检索结果-内蒙古大学图书馆

Loss of the eP₂ prostaglandin e₂ receptor in immortalized human keratinocytes results in increased invasiveness and decreased paxillin expression

引用

AMeRICAN JOURNAL OF PATHOLOGY 2002年第6期161卷 2065-2078页

作者： Konger, RL Scott, GA Landt, Y Ladenson, JH Pentland, AP Indiana Univ Sch Med Dept Pathol & Lab Med Indianapolis IN 46202 USA Univ Rochester Sch Med & Dent Dept Dermatol Rochester NY 14642 USA Washington Univ Sch Med Div Lab Med St Louis MO USA

Prostaglandin e-2 (PGe(2)) receptor subtype eP2, which is coupled to cAMP metabolism, is known to mediate proliferation of primary human keratinocytes in vitro. The effect of gain or loss of eP2 receptors in immortalized human keratinocytes;(HaCat cells) was examined. HaCat keratinocytes were transfected with sense or anti-sense constructs of the eP2 receptor. Loss or gain of eP2 expression was documented by immunoblot and associated changes in agonist-stimulated cAMP production. Loss or gain of eP2 receptor expression correlated with alterations in plating efficiencies but with modest affects on growth. When cell lines were studied in an organ culture model, antisense clones were highly invasive compared with vector controls and sense transfectants. A marked increase in prostaglandin production is commonly seen in malignant lesions. Because prostaglandin receptors are known to undergo ligand-induced receptor down-regulation, we sought to determine whether eP2 receptor down-regulation results in increased invasiveness. In vector controls, invasiveness was reproduced by ligand-dependent eP2 receptor down-regulation as assessed by immunohistochemistry. in addition, loss of eP2 receptor expression was associated with decreased paxillin expression, a critical component of focal adhesion assembly. Thus, down-regulation of eP2 receptors represents a potential mechanism for neoplastic progression to an invasive phenotype.

关键词：前列地尔/类似物和衍生物前列地尔/代谢抗体单克隆/代谢细胞系细胞大小细胞转化肿瘤环AMP/代谢细胞支架蛋白质类/代谢 DNA 反义/代谢减量调节/生理学成纤维细胞/细胞学成纤维细胞/代谢遗传载体角蛋白细胞/细胞学角蛋白细胞/代谢桩蛋白表型磷蛋白类/代谢受体前列腺素e/遗传学受体前列腺素e/代谢皮肤/细胞学皮肤/代谢动物人类

来源：评论

学校读者我要写书评

暂无评论

Prostaglandin e₂ receptors, eP2 and eP4, differentially modulate TNF-α and IL-6 production induced by lipopolysaccharide in mouse peritoneal neutrophils

引用

BIOCHeMICAL AND BIOPHYSICAL ReSeARCH COMMUNICATIONS 2000年第1期278卷 224-228页

作者： Yamane, H Sugimoto, Y Tanaka, S Ichikawa, A Kyoto Univ Grad Sch Pharmaceut Sci Dept Physiol Chem Sakyo Ku Kyoto 6068501 Japan

The expression and function of prostaglandin (PG) e-2 receptors were examined in mouse neutrophils exudated into the peritoneal cavity by casein treatment. expressions of the eP2 and eP4 receptors were detected in neutrophils by Northern blot, but those of eP1 and eP3 receptors were not detected by RT-PCR. eP2-selective agonist, ONO-Ae1-259, and eP4-selective agonist, ONO-Ae1-329, stimulated cAMP formation in the cells. PGe(2) affected the TNF-alpha and IL-6 production in lipopolysaccharide (LPS)-treated neutrophils;it suppressed the TNF-alpha production and enhanced the IL-6 production. The PGe(2) effects were mimicked by dibutyryl cAMP. This is the first study of the enhancement of IL-6 production by cAMP-elevating reagents in neutrophils. Using neutrophils from eP2- and eP4-deficient mice in combination with eP2- and eP4-selective agonists, it was found that the augmentation of IL-6 was mediated mainly by the eP2 receptor and the suppression of TNF-alpha by the eP4 receptor and partially by the eP2 receptor. These findings indicate that casein-induced peritoneal neutrophils express Gs-coupled PGe, receptors, eP2 and eP4, which might differentially regulate the LPS-induced production of TNF-alpha and IL-6. (C) 2000 Academic Press.

