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991.
992.
993.
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
994.
Increase in neuronal nitric oxide synthase content of the gastroduodenal tract of diabetic rats 总被引:3,自引:0,他引:3
Adeghate E al-Ramadi B Saleh AM Vijayarasathy C Ponery AS Arafat K Howarth FC El-Sharkawy T 《Cellular and molecular life sciences : CMLS》2003,60(6):1172-1179
This study examined the changes occurring in the pattern of distribution and expression of neuronal nitric oxide synthase (nNOS)-positive nerves in the gastroduodenal tract of streptozotocin-induced diabetic rats. The ganglion cells of the myenteric plexus of the gastric antrum of normal rats contain nNOS. We also observed nNOS-positive neurons and fibres in the myenteric plexus of the duodenum of normal rats. After the onset of diabetes, the number and intensity of staining of nNOS-positive nerve profiles in the gastric antrum and duodenum did not change significantly. However, Western blotting showed a significant increase in the expression of nNOS after the onset of diabetes. In conclusion, diabetes of 4 and 32 weeks duration induced an increase in the tissue content of nNOS in the gastroduodenum of rat. The increase in the level of nNOS in the gastroduodenum of diabetic rats may explain why impaired gastric emptying is common in patients with diabetes. 相似文献
995.
Hermann H De Petrocellis L Bisogno T Schiano Moriello A Lutz B Di Marzo V 《Cellular and molecular life sciences : CMLS》2003,60(3):607-616
Cannabinoid CB1 receptors and vanilloid VR1 receptors are co-localized to some extent in sensory neurons of the spinal cord and dorsal root ganglia. In this study, we over-expressed both receptor types in human embryonic kidney (HEK)-293 cells and investigated the effect of the CB1 agonist HU-210 on the VR1-mediated increase in intracellular Ca2+ ([Ca2+]i), a well-known response of the prototypical VR1 agonist capsaicin. After a 5-min pre-treatment, HU-210 (0.1 microM) significantly enhanced the effect of several concentrations of capsaicin on [Ca2+]i in HEK-293 cells over-expressing both rat CB1 and human VR1 (CB1-VR1-HEK cells), but not in cells over-expressing only human VR1 (VR1-HEK cells). This effect was blocked by the CB1 receptor antagonist SR141716A (0.5 microM), and by phosphoinositide-3-kinase and phospholipase C inhibitors. The endogenous agonist of CB1 and VR1 receptors, anandamide, was more efficacious in inducing a VR1-mediated stimulation of [Ca2+]i in CB1-VR1-HEK cells than in VR1-HEK cells, and part of its effect on the former cells was blocked by SR141716A (0.5 microM). Pre-treatment of CB1-VR1-HEK cells with forskolin, an adenylate cyclase activator, enhanced the capsaicin effect on [Ca2+]i. HU-210, which in the same cells inhibits forskolin-induced enhancement of cAMP levels, blocked the stimulatory effect of forskolin on capsaicin. Our data suggest that in cells co-expressing both CB1 and VR1 receptors, pre-treatment with CB1 agonists inhibits or stimulates VR1 gating by capsaicin depending on whether or not cAMP-mediated signalling has been concomitantly activated. 相似文献
996.
Diekman AB 《Cellular and molecular life sciences : CMLS》2003,60(2):298-308
Glycoconjugates in the mammalian reproductive tract are critical components of the molecular mechanisms that control sperm
maturation, sperm transport and gamete interactions. In the oviduct of many species, sperm transport and maturation are regulated
by protein-carbohydrate interactions that form a sperm reservoir. Subsequently, gamete interactions are mediated by the binding
of lectin-like sperm proteins with carbohydrate moieties on the zona pellucida. The sperm glycocalyx is extensively modified
during sperm transport and maturation. Multiple functions have been proposed for this dense carbohydrate layer overlying the
sperm plasmalemma, and sperm-surface carbohydrates have been implicated in immune-mediated human infertility. The structure
and function of glycoconjugates in the oviductal sperm reservoir, the zona pellucida, and on the sperm surface are reviewed. 相似文献
997.
Human mitochondrial tRNAs in health and disease 总被引:6,自引:0,他引:6
Florentz C Sohm B Tryoen-Tóth P Pütz J Sissler M 《Cellular and molecular life sciences : CMLS》2003,60(7):1356-1375
The human mitochondrial genome encodes 13 proteins, all subunits of the respiratory chain
complexes and thus involved in energy metabolism. These genes are translated by 22 transfer RNAs
(tRNAs), also encoded by the mitochondrial genome, which form the minimal set required for reading
all codons. Human mitochondrial tRNAs gained interest with the rapid discovery of correlations
between point mutations in their genes and various neuromuscular and neurodegenerative disorders.
In this review, emerging fundamental knowledge on the structure/function relationships of these
particular tRNAs and an overview of the large variety of mechanisms within translation, affected by
mutations, are summarized. Also, initial results on wide-ranging molecular consequences of mutations
outside the frame of mitochondrial translation are highlighted. While knowledge of mitochondrial
tRNAs in both health and disease increases, deciphering the intricate network of events leading
different genotypes to the variety of phenotypes requires further investigation using adapted
model systems.Received 3 December 2002; received after revision 14 January 2003; accepted 27 January 2003 相似文献
998.
Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis 总被引:24,自引:0,他引:24
The pattern of blood flow in the developing heart has long been proposed to play a significant role in cardiac morphogenesis. In response to flow-induced forces, cultured cardiac endothelial cells rearrange their cytoskeletal structure and change their gene expression profiles. To link such in vitro data to the intact heart, we performed quantitative in vivo analyses of intracardiac flow forces in zebrafish embryos. Using in vivo imaging, here we show the presence of high-shear, vortical flow at two key stages in the developing heart, and predict flow-induced forces much greater than might have been expected for micro-scale structures at low Reynolds numbers. To test the relevance of these shear forces in vivo, flow was occluded at either the cardiac inflow or outflow tracts, resulting in hearts with an abnormal third chamber, diminished looping and impaired valve formation. The similarity of these defects to those observed in some congenital heart diseases argues for the importance of intracardiac haemodynamics as a key epigenetic factor in embryonic cardiogenesis. 相似文献
999.
1000.
Rawat UB Zavialov AV Sengupta J Valle M Grassucci RA Linde J Vestergaard B Ehrenberg M Frank J 《Nature》2003,421(6918):87-90
Protein synthesis takes place on the ribosome, where genetic information carried by messenger RNA is translated into a sequence of amino acids. This process is terminated when a stop codon moves into the ribosomal decoding centre (DC) and is recognized by a class-1 release factor (RF). RFs have a conserved GGQ amino-acid motif, which is crucial for peptide release and is believed to interact directly with the peptidyl-transferase centre (PTC) of the 50S ribosomal subunit. Another conserved motif of RFs (SPF in RF2) has been proposed to interact directly with stop codons in the DC of the 30S subunit. The distance between the DC and PTC is approximately 73 A. However, in the X-ray structure of RF2, SPF and GGQ are only 23 A apart, indicating that they cannot be at DC and PTC simultaneously. Here we show that RF2 is in an open conformation when bound to the ribosome, allowing GGQ to reach the PTC while still allowing SPF-stop-codon interaction. The results indicate new interpretations of accuracy in termination, and have implications for how the presence of a stop codon in the DC is signalled to PTC. 相似文献