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91.
Cell migration is central to many biological and pathological processes, including embryogenesis, tissue repair and regeneration as well as cancer and the inflammatory response. In general, cell migration can be usefully conceptualized as a cyclic process. The initial response of a cell to a migration-promoting agent is to polarize and extend protrusions in the direction of migration. These protrusions can be large, broad lamellipodia or spike-like filopodia, are usually driven by actin polymerization, and are stabilized by adhering to the extracellular matrix (ECM) via transmembrane receptors of the integrin family linked to the actin cytoskeleton. These adhesions serve as traction sites for migration as the cell moves forward over them, and they must be disassembled at the cell rear, allowing it to detach. The mechanisms of rear detachment and the regulatory processes involved are not well understood. The disassembly of adhesions that is required for detachment depends on a coordinated interaction of actin and actin-binding proteins, signaling molecules and effector enzymes including proteases, kinases and phosphatases. Originally, the biochemically regulated processes leading to rear detachment of migrating cells were thought not to be necessarily accompanied by any loss of cell material. However, it has been shown that during rear detachment long tubular extensions, the retracting fibers, are formed and that "membrane ripping" occurs at the cell rear. By this process, a major fraction of integrin-containing cellular material is left behind forming characteristic migration tracks that exactly mark the way a cell has taken. 相似文献
92.
Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to this molecule. After its discovery in the early 1970, thymulin was characterized as a thymic hormone involved in several aspects of intra- and extrathymic T-cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, an emerging core of information points to thymulin as a hypophysotropic peptide. Here we review the evidence supporting the hypothesis that thymulin is an important player in the hypophyso-thymic axis. 相似文献
93.
Soulage C Perrin D Cottet-Emard JM Pequignot J Dalmaz Y Pequignot JM 《Neurochemistry international》2004,45(7):979-986
We investigated in rat the effects of ozone exposure (0.7 ppm) for 5 h on the catecholamine biosynthesis and turnover in sympathetic efferents and various brain areas. For this purpose, the activity of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, was assessed in superior cervical ganglia and in two major noradrenergic cell groups, A2 and A6 (locus coeruleus). Tyrosine hydroxylase activity was estimated in vivo by measuring the accumulation of l-dihydroxyphenylalanine after pharmacological blockade of L-aromatic acid decarboxylases by NSD-1015 (100 mg/kg i.p.). The catecholamine turnover rate was measured after inhibition of tyrosine hydroxylase by alpha-methyl-para-tyrosine (AMPT, 250 mg/kg, i.p., 2.5 h) in peripheral sympathetic target organ (heart and lungs) as well as in some brain catecholamine terminal areas (cerebral cortex, hypothalamus and striatum). Ozone caused differential effects according to the structure. Catecholamine biosynthesis was stimulated in superior cervical ganglia (+44%, P < 0.05) and caudal A2 subset (+126%, P < 0.01), whereas catecholamine turnover was increased in heart (+183%, P < 0.01) and cortex (+22%, P < 0.05). On the other hand, catecholamine turnover was inhibited in lungs (-53%, P < 0.05) and striatum (-24%, P < 0.05). A brief exposure to ozone, at a concentration chosen to mimic pollution level encountered in urban areas, can modulate catecholamine biosynthesis and utilization rate in the sympathetic and central neurones. 相似文献
94.
The expression of the long form of prolactin receptor (PRL-R) mRNAs was studied in reproductive organs from both male and female Typhlonectes compressicauda, an amphibian, by quantitative in situ hybridization. These PRL-R mRNAs were expressed in all the organs studied. In ovarian tissue, mRNAs coding for the long form of PRL-R were strongly expressed in ovaries with compact and vascularized corpora lutea, i.e., during the middle and the end of pregnancy. During the other periods of cycle, sexual rest, vitellogenesis and beginning of pregnancy, expression of these mRNAs was lower than in other periods. In the testis, mRNAs coding for the long form of PRL-R were expressed in germ cells as well as in Leydig and Sertoli cells. In müllerian glands, important variations of expression in these mRNAs have been observed with a large increase during the breeding period and a decrease during sexual rest. Variations of gene expression of the long form of PRL-R for all tissues studied are correlated to synthesis of PRL in the pituitary in both male and female Typhlonectes compressicauda. 相似文献
95.