关键词：印迹法 RNA 布拉地新/药理学酪蛋白类/药理学环AMP/代谢细胞因子类/生物合成剂量效应关系药物白细胞介素6/生物合成脂多糖类/药理学小鼠近交C57BL 中性白细胞/代谢腹膜/代谢受体前列腺素/代谢受体前列腺素e/激动剂受体前列腺素e/代谢逆转录聚合酶链反应时间因素肿瘤坏死因子α/生物合成动物男(雄)性小鼠

来源：评论

学校读者我要写书评

暂无评论

Impaired bone resorption to prostaglandin e₂ in prostaglandin e receptor eP4-knockout mice

引用

JOURNAL OF BIOLOGICAL CHeMISTRY 2000年第26期275卷 19819-19823页

作者： Miyaura, C Inada, M Suzawa, T Sugimoto, Y Ushikubi, F Ichikawa, A Narumiya, S Suda, T Showa Univ Sch Dent Dept Biochem Shinagawa Ku Tokyo 1428555 Japan Kyoto Univ Fac Pharmaceut Sci Dept Physiol Chem Kyoto 6068501 Japan Kyoto Univ Fac Med Dept Pharmacol Kyoto 6068501 Japan Tokyo Univ Pharm & Life Sci Sch Pharm Dept Biochem Tokyo 1920392 Japan

Prostaglandin e-2 (PGe(2)) acts as a potent stimulator of bone resorption. In this study, we first clarified in normal ddy mice the involvement of protein kinase A and induction of matrix metalloproteinases (MMPs) in PGe(2)-induced bone resorption, and then identified PGe receptor subtype(s) mediating this PGe(2) action using mice lacking each subtype (eP1, eP2, eP3, and eP4) of PGe receptor. In calvarial culture obtained from normal ddy mice, both PGe(2) and dibutyryl cyclic AMP (Bt(2)cAMP) stimulated bone resorption and induced MMPs including MMP-2 and MMP-13. Addition of an inhibitor of protein kinase A, H89, or an inhibitor of MMPs, BB94, significantly suppressed bone-resorbing activity induced by PGe(2). In calvarial culture from eP1-, eP2-, and eP3-knockout mice, PGe(2) stimulated bone resorption to an extent similar to that found in calvaria from the wild-type mice. On the other hand, a marked reduction in bone resorption to PGe(2) was found in the calvarial culture from eP4-knockout mice. The impaired bone resorption to PGe(2) was also detected in long bone cultures from eP4-knockout mice. Bt(2)cAMP greatly stimulated bone resorption similarly in both wild-type and eP4-knockout mice. Induction of MMP-2 and MMP-13 by PGe(2) was greatly impaired in calvarial culture from eP4-knockout mice, but Bt(2)cAMP stimulated MMPs induction similarly in the wild-type and eP4-knockout mice. These findings suggest that PGe(2) stimulates bone resorption by a cAMP-dependent mechanism via the eP4 receptor.

