 serves to reduce HIF-1 expression
Effect of the antitryptic activity of rice bran on growth, feed efficiency and residual tryptic activity in the intestinal content and feces of the rat.(in Chinese)
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Investigation of anticancer mechanism of clavulone II, a coral cyclopentenone prostaglandin analog, in human acute promyelocytic leukemia.
No full textExpression of the ipomoelin gene from sweet potato is regulated by dephosphorylated proteins, calcium ion and ethylene.
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