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41.
42.
Palmer G Burger D Mezin F Magne D Gabay C Dayer JM Guerne PA 《Arthritis research & therapy》2004,6(3):R181-R189
Leflunomide is an immunomodulatory agent used for the treatment of rheumatoid arthritis. In this study, we investigated the
effect of A77 1726 – the active metabolite of leflunomide – on the production of IL-1 receptor antagonist (IL-1Ra) by human
synovial fibroblasts and articular chondrocytes. Cells were incubated with A77 1726 alone or in combination with proinflammatory
cytokines. IL-1Ra production was determined by ELISA. A77 1726 alone had no effect, but in the presence of IL-1β or tumour
necrosis factor-α it markedly enhanced the secretion of IL-1Ra in synovial fibroblasts and chondrocytes. The effect of A77
1726 was greatest at 100 μmol/l. In synovial fibroblasts and de-differentiated chondrocytes, A77 1726 also increased IL-1β-induced
IL-1Ra production in cell lysates. Freshly isolated chondrocytes contained no significant amounts of intracellular IL-1Ra.
A77 1726 is a known inhibitor of pyrimidine synthesis and cyclo-oxygenase (COX)-2 activity. Addition of exogenous uridine
did not significantly modify the effect of A77 1726 on IL-1Ra production, suggesting that it was not mediated by inhibition
of pyrimidine synthesis. Indomethacin increased IL-1β-induced IL-1Ra secretion in synovial fibroblasts and de-differentiated
chondrocytes, suggesting that inhibition of COX-2 may indeed enhance IL-1β-induced IL-1Ra production. However, the stimulatory
effect of indomethacin was consistently less effective than that of A77 1726. A77 1726 increases IL-1Ra production by synovial
fibroblasts and chondrocytes in the presence of proinflammatory cytokines, and thus it may possess chondroprotective effects.
The effect of A77 1726 may be partially mediated by inhibition of COX-2, but other mechanisms likely concur to stimulate IL-1Ra
production. 相似文献
43.
Stability of the I-motif structure is related to the interactions between phosphodiester backbones
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The i-motif DNA tetrameric structure is formed of two parallel duplexes intercalated in a head-to-tail orientation, and held together by hemiprotonated cytosine pairs. The four phosphodiester backbones forming the structure define two narrow and wide grooves. The short interphosphate distances across the narrow groove induce a strong repulsion which should destabilize the tetramer. To investigate this point, molecular dynamics simulations were run on the [d(C2)]4 and [d(C4)]4 tetramers in 3'E and 5'E topologies, for which the interaction of the phosphodiester backbones through the narrow groove is different. The analysis of the simulations, using the Molecular Mechanics Generalized Born Solvation Area and Molecular Mechanics Poisson-Boltzmann Solvation Area approaches, shows that it is the van der Waals energy contribution which displays the largest relative difference between the two topologies. The comparison of the solvent-accessible area of each topology reveals that the sugar-sugar interactions account for the greater stability of the 3'E topology. This stresses the importance of the sugar-sugar contacts across the narrow groove which, enforcing the optimal backbone twisting, are essential to the base stacking and the i-motif stability. Tighter interactions between the sugars are observed in the case of N-type sugar puckers. 相似文献
44.
Martin V Bredoux R Corvazier E Van Gorp R Kovacs T Gelebart P Enouf J 《The Journal of biological chemistry》2002,277(27):24442-24452
Sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) pump Ca2+ into the endoplasmic reticulum. Recently, three human SERCA3 (h3a-c) proteins and a previously unknown rat SERCA3 (r3b/c) mRNA have been described. Here, we (i) document two novel human SERCA3 splice variants h3d and h3e, (ii) provide data for the expression and mechanisms regulating the expression of all known SERCA3 variants (r3a, r3b/c, and h3a-e), and (iii) show functional characteristics of the SERCA3 isoforms. h3d and h3e are issued from the insertion of an additional penultimate exon 22 resulting in different carboxyl termini for these variants. Distinct distribution patterns of the SERCA3 gene products were observed in a series of cell lines of hematopoietic, epithelial, embryonic origin, and several cancerous types, as well as in panels of rat and human tissues. Hypertension and protein kinase C, calcineurin, or retinoic acid receptor signaling pathways were found to differently control rat and human splice variant expression, respectively. Stable overexpression of each variant was performed in human embryonic kidney 293 cells, and the SERCA3 isoforms were fully characterized. All SERCA3 isoforms were found to pump Ca2+ with similar affinities. However, they modulated the cytosolic Ca2+ concentration ([Ca2+]c) and the endoplasmic reticulum Ca2+ content ([Ca2+]er) in different manners. A newly generated polyclonal antibody and a pan-SERCA3 antibody proved the endogenous expression of the three novel SERCA3 proteins, h3d, h3e, and r3b/c. All these data suggest that the SERCA3 gene products have a more widespread role in cellular Ca2+ signaling than previously appreciated. 相似文献
45.