关键词：动物新生印迹法 RNA 印迹法蛋白质骨质吸收/遗传学布拉地新/代谢细胞培养的胶原酶类/代谢地诺前列酮/代谢剂量效应关系药物明胶酶类/代谢基因型小鼠基因敲除聚合酶链反应受体前列腺素e/遗传学受体前列腺素e/代谢受体前列腺素e/生理学信号传导/遗传学颅骨/代谢动物小鼠

来源：评论

学校读者我要写书评

暂无评论

Characterization of prostaglandin e₂ receptors and their role in 24,25-(OH)₂D₃-mediated effects on resting zone chondrocytes

引用

JOURNAL OF CeLLULAR PHYSIOLOGY 2000年第2期182卷 196-208页

作者： Del Toro, F Sylvia, VL Schubkegel, SR Campos, R Dean, DD Boyan, BD Schwartz, Z Univ Texas Hlth Sci Ctr Dept Orthopaed San Antonio TX 78284 USA Univ Texas Hlth Sci Ctr Dept Orthodont San Antonio TX 78284 USA Univ Texas Hlth Sci Ctr Dept Periodont San Antonio TX 78284 USA Univ Texas Hlth Sci Ctr Dept Biochem San Antonio TX 78284 USA Wilford Hall USAF Med Ctr Dept Periodont San Antonio TX 78236 USA Hebrew Univ Jerusalem Jerusalem Israel

Resting zone chondrocyte differentiation is modulated by the vitamin D meabolite, 24,25-(OH)(2)D-3, via activation of protein kinase C (PKC). In previous studies, inhibition of prostaglandin production with indomethacin caused an increase in PKC activity, suggesting that changes in prostaglandin levels may mediate the 24,25-(OH)(2)D-3-dependent response and act as autocrine or paracrine regulators of chandrocyte metabolism. Supporting this hypothesis is the fact that resting zone cells respond directly to prostaglandin e-2 (PCe2). The aim of the present study was to identify which PGe, receptor subtypes (eP) mediate the effects of PGe, on resting zone cells. Using primers specific for eP1-eP4, reverse transcription-polymerase chain reaction (RT-PCR) amplified eP1 and eP2 cDNA in a RT-dependent manner. A variant form of the eP1 cDNA, ePIv, was also amplified in an RT-dependent manner. In parallel experiments, we used eP subtype-specific agonists to examine the role of eP receptors in 24,25-(OH),D,mediated cell proliferation and differentiation. 17-phenyl-trinor-PGe(2) (PTPGe(2)), an eP1 agonist, increased [H-3]-thymidine incorporation in a dose-dependent manner and reversed the 24,25-(OH)(2)D-2-induced inhibition of [H-3]-thymidine incorporation. SC-19220, an eP1 antagonist, caused a further dose-dependent decrease in 24,25-(OH)(2)D-2-induced inhibition of [H-3]-thymidine incorporation. PTPGe(2) also caused a biphasic increase in [S-35]-sulfate incorporation and increased alkaline phosphatase enzyme activity at high concentrations (10(-8) M). 24,25-(OH)(2)D-3-induced alkaline phosphatase activity was synergistically stimulated in a dose-dependent manner by PTPGe(2). In contrast, 24,25-(OH)(2)D-3 induced PKC activity was inhibited in a dose-dependent manner by PTPGe, and SC-1 9220, the eP1 antagonist, elevated PKC activity at high concentrations (10-8 M). The eP2 agonist, misoprostol, only affected [S-35]-sulfate incorporation, but in a dose-dependent manner. The eP3

关键词： 24 25-二羟维生素D3/药理学碱性磷酸酶/代谢细胞培养的软骨细胞/药物作用软骨细胞/代谢蛋白质亚型/激动剂蛋白质亚型/遗传学蛋白质亚型/代谢蛋白质亚型/生理学蛋白激酶C/代谢蛋白聚糖类/代谢 RNA 信使/代谢大鼠 Sprague-Dawley 受体前列腺素e/激动剂受体前列腺素e/遗传学受体前列腺素e/代谢受体前列腺素e/生理学硫酸盐类/代谢胸苷/代谢动物男(雄)性大鼠

来源：评论

学校读者我要写书评

暂无评论

Prostanoid receptors in intestinal epithelium: selective expression, function, and change with inflammation