Transposases are responsible for the target specificity of IS1397 and ISKpn1 for two different types of palindromic units (PUs) 总被引:1,自引:0,他引:1 下载免费PDF全文
Wilde C Escartin F Kokeguchi S Latour-Lambert P Lectard A Clément JM 《Nucleic acids research》2003,31(15):4345-4353
Insertion sequences (IS)1397 and ISKpn1, found in Escherichia coli and Klebsiella pneumoniae, respectively, are IS3 family members that insert specifically into short palindromic repeated sequences (palindromic units or PUs). In this paper, we first show that although PUs are naturally absent from extrachromosomal elements, both ISs are able to transpose from the chromosome or from a plasmid into PUs artificially introduced into target plasmids. We also show that ISKpn1 target specificity is restricted to K.pneumoniae Z1 PU type, whereas IS1397 target specificity is less stringent since the IS targets the three E.coli Y, Z1 and Z2 PU types indifferently. Experiments of transposition of both ISs driven by both transposases demonstrate that the inverted repeats flanking the ISs are not responsible for this target specificity, which is entirely due to the transposase itself. Implications on ISs evolution are presented. 相似文献
96.
Differential modulation of the human liver conjugate transporters MRP2 and MRP3 by bile acids and organic anions 总被引:9,自引:0,他引:9
Bodo A Bakos E Szeri F Varadi A Sarkadi B 《The Journal of biological chemistry》2003,278(26):23529-23537
The multidrug resistance proteins MRP2 (ABCC2) and MRP3 (ABCC3) are key primary active transporters involved in anionic conjugate and drug extrusion from the human liver. The major physiological role of MRP2 is to transport conjugated metabolites into the bile canaliculus, whereas MRP3 is localized in the basolateral membrane of the hepatocytes and transports similar metabolites back to the bloodstream. Both proteins were shown to interact with a large variety of transported substrates, and earlier studies suggested that MRPs may work as co-transporters for different molecules. In the present study we expressed the human MRP2 and MRP3 proteins in insect cells and examined their transport and ATPase characteristics in isolated, inside-out membrane vesicles. We found that the primary active transport of estradiol-17-beta-d-glucuronide (E217betaG), a major product of human steroid metabolism, was differently modulated by bile acids and organic anions in the case of human MRP2 and MRP3. Active E217betaG transport by MRP2 was significantly stimulated by the organic anions indomethacin, furosemide, and probenecid and by several conjugated bile acids. In contrast, all of these agents inhibited E217betaG transport by MRP3. We found that in the case of MRP2, ATP-dependent vesicular bile acid transport was increased by E217betaG, and the results indicated an allosteric cross-stimulation, probably a co-transport of bile acids and glucuronate conjugates through this protein. There was no such stimulation of bile acid transport by MRP3. In conclusion, the different transport modulation of MRPs by bile acids and anionic drugs could play a major role in regulating physiological and pathological metabolite fluxes in the human liver. 相似文献
97.
Johansson K Bourhis JM Campanacci V Cambillau C Canard B Longhi S 《The Journal of biological chemistry》2003,278(45):44567-44573
Measles virus is a negative-sense, single-stranded RNA virus belonging to the Mononegavirales order which comprises several human pathogens such as Ebola, Nipah, and Hendra viruses. The phosphoprotein of measles virus is a modular protein consisting of an intrinsically disordered N-terminal domain (Karlin, D., Longhi, S., Receveur, V., and Canard, B. (2002) Virology 296, 251-262) and of a C-terminal moiety (PCT) composed of alternating disordered and globular regions. We report the crystal structure of the extreme C-terminal domain (XD) of measles virus phosphoprotein (aa 459-507) at 1.8 A resolution. We have previously reported that the C-terminal domain of measles virus nucleoprotein, NTAIL, is intrinsically unstructured and undergoes induced folding in the presence of PCT (Longhi, S., Receveur-Brechot, V., Karlin, D., Johansson, K., Darbon, H., Bhella, D., Yeo, R., Finet, S., and Canard, B. (2003) J. Biol. Chem. 278, 18638-18648). Using far-UV circular dichroism, we show that within PCT, XD is the region responsible for the induced folding of NTAIL. The crystal structure of XD consists of three helices, arranged in an anti-parallel triple-helix bundle. The surface of XD formed between helices alpha2 and alpha3 displays a long hydrophobic cleft that might provide a complementary hydrophobic surface to embed and promote folding of the predicted alpha-helix of NTAIL. We present a tentative model of the interaction between XD and NTAIL. These results, beyond presenting the first measles virus protein structure, shed light both on the function of the phosphoprotein at the molecular level and on the process of induced folding. 相似文献
98.