Normal mating lasts approximately 3 h in Choristoneura fumiferana and C. rosaceana. Data generated from interrupted matings showed that the act of mating did not suppress pheromone production (pheromonostasis) in either species although, in C. rosaceana, pheromone titre declined slightly the night following mating. In both species the migration of sperm to the spermatheca (SP) occurred several hours after mating, and coincided with a significant and permanent depression in pheromone titre, as well as egg fertilisation and oviposition. However, disrupting matings within 2 h of the onset resulted in oviposition patterns similar to virgins in both species, with mostly infertile eggs being laid by C. fumiferana females while oviposition was totally inhibited in C. rosaceana. The transection of the ventral nerve cord (VNC) 1 h post-mating did not result in the depression of pheromone titres the following night in either species but if the VNC was transected 3 h post-mating, pheromonostasis was observed. While 25% of C. fumiferana females had sperm in their SP 2 h after mating, it took at least 4 h in C. rosaceana. This suggests that while the physical presence of sperm in the SP may play some role in the termination of pheromone production in C. fumiferana, other factors must trigger the neural signal that elicits pheromonostasis in both species. A better understanding of the temporal dynamics of both apyrene and eupyrene sperm within the different parts of the female reproductive system might clarify these interspecific differences. 相似文献
46.
Cell numbers and leaf development in Arabidopsis: a functional analysis of the STRUWWELPETER gene 总被引:1,自引:0,他引:1
Autran D Jonak C Belcram K Beemster GT Kronenberger J Grandjean O Inzé D Traas J 《The EMBO journal》2002,21(22):6036-6049
The struwwelpeter (swp) mutant in Arabidopsis shows reduced cell numbers in all aerial organs. In certain cases, this defect is partially compensated by an increase in final cell size. Although the mutation does not affect cell cycle duration in the young primordia, it does influence the window of cell proliferation, as cell number is reduced during the very early stages of primordium initiation and a precocious arrest of cell proliferation occurs. In addition, the mutation also perturbs the shoot apical meristem (SAM), which becomes gradually disorganized. SWP encodes a protein with similarities to subunits of the Mediator complex, required for RNA polymerase II recruitment at target promoters in response to specific activators. To gain further insight into its function, we overexpressed the gene under the control of a constitutive promoter. This interfered again with the moment of cell cycle arrest in the young leaf. Our results suggest that the levels of SWP, besides their role in pattern formation at the meristem, play an important role in defining the duration of cell proliferation. 相似文献
47.
Ducros V Demuth K Sauvant MP Quillard M Caussé E Candito M Read MH Drai J Garcia I Gerhardt MF;SFBC Working group on homocysteine. French Society for Clinical Biology 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,781(1-2):207-226
It is now widely accepted that increased total plasma homocysteine (tHcy) is a risk factor for cardiovascular disease. Hyperhomocysteinemia can be caused by impaired enzyme function as a result of genetic mutation or vitamin B (B(2), B(6), B(9), B(12)) deficiency. A lot of methods are now available for tHcy determination. High-pressure liquid chromatography (HPLC) with fluorescence detection are at present the most widely used methods but immunoassays, easier to use, begin to supplant in-house laboratory methods. In order to help with the choice of a main relevant homocysteine analytical method, the characteristics, performances and limits of the main current methods are reviewed. One major drawback among all these available methods is the transferability which is not clearly established to date. The impact of both inter-method and inter-laboratory variations on the interpretation of the tHcy results are discussed. 相似文献
48.
Hypoxia-inducible factor 1 transactivates the human leptin gene promoter 总被引:15,自引:0,他引:15
Grosfeld A Andre J Hauguel-De Mouzon S Berra E Pouyssegur J Guerre-Millo M 《The Journal of biological chemistry》2002,277(45):42953-42957
49.
Etchian OA Pellerin J 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2003,134(4):615-629
Aspartate transcarbamylase (ATCase, EC 2.1.3.2) has been shown to be a good index of the reproductive cycle in marine molluscs. However, this enzyme has never been studied in the soft shell clam Mya arenaria. The characteristics of gonadal ATCase of the soft shell clam, Mya arenaria were therefore determined since we need powerful tools to assess the degree of effects of endocrine disruptors in this species at risk. Enzyme kinetic values observed at pH 8.3 were significantly lower than those measured at pH 9.4. The optimal conditions for the enzyme assays were reached in the presence of a 10 mM of substrate concentration and at pH 9.2 for 60 min at 37 °C. We have found that the enzyme was heat sensitive, markedly activated by DMSO and DMF, but no effect was observed with ethanol, ATP or CTP. However, clam ATCase activity was partly inhibited by the addition of CuSO4 and PHMB to the medium, an inhibition that could be attributed to the presence of SH sites in cysteine residues localized in the catalytic site of this enzyme. All these results will be very useful in the near future to study the gametogenetic process of Mya arenaria, since little is known about the factors that control the physiological process of reproduction in this bivalve of ecological and economic importance. Studies of variations of the activity of aspartate transcarbamylase will also be useful as a potential biomarker to evaluate the disruption of gametogenesis in clams exposed to endocrine disruptors in situ. 相似文献
50.