引用

PROSTAGLANDINS LeUKOTRIeNeS AND eSSeNTIAL FATTY ACIDS 2000年第4期63卷 223-235页

作者： Takafuji, V Cosme, R Lublin, D Lynch, K Roche, JK Univ Virginia Hlth Sci Ctr Dept Internal Med Charlottesville VA 22908 USA Univ Virginia Hlth Sci Ctr Dept Pharmacol Charlottesville VA 22908 USA

The tissue concentration of PGe(2) is heightened during mucosal inflammation. Nevertheless, the cellular targets of this prostanoid and its effects on epithelial cell physiology are incompletely understood. We used a panel of specific immunoglobulin and mRNA probes in order to localize and quantitate the four member eP family of prostanoid receptors for binding PGe(2) on cells of histologically normal and inflamed human colonic mucosa, and then examined the physiological consequences for the epithelial component of intestine, with special attention to its barrier function. Prostanoid receptors were selectively expressed on a limited number of human colonic mucosal cells, and differed markedly between normal and inflamed tissue, in non-inflamed mucosa, eP2 and eP3 were expressed on epithelia at the apex of crypts;while eP4 was expressed on surface and lateral crypt epithelia. Dual immunostaining and in situ hybridization with digoxygenin-labelled RNA probes largely confirmed the epithelial localization of eP4. On the other hand, during inflammation, lateral crypt (non-surface) epithelial cells newly and significantly expressed prostanoid receptors eP2 and eP3 (p < 0.05, by computer-assisted densitometry). Functionally, exogenous e series prostanoids applied to epithelial monolayers in nM concentrations brought about a 24% increase in the level of barrier function;an associated rise in intracellular cAMP (eC50 of 281);and protection of epithelium from the effects of T cell cytokines. A major perturbation in the number and distribution of functional eicosonoid receptors on epithelia occurs in chronic inflammation of human colonic mucosa. (C) 2000 Harcourt Publishers Ltd.

关键词：前列地尔/药理学抗体/免疫学抗体特异性共同培养技术环AMP/代谢地诺前列酮/药理学电生理学上皮细胞/细胞学上皮细胞/药物作用上皮细胞/代谢上皮细胞/病理学免疫组织化学原位杂交炎症/遗传学炎症/代谢干扰素Ⅱ型/药理学肠黏膜/细胞学肠黏膜/药物作用肠黏膜/代谢肠黏膜/病理学 RNA 信使/遗传学 RNA 信使/代谢受体前列腺素e/分类受体前列腺素e/遗传学受体前列腺素e/免疫学受体前列腺素e/代谢 T淋巴细胞/代谢紧密连接部/药物作用紧密连接部/代谢紧密连接部/病理学人类

来源：评论

学校读者我要写书评

暂无评论

New pieces for the puzzle: Nonsteroidal anti-inflammatory drugs and corneal ulcers

引用

JOURNAL OF CATARACT AND ReFRACTIVe SURGeRY 2000年第9期26卷 1263-1265页

作者： Price, FW

来源：评论

学校读者我要写书评

暂无评论

New class of biphenylene dibenzazocinones as potent ligands for the human eP₁ prostanoid receptor

引用

BIOORGANIC & MeDICINAL CHeMISTRY LeTTeRS 1999年第18期9卷 2699-2704页

作者： Ruel, R Lacombe, P Abramovitz, M Godbout, C Lamontagne, S Rochette, C Sawyer, N Stocco, R Tremblay, NM Metters, KM Labelle, M Merck Frosst Ctr Therapeut Res Pointe Claire PQ H9R 4P8 Canada

A new class of potent and selective ligands for the human ePI prostanoid receptor is described. SAR studies reported herein allowed the identification of several potent dibenzazocinones bearing an acylsulfonamide side chain. The binding affinity of these compounds on all eight human prostanoid receptors is reported. (C) 1999 Published by elsevier Science Ltd. All rights reserved.

