检索结果-内蒙古大学图书馆

Differential phospholipase D activation by bradykinin and sphingosine 1-phosphate in NIH 3T3 fibroblasts overexpressing gelsolin

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第39期274卷 27385-27391页

作者： Banno, Y Fujita, H Ono, Y Nakashima, S Ito, Y Kuzumaki, N Nozawa, Y Gifu Univ Sch Med Dept Biochem Gifu 500 Japan Hokkaido Univ Sch Med Inst Canc Mol Genet Lab Sapporo Hokkaido 0608638 Japan Kobe Univ Fac Sci Dept Biol Kobe Hyogo 657 Japan

Gelsolin, an actin-binding protein, shows a strong ability to bind to phosphatidylinositol 4,5-bisphosphate (PIP2). Here we showed in in vitro experiments that gelsolin inhibited recombinant phospholipase D1 (PLD1) and PLD2 activities but not the oleate-dependent PLD and that this inhibition was not reversed by increasing PIP2 concentration. To investigate the role of gelsolin in agonist-mediated PLD activation, we used NIH 3T3 fibroblasts stably transfected with the cDNA for human cytosolic gelsolin. Gelsolin overexpression suppressed bradykinin-induced activation of phospholipase C (PLC) and PLD. On the other hand, sphingosine 1-phosphate (S1P)-induced PLD activation could not be modified by gelsolin overexpression, whereas PLC activation was suppressed. PLD activation by phorbol myristate acetate or Ca2+ ionophore A23187 was not affected by gelsolin overexpression. Stimulation of control cells with either bradykinin or S1P caused translocation of protein kinase C (PKC) to the membranes. Translocation of PKC-alpha and PKC-beta 1 but not PKC-epsilon was reduced in gelsolin-overexpressed cells, whereas phosphorylation of mitogen-activated protein kinase was not changed. S1P-induced PLC activation and mitogen-activated protein kinase phosphorylation were sensitive to pertussis toxin, but PLD response was insensitive to such treatment, suggesting that S1P induced PLD activation via certain G protein distinct from G(i) for PLC and mitogen-activated protein kinase pathway. Our results suggest that gelsolin modulates bradykinin-mediated PLD activation via suppression of PLC and PKC activities but did not affect S1P-mediated PLD activation.

关键词： 3T3细胞缓激肽/药理学卡西霉素/药理学细胞膜/酶学 DNA 互补依他酸/药理学酶激活钙结合微丝蛋白/遗传学钙结合微丝蛋白/代谢同工酶类/代谢动力学溶血磷脂素类丝裂原激活蛋白激酶类/代谢百白咳毒素磷脂酰肌醇4 5-二磷酸/药理学磷脂酶D/代谢蛋白激酶C/代谢蛋白激酶Cα 蛋白激酶Cε 重组蛋白质类/代谢鞘氨醇/类似物和衍生物鞘氨醇/药理学十四酰佛波乙酯/药理学转染 C型磷脂酶类/代谢毒力因子鲍特菌属/药理学动物人类小鼠

来源：评论

学校读者我要写书评

暂无评论

Sphingosine 1-phosphate induces angiogenesis: Its angiogenic action and signaling mechanism in human umbilical vein endothelial cells

引用

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 1999年第3期264卷 743-750页

作者： Lee, OH Kim, YM Lee, YM Moon, EJ Lee, DJ Kim, JH Kim, KW Kwon, YG Hallym Univ Inst Environm & Life Sci Chunchon 200702 Kangwon Do South Korea Hallym Univ Hallym Acad Sci Chunchon 200702 Kangwon Do South Korea Pusan Natl Univ Dept Mol Biol Pusan 609735 South Korea Kwang Ju Inst Sci & Technol Dept Life Sci Kwangju 500712 South Korea

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite abundantly stored in platelets and released upon platelet activation. Recently, S1P has been postulated for its potential roles in angiogenesis. In this study, me provided several lines of evidence showing that S1P has angiogenic activity. In vitro, S1P stimulated DNA synthesis and chemotactic motility of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, reaching a near maximum at 1 mu M. S1P also significantly induced tube formation of HUVECs on Matrigel. Matrigel plug assay in mice revealed that S1P promotes angiogenesis in vivo. In addition, exposure of HUVECs to S1P led to rapid activation of extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinase (p38 MAPK) in a pertussis toxin (PTX)-sensitive manner. Notably, HUVEC migration and tube formation in response to S1P were completely blocked by pretreatment with PTX, Further, the MEK inhibitor U0126 markedly inhibited S1P-induced tube formation but S1P-induced migration was not affected by inhibition of ERK and p38 MAPK. Taken together, these results indicate that S1P induces angiogenesis predominantly via G(i) protein-coupled receptors in endothelial cells and suggest that S1P may act as an important modulator of platelet-induced angiogenesis. (C) 1999 Academic Press.

