共查询到17条相似文献,搜索用时 0 毫秒
1.
Schaefer U Schneider A Rudroff C Neugebauer E 《Cellular and molecular life sciences : CMLS》2003,60(9):1968-1981
During agonist-dependent long-term stimulation of cells, histamine receptor subtypes are frequently down-regulated. However, the mechanisms underlying the modulation of receptor expression during long-term histamine stimulation have yet to be resolved. Based on our recently reported results showing an H1-mediated down-regulation of histamine H2 receptor mRNA in endothelial cells, our aim was to characterize the mechanism controlling rapid and long-term histamine-mediated modulation of H2 receptor expression in more detail. We were able to show that the histamine-induced down-regulation of H2 receptor mRNA and cell surface expression lasting for 24 h was accompanied by augmentation of the receptor protein level in the cytoplasmatic fraction of endothelial cells for this time period. Furthermore, changes in receptor protein levels in whole-cell lysate were negligible, indicating that the rapid and prolonged modulation of cell surface H2 receptor levels by histamine was regulated solely via internalization. The role of nitric oxide (NO) as a key mediator in histamine-stimulated cell responses was underlined by subsequent studies showing the attenuation of histamine-induced H2 receptor mRNA down-regulation and protein trafficking following NO synthase isozyme inhibition.Received 11 March 2003; received after revision 11 June 2003; accepted 17 June 2003 相似文献
2.
Glass R Loesch A Bodin P Burnstock G 《Cellular and molecular life sciences : CMLS》2002,59(5):870-881
We investigated the expression of P2X4 and P2X6 receptors on human umbilical vein endothelial cells (HUVECs) and found that both P2X receptor subtypes on plasma membranes
are largely restricted to areas of cell-cell contact. Co-labelling experiments at the confocal and electron microscopy levels
revealed that P2X4 and P2X6 receptors are strongly co-localised with the cell adhesion molecule VE-cadherin. The P2X4 and P2X6 receptors on plasma membranes at cellular junctions are rapidly (within 5 min) internalised specifically after decreasing
extracellular [Ca2+]. Disruption of microfilaments, microtubules and integrin-mediated adhesion or stimulation of P2 receptors with ATP did not
alter P2X4 and P2X6 receptor expression on HUVEC plasma membranes. Membraneous P2X4 and P2X6 receptors resisted extraction with Triton-X 100, whereas cytoplasmic P2X receptors were Triton-X 100 soluble. P2X4 receptors, but not P2X6 receptors, could be co-immunoprecipitated with VE-cadherin and vice versa. We conclude that P2X4 and P2X6 receptors are associated with VE-cadherin at HUVEC adherens junctions.
Received 15 March 2002; revised 15 March 2002; accepted 19 March 2002 相似文献
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Savaskan NE Rocha L Kotter MR Baer A Lubec G van Meeteren LA Kishi Y Aoki J Moolenaar WH Nitsch R Bräuer AU 《Cellular and molecular life sciences : CMLS》2007,64(2):230-243
Autotaxin is a secreted cell motility-stimulating exo-phosphodiesterase with lysophospholipase D activity that generates bioactive
lysophosphatidic acid. Lysophosphatidic acid has been implicated in various neural cell functions such as neurite remodeling,
demyelination, survival and inhibition of axon growth. Here, we report on the in vivo expression of autotaxin in the brain during development and following neurotrauma. We found that autotaxin is expressed in
the proliferating subventricular and choroid plexus epithelium during embryonic development. After birth, autotaxin is mainly
found in white matter areas in the central nervous system. In the adult brain, autotaxin is solely expressed in leptomeningeal
cells and oligodendrocyte precursor cells. Following neurotrauma, autotaxin is strongly up-regulated in reactive astrocytes
adjacent to the lesion. The present study revealed the cellular distribution of autotaxin in the developing and lesioned brain
and implies a function of autotaxin in oligodendrocyte precursor cells and brain injuries.
Received 18 September 2006; received after revision 30 October 2006; accepted 4 December 2006 相似文献
5.
Dhar-Chowdhury P Malester B Rajacic P Coetzee WA 《Cellular and molecular life sciences : CMLS》2007,64(23):3069-3083
Glycolysis is an evolutionary conserved metabolic pathway that provides small amounts of energy in the form of ATP when compared
to other pathways such as oxidative phosphorylation or fatty acid oxidation. The ATP levels inside metabolically active cells
are not constant and the local ATP level will depend on the site of production as well as the respective rates of ATP production,
diffusion and consumption. Membrane ion transporters (pumps, exchangers and channels) are located at sites distal to the major
sources of ATP formation (the mitochondria). We review evidence that the glycolytic complex is associated with membranes;
both at the plasmalemma and with membranes of the endo/sarcoplasmic reticular network. We examine the evidence for the concept
that many of the ion transporters are regulated preferentially by the glycolytic process. These include the Na+/K+-ATPase, the H+-ATPase, various types of Ca2+-ATPases, the Na+/H+ exchanger, the ATP-sensitive K+ channel, cation channels, Na+ channels, Ca2+ channels and other channels involved in intracellular Ca2+ homeostasis. Regulation of these pumps, exchangers and ion channels by the glycolytic process has important consequences
in a variety of physiological and pathophysiological processes, and a better understanding of this mode of regulation may
have important consequences for developing future strategies in combating disease and developing novel therapeutic approaches.
