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61.
Role of 17beta-estradiol administration on insulin sensitivity in the rat: implications for the insulin receptor 总被引:6,自引:0,他引:6
González C Alonso A Grueso NA Díaz F Esteban MM Fernández S Patterson AM 《Steroids》2002,67(13-14):993-1005
The role of 17beta-estradiol in the early steps of insulin action is only partially known, although its effect on glucose homeostasis has been reported. In this paper, we attempt to prove the influence of 17beta-estradiol on the insulin receptor of ovariectomized rats treated with different hormonal doses. Our results show that high doses of estradiol impair insulin sensitivity while low doses improve it. We think that these results are the consequence of changes at a molecular level, because high doses of estradiol produced lower expression of the insulin receptor gene, lower content of this receptor in target tissues, and lower phosphorylation of insulin receptor in these tissues. However, low doses of estradiol seem to produce just the opposite. The possible existence of consensus response elements in the insulin receptor gene promoter to estradiol could be controlling the expression of this gene, this control being dose and timing dependent. Moreover, we cannot discard a possible effect of estradiol on the activity of protein tyrosine phosphatases, and therefore, on the activity of the insulin receptor. These new findings improve knowledge about the possible risk for insulin resistance in women taking oral contraceptives or receiving hormonal replacement therapy around the menopause, but could also open the door towards the possible utilization of 17beta-estradiol in some diabetes cases. 相似文献
62.
Cutting edge: dynamic redistribution of tetraspanin CD81 at the central zone of the immune synapse in both T lymphocytes and APC 总被引:6,自引:0,他引:6
Mittelbrunn M Yáñez-Mó M Sancho D Ursa A Sánchez-Madrid F 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(12):6691-6695
The tetraspanin CD81 has been involved in T-dependent B cell-mediated immune responses. However, the behavior of CD81 during immune synapse (IS) formation has not been elucidated. We determined herein that CD81 redistributed to the contact area of T cell-B cell and T cell-dendritic cell conjugates in an Ag-dependent manner. Confocal microscopy showed that CD81 colocalized with CD3 at the central supramolecular activation complex. Videomicroscopy studies with APC or T cells transiently expressing CD81-green fluorescent protein (GFP) revealed that in both cells CD81 redistributed toward the central supramolecular activation complex. In T lymphocytes, CD81-GFP rapidly redistributed to the IS, whereas, in the APC, CD81-GFP formed a large accumulation in the contact area that later concentrated in a discrete cluster and waves of CD81 accumulated at the IS periphery. These results suggest a relevant role for CD81 in the topography of the IS that would explain its functional implication in T cell-B cell collaboration. 相似文献
63.
The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents 总被引:8,自引:0,他引:8
Lubetsky JB Dios A Han J Aljabari B Ruzsicska B Mitchell R Lolis E Al-Abed Y 《The Journal of biological chemistry》2002,277(28):24976-24982
Macrophage migration inhibitory factor (MIF) is an immunoregulatory protein that is a potential therapeutic target for a number of inflammatory diseases. Evidence exists that an unexpected catalytic active site of MIF may have a biological function. To gain further insight into the role of the catalytic active site, a series of mutational, structural, and biological activity studies were performed. The insertion of an alanine between Pro-1 and Met-2 (PAM) abolishes a non-physiological catalytic activity, and this mutant is defective in the in vitro glucocorticoid counter-regulatory activity of MIF. The crystal structure of MIF complexed to (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), an inhibitor of MIF d-dopachrome tautomerase activity, reveals that ISO-1 binds to the same position of the active site as p-hydroxyphenylpyruvic acid, a substrate of MIF. ISO-1 inhibits several MIF biological activities, further establishing a role for the catalytic active site of MIF. 相似文献
64.
65.
The role of astroglia on the survival of dopamine neurons 总被引:5,自引:0,他引:5
Mena MA de Bernardo S Casarejos MJ Canals S Rodríguez-Martín E 《Molecular neurobiology》2002,25(3):245-263
Glial cells play a key role in the function of dopamine (DA) neurons and regulate their differentiation, morphology, physiological
and pharmacological properties, survival, and resistance to different models of DA lesion. Several studies suggest that glial
cells may be important in the pathogenesis of Parkinson’s disease (PD), a common neurodegenerative disorder characterized
by degeneration of the nigrostriatal DA system. In this disease the role of glia could be due to the excessive production
of toxic products such as nitric oxide (NO) or cytokines characteristic of inflammatory process, or related to a defective
release of neuroprotective agents, such as small antioxidants with free radical scavenging properties or peptidic neurotrophic
factors. 相似文献
66.