关键词：细胞分裂/药物作用细胞运动/药物作用细胞培养的溶血磷脂素类 MAP激酶信号系统/生理学新生血管化生理性/药物作用信号传导/生理学鞘氨醇/类似物和衍生物鞘氨醇/药理学鞘氨醇/生理学动物人类小鼠

来源：评论

学校读者我要写书评

暂无评论

Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第1期275卷 288-296页

作者： An, SZ Zheng, YH Bleu, T Univ Calif San Francisco Dept Med San Francisco CA 94143 USA

Sphingosine l-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction. Contradictory reports propose that S1P acts as either an intracellular second messenger or an extracellular ligand for cell-surface receptors. Hence, the precise signaling mechanisms mediating the diverse cellular effects of S1P remain to be determined. Here, we investigate whether S1P stimulation of cell. proliferation, survival, and related signaling events can be mediated by the recently cloned Edg family members of G protein-coupled receptors. We observed that S1P treatment significantly increased proliferation of HTC4 hepatoma cells stably transfected with human S1P receptor Edg3 or Edg5, which was attributable to stimulation of cell growth and inhibition of apoptosis caused by serum starvation. Edg3 and Edg5 transduced S1P-evoked signaling events relevant to cell proliferation and survival, including activation of the ERK/MAP kinases, and immediate-early induction of c-Jun and c-Fos. Transcriptional activation of reporter genes for the c-fos promoter and the serum response element by Edg3 and Edg5 transfected in Jurkat cells was inhibited by pertussis toxin and C3 exoenzyme, implicating G(i/o)- and Rho-dependent pathways. Our data also indicated that Edg3 and Edg5 mediated the serum response element activation through transcriptional factors Elk-1 and serum response factor. Thus, specific G protein-coupled receptors Edg3 and Edg5 account for, at least in part, S1P-induced cell proliferation, survival, and related signaling events.

关键词：细胞分裂细胞存活克隆分子 DNA结合蛋白质类/代谢 GTP结合蛋白质α亚单位 Gi-Go GTP结合蛋白质类/代谢 I-κB蛋白质类溶血磷脂素类丝裂原活化蛋白激酶1/代谢丝裂原活化蛋白激酶3 丝裂原激活蛋白激酶类/代谢分子序列数据核蛋白质类/代谢原癌基因蛋白质类/代谢原癌基因蛋白质c-fos/代谢原癌基因蛋白质c-jun/代谢受体细胞表面/遗传学受体细胞表面/代谢受体 G-蛋白偶联受体溶血磷脂血清反应因子信号传导鞘氨醇/类似物和衍生物鞘氨醇/代谢转录因子AP-1/代谢转录因子 ets结构域蛋白Elk1 ρGTP结合蛋白质类/代谢人类

来源：评论

学校读者我要写书评

暂无评论

Involvement of sphingosine in mitochondria-dependent Fas-induced apoptosis of type II Jurkat T cells

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第21期275卷 15691-15700页

作者： Cuvillier, O Edsall, L Spiegel, S Georgetown Univ Med Ctr Dept Biochem & Mol Biol Washington DC 20007 USA

Exposure to anti-Fas antibody in Jurkat cells (type II cells), which are characterized by a weak caspase-8 activation at the death-inducing signaling complex (DISC), induced a biphasic increase in ceramide levels. The early generation of ceramide preceded transient activation of acidic ceramidase and subsequent production of sphingosine, followed by cytochrome c release, activation of caspases-2, -3, -6, -7, -8, and -9, Bid cleavage, and a later sustained ceramide accumulation. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone inhibited early increases of ceramide and sphingosine, whereas overexpression of Bcl-x(L), had no effect, and both prevented the later sustained ceramide accumulation. Exogenous sphingosine, as well as cell-permeable C-2-ceramide, induced cytochrome c release from mitochondria in a caspase-independent fashion leading to activation of caspase-9 and executioner caspases and, surprisingly, activation of the initiator caspase-8 and processing of its substrate Bid. These effects were also completely abolished by Bcl-x(L) overexpression. Our results suggest that sphingosine might also be involved in the mitochondria-mediated pathway of Fas-induced cell death in type II cells.