关键词：吖辛因类/化学吖辛因类/代谢吖辛因类/药理学联苯化合物/化学联苯化合物/代谢联苯化合物/药理学配体蛋白质结合受体前列腺素e/药物作用受体前列腺素e/代谢受体前列腺素e eP1亚型构效关系人类

来源：评论

学校读者我要写书评

暂无评论

Prostaglandin e-prostanoid-3 receptor activation of cyclic AMP response element-mediated gene transcription

引用

JOURNAL OF PHARMACOLOGY AND eXPeRIMeNTAL THeRAPeUTICS 1999年第1期289卷 140-148页

作者： Audoly, LP Ma, LJ Feoktistov, I De Foe, SK Breyer, MD Breyer, RM Vanderbilt Univ Dept Med Div Nephrol Nashville TN 37323 USA Vanderbilt Univ Dept Med Div Cardiol Nashville TN 37323 USA Vanderbilt Univ Dept Pharmacol Nashville TN 37323 USA Vanderbilt Univ Dept Mol Physiol & Biophys Nashville TN 37323 USA Vanderbilt Univ Vet Adm Med Ctr Nashville TN 37323 USA Vanderbilt Univ Sch Med Nashville TN 37323 USA

The prostaglandin e-prostanoid (eP), receptor signals primarily through the inhibitory G protein G(i), thereby decreasing intracellular cAMP levels. To study the signal transduction properties of the rabbit eP3 receptor, five splice variants were expressed in HeK293tsA201 cells: 72A, 74A, 77A, 80A and the novel splice Variant NT, which lacks the C-terminal sequence. The ability of the eP3 receptor splice variants to modulate expression of a beta-galactosidase reporter gene under the control of a promoter containing cAMP response elements (CRe) was assessed. each splice variant induced sulprostone-mediated increase in beta-gatactosidase enzymatic activity with eC50 ranging from 0.8 nM for the NT splice variant to 3.1 nM for the 77A splice variant. Substitution of either Asp(338) with Ala, or Arg(329) with Ala or Glu in the 77A splice variant resulted in a loss of receptor-evoked increases in P-galactosidase activity, whereas substitution of Lys(300) with alanine had no effect on signal transduction. These phenotypes correlate with the inhibition of cAMP generation by direct cAMP measurement. Signal transduction was insensitive to pretreatment of cells with pertussis toxin, suggesting that a nonG(i)/G(o) pathway is activated by the eP3 receptor. Direct measurement of second messenger levels confirmed that there was no increase in cAMP levels mediated by the 77A splice variant, however, there was a modest increase in intracellular Ca2+. Partial blockade of the reporter activity with kinase inhibitors demonstrates that CRe activation is mediated in part by a Ca2+-dependent kinase pathway. These data suggest that the eP, receptor signals through a novel cAMP response element binding protein/CRe pathway.

关键词：选择性剪接氨基酸序列钙/代谢细胞系环AMP/遗传学环AMP/代谢酶联免疫吸附测定基因表达调控酶学基因报告分子序列数据受体前列腺素e/遗传学受体前列腺素e/代谢反应元件/遗传学反应元件/生理学信号传导/生理学转录遗传/生理学转染 β半乳糖苷酶类/遗传学 β半乳糖苷酶类/代谢动物女(雌)性兔

来源：评论

学校读者我要写书评

暂无评论

Prostaglandin e₂ mediates inhibition of insulin secretion by interleukin-1β

引用

JOURNAL OF BIOLOGICAL CHeMISTRY 1999年第44期274卷 31245-31248页

作者： Tran, POT Gleason, Ce Poitout, V Robertson, RP Pacific NW Res Inst Seattle WA 98122 USA Univ Washington Dept Med & Pharmacol Seattle WA 98122 USA