Fernandez-Capetillo O Liebe B Scherthan H Nussenzweig A 《The Journal of cell biology》2003,163(1):15-20
The histone H2A variant H2AX is phosphorylated in response to DNA double-strand breaks originating from diverse origins, including dysfunctional telomeres. Here, we show that normal mitotic telomere maintenance does not require H2AX. Moreover, H2AX is dispensable for the chromosome fusions arising from either critically shortened or deprotected telomeres. However, H2AX has an essential role in controlling the proper topological distribution of telomeres during meiotic prophase I. Our results suggest that H2AX is a downstream effector of the ataxia telangiectasia-mutated kinase in controlling telomere movement during meiosis. 相似文献
99.
Bornet C Chollet R Malléa M Chevalier J Davin-Regli A Pagès JM Bollet C 《Biochemical and biophysical research communications》2003,301(4):985-990
Imipenem is often used to treat intensive care unit patients infected by Enterobacter aerogenes, but it is leading to an increasing number of antibiotic resistant strains. Clinical isolates and imipenem resistant variants presented a high level of resistance to beta-lactam antibiotic group and to chemically unrelated drugs. We report here that imipenem selects strains which contain active efflux pumps ejecting various unrelated antibiotics including quinolones, tetracycline, and chloramphenicol. An increase of AcrA, an efflux pump component, was observed in the imipenem resistant variants. The overexpression of marA, involved in the genetic control of membrane permeability via porin and efflux pump expression, indicated the activation of the resistance genetic cascade in imipenem resistant variants. 相似文献
100.
Dairou J Atmane N Dupret JM Rodrigues-Lima F 《Biochemical and biophysical research communications》2003,307(4):1059-1065
Human arylamine N-acetyltransferase 1 (NAT1) is a polymorphic phase II xenobiotic-metabolizing enzyme which catalyzes the biotransformation of primary aromatic amines, hydrazine drugs, and carcinogens. Structural and functional studies have shown that the NAT1 and factor XIII transglutaminase catalytic pockets are structurally related with the existence of a conserved catalytic triad (Cys-His-Asp). In addition, it has been reported that factor XIII transglutaminase activity could be regulated by nitric oxide (NO), in particular S-nitrosothiols (RSNO). We thus tested whether NAT1 could be a target of S-nitrosothiols. We show here that human NAT1 is reversibly inactivated by S-nitrosothiols such as SNAP (S-nitroso-N-acetyl-DL-penicillamine). A second-order rate constant for the inactivation of NAT1 by SNAP was determined (k(inact)=270M(-1)min(-1)) and shown to be in the same range of values reported for other enzymes. The inhibition of NAT1 by S-nitrosothiols was reversed by dithiothreitol and reduced glutathione, but not by ascorbate. As reported for some reactive cysteine-containing enzymes, our results suggest that inactivation of NAT1 by S-nitrosothiols is due to direct attack of the highly reactive cysteine residue in the enzyme active site on the sulfur of S-nitrosothiols to form a mixed disulfide between these NO-derived oxidants and NAT1. Finally, our findings suggest that, in addition to the polymorphic-dependent variation of NAT1 activity, NO-derived oxidants, in particular S-nitrosothiols, could also regulate NAT1 activity. 相似文献