关键词：氨基酸氯甲基酮类/药理学抗体单克隆/药理学抗原 CD95/免疫学抗原 CD95/代谢细胞凋亡与BH3相互作用的凋亡激活蛋白质羧酸类/药理学载体蛋白质类/代谢半胱氨酸天冬氨酸蛋白酶/代谢神经酰胺类/代谢半胱氨酸蛋白酶抑制剂/药理学细胞色素c组/代谢酶激活伏马菌素类基因表达调控 Jurkat细胞线粒体/代谢寡肽类/药理学原癌基因蛋白质c-bcl-2/代谢鞘氨醇/类似物和衍生物鞘氨醇/代谢鞘氨醇/药理学转染 bcl-X蛋白质人类

来源：评论

学校读者我要写书评

暂无评论

Fusarium mycotoxins in corn and corn products in a high-risk area for gastric cancer in Shandong Province, China

引用

JOURNAL OF AOAC INTERNATIONAL 1999年第3期82卷 657-662页

作者： Groves, FD Zhang, LA Chang, YS Ross, PF Casper, H Norred, WP You, WC Fraumeni, JF NCI Div Canc Epidemiol & Genet Bethesda MD 20892 USA Beijing Inst Canc Res Beijing 100034 Peoples R China Anim & Plant Hlth Inspect Serv USDA Natl Vet Serv Labs Ames IA 50010 USA N Dakota State Univ Dept Vet & Microbiol Sci Fargo ND 58105 USA ARS USDA Russell Res Ctr Athens GA 30604 USA NCI Div Canc Epidemiol & Genet Bethesda MD 20892 USA

Consumption of fermented, but not unfermented, corn pancakes has been linked with elevated stomach cancer mortality rates in rural Linqu County in Shandong Province, China. Previous surveys of fungal contamination of corn in China have detected fumonisins, which are mycotoxins produced by Fusarium moniliforme. To determine whether mycotoxins might account for the increased risk of cancer among those consuming fermented pancakes, we obtained specimens of corn, cornmeal, unfermented and fermented pancake batter, and cooked fermented pancakes from each of 16 households in Linqu County for analysis by the U.S. Department of Agriculture, Fumonisins B-1, B-2, and B-3 were detected (greater than or equal to 0.5 mu g/g) in 19, 25, and 6% of the corn specimens, respectively, as well as in various corn products, No type A trichothecenes were detected;however, the type B trichothecenes deoxynivalenol and 15-acetyldeoxynivalenol were detected (greater than or equal to 0.5 mu g/g) in 58 and 17% of the corn specimens, respectively, and zearalenone was detected (greater than or equal to 0.5 mu/g) in 15% of the cornmeal specimens. The mycotoxins were detected only at low levels (< 10 mu g/g), which did not increase with fermentation. These findings do not support the hypothesis that mycotoxin contamination increases the risk of gastric cancer among those who consume fermented Chinese pancakes.

关键词：生物学鉴定法羧酸类/分析羧酸类/药理学中国发酵食品污染伏马菌素类镰刀菌属/代谢肝/代谢真菌毒素类/分析大鼠 Sprague-Dawley 鞘氨醇/类似物和衍生物鞘氨醇/代谢胃肿瘤/化学诱导胃肿瘤/流行病学单端孢霉烯类/分析玉米/化学玉米/微生物学动物男(雄)性大鼠

来源：评论

学校读者我要写书评

暂无评论

A high-performance liquid chromatographic method to measure sphingosine 1-phosphate and related compounds from sphingosine kinase assays and other biological samples

引用

ANALYTICAL BIOCHEMISTRY 2000年第1期281卷 36-44页

作者： Caligan, TB Peters, K Ou, J Wang, E Saba, J Merrill, AH Emory Univ Sch Med Dept Biochem Atlanta GA 30322 USA Childrens Hosp Oakland Res Inst Oakland CA 94609 USA