Interleukin-1 beta (IL-1 beta) and prostaglandin e-2 (PGe(2)), frequently co-participants in inflammatory states, are two well recognized inhibitors of glucose-induced insulin secretion. Previous reports have concluded that the inhibitory effects of these two autacoids on pancreatic beta cell function are not related because indomethacin, a potent prostaglandin synthesis inhibitor, does not prevent IL-1 beta effects. However, indomethacin is not a specific cyclooxygenase inhibitor, and its other pharmacologic effects are likely to inhibit insulin secretion independently. Since we recently observed that IL-1 beta induces cyclooxygenase-2 (COX-2) gene expression and PGe(2) synthesis in islet beta cells, we have reassessed the possibility that PGe(2) mediates IL-1 beta effects on beta function. By using two cell lines (HIT-T15 and beta HC13) as well as Wistar rat isolated pancreatic islets, we examined the ability of two COX-2-specific antagonists, NS-398 and SC-236, to prevent IL-1 beta inhibition of insulin secretion. Both drugs prevented IL-1 beta from inducing PGe(2) synthesis and inhibiting insulin secretion;adding back exogenous PGe(2) re-established inhibition of insulin secretion in the presence of IL-1 beta. We also found that eP3, the PGe(2) receptor subtype whose post-receptor effect is to decrease adenylyl cyclase activity and, thereby, insulin secretion, is the dominant mRNA subtype expressed. We conclude that endogenous PGe(2) mediates the inhibitory effects of exogenous IL-1 beta on beta cell function.

关键词：环氧化酶2 环氧化酶2抑制剂环加氧酶抑制药地诺前列酮/代谢葡萄糖/药理学胰岛素/代谢白细胞介素1/药理学胰岛/代谢同工酶类/代谢硝基苯甲酸盐/药理学前列腺素内过氧化物合酶类/代谢吡唑类/药理学大鼠 Wistar 受体前列腺素e/代谢受体前列腺素e eP3亚型磺胺类/药理学动物男(雄)性大鼠

来源：评论

学校读者我要写书评

暂无评论

The key amino acid residue of prostaglandin eP3 receptor for governing G protein association and activation steps

引用

BIOCHeMICAL AND BIOPHYSICAL ReSeARCH COMMUNICATIONS 1999年第1期255卷 164-168页

作者： Satoh, S Chang, CS Katoh, H Hasegawa, H Nakamura, K Aoki, J Fujita, H Ichikawa, A Negishi, M Kyoto Univ Fac Pharmaceut Sci Dept Mol Neurobiol Sakyo Ku Kyoto 6068501 Japan Kyoto Univ Fac Pharmaceut Sci Dept Physiol Chem Sakyo Ku Kyoto 6068501 Japan

To assess the role of the conserved DPWXY motif of the seventh transmembrane domain in prostanoid receptor-mediated G protein activation, we have mutated the negatively charged Asp-318 in this motif of the Gi-coupled mouse prostaglandin eP3 receptor to uncharged but polar Asn (eP3-D318N) and to the nonpolar Leu (eP3-D318L). The eP3 agonist and antagonist showed similar binding affinities for the mild-type and two mutant receptors. The wild-type and eP3-D318N receptors but not eP3-D318L receptor associated with Gi in guanine nucleotide- and pertussis toxin-sensitive manners. On the other hand, the wild-type receptor but not two mutant receptors had the ability to stimulate GTPase activity and to inhibit the adenylate cyclase. These findings demonstrate that the chemical nature of the amino acid residue at position 318 of the seventh transmembrane domain of the eP3 receptor dissociates the step of Gi association from that of subsequent Gi activation in the process of the eP3 receptor-Gi coupling (C) 1999 Academic Press.

关键词：氨基酸类/遗传学氨基酸类/代谢结合部位/遗传学 CHO细胞仓鼠亚科 GTP结合蛋白质类/遗传学 GTP结合蛋白质类/代谢突变受体前列腺素e/遗传学受体前列腺素e/代谢受体前列腺素e eP3亚型信号传导动物小鼠

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：