329 research outputs found

    ヒトPRE-Bリンパ腫細胞株RC-K8におけるBeraprost(a stable analogue of prostacyclin)によるuPA産生抑制効果

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    Plasminogen activation by urokinase-type plasminogen activator (uPA) is implicated in tumor invasion and metastasis by the breakdown of extracellular matrix.We have recently demonstrated the inhibitory effect of cAMP on uPA gene transcription in RC-K8 human lymphoma cells.Prostacyclin produced by endothelial cells is shown to increase cellular cAMP levels by activating adenylate cyclase.We, therefore, examined the effect of a stable analogue of prostacyclin, Beraprost, on uPA production in RC-K8 cells.uPA activity gradually increased in the conditioned medium with time.Beraprost (0.1 nM-1.0μM) inhibited uPA accumulation in a dose-dependent manner without affecting cell viability.High and low molecular forms of uPA were present in the conditioned medium, but no PA inhibitor was demonstrated by fibrin zymography.All forms of uPA decreased after Beraprost-treatment.Northern blot analysis revealed that after exposure to Beraprost, uPA mRNA levels increased transiently and then rapidly decreased to below control levels. Treatment with Beraprost resulted in a rapid activation of cellular cyclic AMP-dependent protein kinase (PKA).Beraprost completely negated uPA gene expression induced by phorbol myristate acetate, an activator of protein kinase C(PKC).These results suggest that Beraprost inhibits uPA production by suppressing uPA gene expression may be through the PKA pathway and that PKA-mediated signals are dominant in uPA gene expression as compared to those medicated by PKC. This inhibition of uPA expression by a prostacyclin analogue may be an important fact to explain the mechanism of antimetastatic effects of prostacyclin.富山医科薬科大学・博士(医学)・乙第310号・野村直樹・1996/2/28富山医科薬科大

    Polar Antiferromagnets Produced with Orbital-Order

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    Polar magnetic states are realized in pseudocubic manganite thin films fabricated on high-index substrates, in which a Jahn-Teller (JT) distortion remains an active variable. Several types of orbital-orders were found to develop large optical second harmonic generation, signaling broken-inversion-symmetry distinct from their bulk forms and films on (100) substrates. The observed symmetry-lifting and first-principles calculation both indicate that the modified JT q2 mode drives Mn-site off-centering upon orbital order, leading to the possible cooperation of "Mn-site polarization" and magnetism.Comment: 5 pages, 4 figure

    Differential responses of normal human coronary artery endothelial cells against multiple cytokines comparatively assessed by gene expression profiles

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    AbstractEndothelial cells play an important role in terms of biological functions by responding to a variety of stimuli in the blood. However, little is known about the molecular mechanism involved in rendering the variety in the cellular response. To investigate the variety of the cellular responses against exogenous stimuli at the gene expression level, we attempted to describe the cellular responses with comprehensive gene expression profiles, dissect them into multiple response patterns, and characterize the response patterns according to the information accumulated so far on the genes included in the patterns. We comparatively analyzed in parallel the gene expression profiles obtained with DNA microarrays from normal human coronary artery endothelial cells (HCAECs) stimulated with multiple cytokines, interleukin-1β, tumor necrosis factor-α, interferon-β, interferon-γ, and oncostatin M, which are profoundly involved in various functional responses of endothelial cells. These analyses revealed that the cellular responses of HCAECs against these cytokines included at least 15 response patterns specific to a single cytokine or common to multiple cytokines. Moreover, we statistically extracted genes contained within the individual response patterns and characterized the response patterns with the genes referring to the previously accumulated findings including the biological process defined by the Gene Ontology Consortium (GO). Out of the 15 response patterns in which at least one gene was successfully extracted through the statistical approach, 11 response patterns were differentially characterized by representing the number of genes contained in individual criteria of the biological process in the GO only. The approach to dissect cellular responses into response patterns and to characterize the pattern at the gene expression level may contribute to the gaining of insight for untangling the diversity of cellular functions
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