Sphingosine 1-phosphate is an intermediate of sphingosine catabolism as well as a potent signaling compound. Conditions were established for the extraction and analysis of sphingosine 1-phosphate and other sphingoid base 1-phosphates from in vitro sphingosine kinase assays and other biological samples. The sphingoid base 1-phosphates were extracted in high yield (85%) using small C-18 reverse-phase columns CLiChroprep RP-18). After the extracts were treated with 0.1 N KOH to remove glycerolipids, the sphingoid base 1-phosphates were converted to fluorescent o-phthalaldehyde derivatives that were separated by HPLC using C-18 columns with a mobile phase of methanol:10 mM, potassium phosphate (pH 7.2):1 M tetrabutylammonium dihydrogen phosphate tin water) (83:16:1, v/v/v). The o-phthalaldehyde derivative of sphingosine 1-phosphate was reasonably stable (t(1/2) greater than or equal to 18 h) when EDTA was present and could be detected in picomole amounts. The HPLC retention time of the sphingoid base 1-phosphates could be shifted by adjusting the mobile phase to pH 5.5, which is useful in separating overlapping compounds (such as sphingosine 1-phosphate and 4-D-hyrdroxysphinganine) and in confirming the identity of sphingoid base 1-phosphhates in biological samples. The extraction procedure and HPLC method facilitated assays of sphingosine kinase with different sphingoid bases as substrates and/or inhibitors and enabled the quantitation of sphingoid base 1-phosphates in human plasma, serum, and platelets as well as in strains of Saccharomyces cerevisae with mutations in sphingolipid metabolism. (C) 2000 Academic Press.

关键词：血小板/化学色谱法高压液相/方法溶血磷脂素类磷酸盐类/分析磷酸盐类/化学磷酸转移酶类(醇族体)/代谢酵母菌酿酒/化学光谱法荧光鞘氨醇/类似物和衍生物鞘氨醇/分析鞘氨醇/血液 o-酞醛/分析 o-酞醛/化学人类

来源：评论

学校读者我要写书评

暂无评论

Agonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae - eNOS activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第41期275卷 32363-32370页

作者： Igarashi, J Michel, T Harvard Univ Brigham & Womens Hosp Div Cardiovasc Sch Med Boston MA 02115 USA Vet Affairs Boston Healthcare Syst W Roxbury MA 02132 USA

Plasmalemmal caveolae are membrane microdomains that are specifically enriched in sphingolipids and contain a wide array of signaling proteins, including the endothelial isoform of nitric-oxide synthase (eNOS). EDG-1 is a G protein-coupled receptor for sphingosine 1-phosphate (S1P) that is expressed in endothelial cells and has been implicated in diverse vascular signal transduction pathways. We analyzed the subcellular distribution of EDG-1 in COS-7 cells transiently transfected with cDNA constructs encoding epitope-tagged EDG-1. Subcellular fractionation of cell lysates resolved by ultracentrifugation in discontinuous sucrose gradients revealed that similar to 55% of the EDG-1 protein was recovered in fractions enriched in caveolin-1, a resident protein of caveolae, Co-immunoprecipitation experiments showed that EDG-1 could be specifically precipitated by antibodies directed against caveolin-1 and vice versa. The targeting of EDG-1 to caveolae-enriched fractions was markedly increased (from 51 +/- 11% to 93 +/- 14%) by treatment of transfected cells with S1P (5 mu M, 60 min). In co-transfection experiments expressing EDG-1 and eNOS cDNAs in COS-7 cells, we found that S1P treatment significantly and specifically increased nitric-oxide synthase activity, with an EC50 of 30 nM S1P. Overexpression of transfected caveolin-1 cDNA together with EDG-1 and eNOS markedly diminished S1P-mediated eNOS activation;caveolin overexpression also attenuated agonist-induced phosphorylation of EDG-1 receptor by >90%. These results suggest that the interaction of the EDG-1 receptor with caveolin may serve to inhibit signaling through the S1P pathway, even as the targeting of EDG-1 to caveolae facilitates the interactions of this receptor with ligands and effecters that are also targeted to caveolae. The agonist-modulated targeting of EDG-1 to caveolae and its dynamic inhibitory interactions with caveolin identify new points for regulation of sphingolipid-dependent signaling in the vas

关键词：溶血磷脂素类一氧化氮/代谢一氧化氮合酶/代谢磷酰化/药物作用沉淀素试验蛋白质结合/药物作用蛋白质转运/药物作用受体细胞表面受体 G-蛋白偶联受体溶血磷脂重组融合蛋白质类/代谢信号传导/药物作用鞘氨醇/类似物和衍生物鞘氨醇/拮抗剂和抑制剂鞘氨醇/药理学转染