Received 20 July 2007; received after revision 30 July 2007; accepted 17 August 2007 相似文献
6.
Liver X receptors in cardiovascular and metabolic disease 总被引:5,自引:0,他引:5
Liver X receptors (LXRs) α and β are nuclear oxysterol receptors and metabolic sensors initially found to regulate cholesterol
metabolism and lipid biosynthesis. Recent studies have elucidated the importance of LXR in the development of cardiovascular
diseases and metabolic disorders. LXR agonists prevent development of atherosclerosis by modulation of metabolic as well as
inflammatory gene expression in rodent models. Moreover, LXR activation inhibits hepatic gluconeogenesis and lowers serum
glucose levels, indicating possible application of LXR activation in the treatment of diabetes mellitus. However, first-generation
LXR agonists elevate hepatic and serum trigylceride levels, making subtype-specific agonists and selective LXR modulators
rather than unselective LXR agonists a potential pharmacological strategy. This review summarizes the multiple physiological
and pathophysiological implications of LXRs and observations that identify LXRs as potential targets for therapeutic interventions
in human cardiovascular and metabolic disease.
Received 30 August 2005; received after revision 10 October 2005; accepted 4 November 2005 相似文献
7.
Ciruela F Ferré S Casadó V Cortés A Cunha RA Lluis C Franco R 《Cellular and molecular life sciences : CMLS》2006,63(21):2427-2431
Since 1990 it has been known that dimers are the basic functional form of nearly all G-protein-coupled receptors (GPCRs) and
that homo- and heterodimerization may play a key role in correct receptor maturation and trafficking to the plasma membrane.
Nevertheless, homo- and heterodimerization of GPCR has become a matter of debate especially in the search for the precise
physiological meaning of this phenomenon. This article focuses on how heterodimerization of adenosine A1 and A2A receptors, which are coupled to apparently opposite signalling pathways, allows adenosine to exert a fine-tuning modulation
of striatal glutamatergic neurotransmission, providing a switch mechanism by which low and high concentrations of adenosine
inhibit and stimulate, respectively, glutamate release.
Received 8 May 2006; received after revision 19 June 2006; accepted 17 July 2006 相似文献
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H. Matsuoka K. Yamada K. Atarashi M. Takagi T. Sugimoto 《Cellular and molecular life sciences : CMLS》1990,46(7):726-728
Summary To investigate the roles of adenosine A1 and A2 receptors in the regulation of aldosterone production, we examined the effects of adenosine and adenosine agonists (N6-cyclohexyl adenosine; selective adenosine A1 receptor agonist and 5-N-ethylcarboxamine adenosine; selective adenosine A2 receptor agonist) on aldosterone and cyclic AMP production in rat adrenal capsular cells. Neither adenosine nor 5-N-ethylcarboxamine adenosine caused significant effects on basal aldosterone or cyclic AMP production. Also, adenosine (10–3M) showed no consistent effects on aldosterone and cyclic AMP production induced by ACTH. On the other hand, N6-cyclohexyl adenosine exhibited a significant inhibition of basal aldosterone and cyclic AMP production at doses of 10–4 M and 10–3 M; furthermore, 10–3 M N6-cyclohexyl adenosine inhibited aldosterone and cyclic AMP production stimulated by ACTH. These results suggest that adenosine A1 receptors are coupled to and inhibit adenylate cyclase and may be involved in the inhibition of aldosterone production. 相似文献
10.
Bitter peptides and bitter taste receptors 总被引:1,自引:0,他引:1
Bitter peptides are a structurally diverse group of oligopeptides often generated in fermented, aged, and hydrolyzed food
products that make them unfavorable for consumption. Humans perceive bitterness by a repertoire of 25 human bitter receptors,
termed T2Rs. Knowledge of the structural features of bitter receptors and of the factors that stimulate bitter receptors will
aid in understanding the mechanism responsible for bitter taste perception. This article reviews the current knowledge regarding
structural features of bitter peptides and bitter taste receptors.
Received 24 November 2008; received after revision 11 December 2008; accepted 16 December 2008 相似文献
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12.
Enzymes and receptors in the leukotriene cascade 总被引:7,自引:0,他引:7
Leukotrienes are a family of paracrine hormones derived from the oxidative metabolism of arachidonic acid. These lipid mediators
are recognized as important signal molecules in a variety of inflammatory and allergic conditions affecting the skin, joints,
gastrointestinal and respiratory systems, in particular asthma. Such conditions are typified by local pain, tissue edema,
hyperemia and functional losses. In the tissues, immunocompetent cells accumulate at the site of injury which contribute to
tissue damage and perpetuation of the disease process. Leukotrienes can elicit most, if not all, of these signs and symptoms.