来源：评论

学校读者我要写书评

暂无评论

Sphingosine 1-phosphate stimulates cell migration through a G_i-coupled cell surface receptor -: Potential involvement in angiogenesis

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第50期274卷 35343-35350页

作者： Wang, F Van Brocklyn, JR Hobson, JP Movafagh, S Zukowska-Grojec, Z Milstien, S Spiegel, S Georgetown Univ Med Ctr Dept Biochem & Mol Biol Washington DC 20007 USA Georgetown Univ Med Ctr Dept Physiol & Biophys Washington DC 20007 USA NIMH Lab Cellular & Mol Regulat NIH Bethesda MD 20892 USA

Sphingosine l-phosphate (SPP) has been shown to inhibit chemotaxis of a variety of cells, in some cases through intracellular actions, while in others through receptor-mediated effects. Surprisingly, we found that low concentrations of SPP (10-100 nm) increased chemotaxis of HEK293 cells overexpressing the G protein-coupled SPP receptor EDG-1. In agreement with previous findings in human breast cancer cells (Wang, F., Nohara, K., Olivera, O., Thompson, E. W., and Spiegel, S. (1999) Exp. Cell Res. 247, 17-28), SPP, at micromolar concentrations, inhibited chemotaxis of both vector- and EDG-1-overexpressing HEK293 cells. Nanomolar concentrations of SPP also induced a marked increase in chemotaxis of human umbilical vein endothelial cells (HUVEC) and bovine aortic endothelial cells (BAEC), which express the SPP receptors EDG-1 and EDG-3, while higher concentrations of SPP were less effective. Treatment with pertussis toxin, which ADP-ribosylates and inactivates G(i)-coupled receptors, blocked SPP-induced chemotaxis. Checkerboard analysis indicated that SPP stimulates both chemotaxis and chemokinesis. Taken together, these data suggest that SPP stimulates cell migration by binding to EDG-1. Similar to SPP, sph-inganine 1-phosphate (dihydro-SPP), which also binds to this family of SPP receptors, enhanced chemotaxis;whereas, another structurally related lysophospholipid, lysophosphatidic acid, did not compete with SPP for binding nor did it have significant effects on chemotaxis of endothelial cells. Furthermore, SPP increased proliferation of HUVEC and BAEC in a pertussis toxin-sensitive manner. SPP and dihydro-SPP also stimulated tube formation of BAEC grown on collagen gels (in vitro angiogenesis), and potentiated tube formation induced by basic fibroblast growth factor. Pertussis toxin treatment blocked SPP-, but not bFGF-stimulated in vitro angiogenesis. Our results suggest that SPP may play a role in angiogenesis through binding to endothelial cell Gi-coupled SPP rec

关键词：主动脉细胞分裂/药物作用细胞系细胞培养的趋化作用/药物作用趋化作用/生理学 DNA/生物合成 DNA结合蛋白质类/遗传学 DNA结合蛋白质类/生理学剂量效应关系药物内皮血管/细胞学内皮血管/药物作用内皮血管/生理学成纤维细胞生长因子2/药理学 GTP结合蛋白质α亚单位 Gi-Go/生理学 I-κB蛋白质类即早蛋白质类/遗传学即早蛋白质类/生理学动力学溶血磷脂素类新生血管化生理性/药物作用新生血管化生理性/生理学受体细胞表面/生理学受体 G-蛋白偶联受体溶血磷脂重组蛋白质类/代谢逆转录聚合酶链反应鞘氨醇/类似物和衍生物鞘氨醇/药代动力学鞘氨醇/药理学转染脐静脉动物牛人类

来源：评论

学校读者我要写书评

暂无评论

Expression of a catalytically inactive sphingosine kinase mutant blocks agonist-induced sphingosine kinase activation - A dominant-negative sphingosine kinase

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第43期275卷 33945-33950页

作者： Pitson, SM Moretti, PAB Zebol, JR Xia, P Gamble, JR Vadas, MA D'Andrea, RJ Wattenberg, BW Univ Adelaide Inst Med & Vet Sci Div Human Immunol Hanson Ctr Canc Res Adelaide SA 5000 Australia Univ Adelaide Dept Med Adelaide SA 5000 Australia

Sphingosine kinase (SK) catalyzes the formation of sphingosine 1-phosphate (S1P), a lipid messenger that plays an important role in a variety of mammalian cell processes, including inhibition of apoptosis and stimulation of cell proliferation. Basal levels of SIP in cells are generally low but can increase rapidly when cells are exposed to various agonists through rapid and transient activation of SK activity. To date, elucidation of the exact signaling pathways affected by these elevated S1P levels has relied on the use of SK inhibitors that are known to have direct effects on other enzymes in the cell. Furthermore, these inhibitors block basal SK activity, which is thought to have a housekeeping function in the cell. To produce a specific inhibitor of SK activation we sought to generate a catalytically inactive, dominant-negative SK. This was accomplished by site-directed mutagenesis of Gly(82) to Asp of the human SK, a residue identified through sequence similarity to the putative catalytic domain of diacylglycerol kinase. This mutant had no detectable SK activity when expressed at high levels in HEK293T cells. Activation of endogenous SK activity by tumor necrosis factor-alpha (TNF alpha), interleukin-lp, and phorbol esters in HEK293T cells was blocked by expression of this inactive sphingosine kinase (hSK(G82D)), Basal SK activity was unaffected by expression of hSR(G82D). Expression of hSK(G82D) had no effect on TNF alpha -induced activation of protein kinase C and sphingomyelinase activities. Thus, hSK(G82D) acts as a specific dominant-negative SK to block SK activation. This discovery provides a powerful tool for the elucidation of the exact signaling pathways affected by elevated S1P levels following SK activation. To this end we have employed the dominant-negative SK to demonstrate that TNF alpha activation of extracellular signal-regulated kinases 1 and 2 (ERK1,2) is dependent on SK activation.

关键词：鞘氨醇/类似物和衍生物鞘氨醇/代谢肿瘤坏死因子α/药理学

来源：评论

学校读者我要写书评

暂无评论

Nitric oxide inhibits the tumor necrosis factor α-regulated endocytosis of human dendritic cells in a cyclic GMP-dependent way

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第26期275卷 19638-19644页

作者： Paolucci, C Rovere, P De Nadai, C Manfredi, AA Clementi, E Ist Sci San Raffaele DIBIT Dept Neurosci I-20132 Milan Italy Ist Sci San Raffaele Lab Tumour Immunol Gene Therapy Programme I-20132 Milan Italy CNR Ctr Cellular & Mol Pharmacol I-20129 Milan Italy Univ Calabria Dept Pharmacobiol I-87036 Arcavacata Di Rende Italy

Tumor necrosis factor-alpha (TNF alpha)-induced maturation of dendritic cells (DC), with down-regulation of their endocytic ability, has been reported to be mediated by the accumulation of the lipid messenger ceramide. We have now studied the effects and mechanisms of action of NO on endocytosis, investigated with fluorescein isothiocyanate-labeled dextran using human monocyte-derived DC, both immature and after treatment with TNF alpha. Exposure of DC to NO, released by either bystander phagocytes or NO donors, reversed the inhibition of endocytosis induced by TNF alpha. The intracellular accumulation of ceramide induced by TNF alpha was also inhibited by NO. In addition, NO was found to exert an inhibitory effect downstream of the TNF alpha-triggered ceramide accumulation, because NO donors reversed the inhibition of endocytosis induced by the cell-permeant C-2-ceramide. These effects of NO were mimicked by the membrane-permeant cyclic GMP analogue, 8-Br cyclic GMP, and prevented by inhibition of the soluble guanylyl cyclase. At variance with rodents, the inducible isoform of the NO synthase was expressed neither in immature human DC nor after cell treatment with TNF alpha, interferon-gamma, and lipopolysaccharide, suggesting that regulation of these cells depends on exogenous NO, NO, working through cyclic GMP, might therefore prolong the ability of human DC to internalize antigens at the site of inflammation and thus modulate the initial steps leading to antigen-specific immune responses.

关键词：印迹法蛋白质脑/代谢细胞培养的神经酰胺类/药代动力学共同培养技术环GMP/代谢树突细胞/代谢减量调节胞吞作用/生理学酶抑制剂/药代动力学流式细胞术粒细胞巨噬细胞集落刺激因子/药理学白细胞介素4/药理学白细胞单核/代谢脂多糖类/代谢一氧化氮/药理学一氧化氮合酶/代谢一氧化氮合酶Ⅱ型鞘氨醇/类似物和衍生物鞘氨醇/药代动力学时间因素肿瘤坏死因子α/拮抗剂和抑制剂肿瘤坏死因子α/代谢动物人类小鼠

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：