Thus, leukotriene B4 is one of the most powerful chemotactic agents known to date and participates in the recruitment of leukocytes. The cysteinyl
leukotrienes, on the other hand, contract smooth muscles, particularly in the peripheral airways and microcirculation. Recently,
drugs which block the formation and action of leukotrienes have been introduced as novel antiasthmatic medications. This chapter
reviews the biochemistry, molecular biology and cell biology of the key enzymes and cognate receptors in the leukotriene cascade. 相似文献
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Studies have shown prostaglandin F2α
to be an endogenous tumor promoter in mouse models of skin carcinogenesis; however, the mechanisms by which PGF2α affects cell cycle events remain unknown. Here we performed cell cycle analyses on HEK cells stably expressing the human
FP receptor and found that treatment with PGF2α delays mitosis and is associated with an increased expression of cyclin B1 and Cdc2 kinase activity. In addition, multipolar
spindles and misaligned chromosomes were observed in a significant proportion of cells treated with PGF2α. Defective cytokinesis was also observed which resulted in gross aneuploidy and polyploidy. Expression of dominant negative
Rho attenuated the cell cycle delay and prevented the generation of micronuclei following treatment with PGF2α. This suggests that FP receptor activation of Rho signaling by PGF2α can interfere with nuclear division. Aneuploidy is associated with genomic instability and may underlie the tumor-promoting
properties of PGF2α.
Received 7 July 2005; received after revision 22 October 2005; accepted 11 November 2005 相似文献
15.
Many notions regarding the function, structure and regulation of cholera toxin expression have remained essentially unaltered
in the last 15 years. At the same time, recent findings have generated additional perspectives. For example, the cholera toxin
genes are now known to be carried by a non-lytic bacteriophage, a previously unsuspected condition. Understanding of how the
expression of cholera toxin genes is controlled by the bacterium at the molecular level has advanced significantly and relationships
with cell-density-associated (quorum-sensing) responses have recently been discovered. Regarding the cell intoxication process,
the mode of entry and intracellular transport of cholera toxin are becoming clearer. In the immunological field, the strong
oral immunogenicity of the non-toxic B subunit of cholera toxin (CTB) has been exploited in the development of a now widely
licensed oral cholera vaccine. Additionally, CTB has been shown to induce tolerance against co-administered (linked) foreign
antigens in some autoimmune and allergic diseases.
Received 25 October 2007; accepted 12 December 2007 相似文献
16.
P. Protais D. Cortes J. -L. Pons S. Lopez M. C. Villaverde L. Castedo 《Cellular and molecular life sciences : CMLS》1992,48(1):27-30
Five natural cularines isolated from the aerial parts ofSarcocapnos crassifolia (Fumariaceae) and a cularioid isolated from the bark ofGuatteria ouregou (Annonaceae) were tested for their ability to displace3H-SCH 23 390 and3H-raclopride from their striatal binding sites. Celtisine, breoganine and cularidine were able to inhibit the binding at D-1 and D-2 dopaminergic sites at nanomolar concentrations. Other alkaloids were active at micromolar concentrations. These data suggest that the presence of an oxepine system in the isoquinoline skeleton could lead to compounds which would be very active and possibly selective at dopaminergic receptor sites. 相似文献
17.
S. P. Yun M. Y. Lee J. M. Ryu H. J. Han 《Cellular and molecular life sciences : CMLS》2009,66(9):1603-1616
Identifying the small molecules that permit precise regulation of embryonic stem (ES) cell proliferation should further support
our understanding of the underlying molecular mechanisms of self renewal. In the present study, we showed that PGE2 increased [3H]-thymidine incorporation in a time and dose dependent manner. In addition, PGE2 increased the expression of cell cycle regulatory proteins, the percentage of cells in S phase and the total number of cells.
PGE2 obviously increased E-type prostaglandin (EP) receptor 1 mRNA expression level compare to 2, 3, 4 subtypes. EP1 antagonist
also blocked PGE2-induced cell cycle regulatory protein expression and thymidine incorporation. PGE2 caused phosphorylation of protine kinase C, Src, epidermal growth factor (EGF) receptor, phosphatidylinositol 3-kinase (PI3K)/Akt
phosphorylation, and p44/42 mitogen-activated protein kinase (MAPK), which were blocked by each inhibitors. In conclusion,
PGE2-stimulated proliferation is mediated by MAPK via EP1 receptor-dependent PKC and EGF receptor-dependent PI3K/Akt signaling
pathways in mouse ES cells.
Received 30 January 2009; received after revision 03 March 2009; accepted 10 March 2009 相似文献