Solinís MA de la Cruz Y Calvo B Hernández RM Gascón AR Goñi I Gurruchaga MD Pedraz JL 《Chirality》2002,14(10):806-813
We studied the release of salbutamol and ketoprofen enantiomers from HPMC K100M matrices containing two types of cellulose derivatives: cellulose tris (3,5-dimethylphenylcarbamate) and cellulose tris (2,3-dichlorophenylcarbamate), chiral excipients used as stationary phases for liquid chromatography. These matrices provided an extended release of both drugs. Ketoprofen release from formulations elaborated with cellulose tris (2,3-dichlorophenylcarbamate) was by anomalous transport, because the value of n (release exponent of the diffusion equation) ranged between 0.60-0.68, whereas for all other formulations the value of exponent n ranged from 0.50-0.54. The drug thus diffuses through the matrix and is released following a quasi-Fickian diffusion mechanism (stereoselective process). The matrices preferentially retained R-salbutamol and S-ketoprofen and cellulose tris (3,5-dimethylphenylcarbamate) showed more capacity of chiral discrimination for both drugs than cellulose tris (2,3-dichlorophenylcarbamate). Moreover, we observed that stereoselectivity is dependent on the amount of chiral excipient in the formulation. Diffusion tests confirmed the chiral interaction between drugs and cellulose derivatives observed in the dissolution assays except for matrices elaborated with ketoprofen and cellulose tris (2,3-dichlorophenylcarbamate), where the low stereoselectivity observed with the matrices is due to the presence of HPMC K100M. We conclude that the inclusion of these cellulose derivatives in HPMC matrices does not result in a relevant stereoselectivity with respect to the two drugs studied. 相似文献
67.
Olivares EC Hollis RP Chalberg TW Meuse L Kay MA Calos MP 《Nature biotechnology》2002,20(11):1124-1128
We used the integrase from phage phiC31 to integrate the human Factor IX (hFIX) gene permanently into specific sites in the mouse genome. A plasmid containing attB and an expression cassette for hFIX was delivered to the livers of mice by using high-pressure tail vein injection. When an integrase expression plasmid was co-injected, hFIX serum levels increased more than tenfold to approximately 4 microg/ml, similar to normal FIX levels, and remained stable throughout the more than eight months of the experiment. hFIX levels persisted after partial hepatectomy, suggesting genomic integration of the vector. Site-specific integration was proven by characterizing and quantifying genomic integration in the liver at the DNA level. Integration was documented at two pseudo-attP sites, native sequences with partial identity to attP, with one site highly predominant. This study demonstrates in vivo gene transfer in an animal by site-specific genomic integration. 相似文献
68.
García-Carreño FL Albuquerque-Cavalcanti C Navarrete del Toro MA Zaniboni-Filho E 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2002,132(2):343-352
Juvenile piracanjuba, Brycon orbignyanus, in the wild consume protein from both plant and animal sources. Digestion of protein in piracanjuba begins in the stomach with pepsin, at low pH, and is followed by hydrolysis at alkaline pH in the lumen of the intestine. The digestive system in piracanjuba was evaluated to characterize the enzymes responsible for the digestion of feed protein and their composition. The gastric tissue synthesizes pepsin and the intestine tissues trypsin and chymotrypsin. Operational variables were evaluated and defined for future studies of the digestive system physiology. The enzymatic activity in the intestine and the relative concentration of enzymes were heavily influenced by the composition of the feed and the feeding regime, as detected by substrate-SDS-PAGE. Piracanjuba possess a mechanism of enzyme adaptation responding to food quality and regime, by varying the amount and composition of digestive proteases. This is a requisite study to determine the enzymes digesting protein in food and their characteristics and to gain some clues about the possible regulation mechanisms of enzyme synthesis in piracanjuba. 相似文献
69.
Enzymatic acylation of di- and trisaccharides with fatty acids: choosing the appropriate enzyme,support and solvent 总被引:5,自引:0,他引:5
Plou FJ Cruces MA Ferrer M Fuentes G Pastor E Bernabé M Christensen M Comelles F Parra JL Ballesteros A 《Journal of biotechnology》2002,96(1):55-66
Enzymatic synthesis of fatty acid esters of di- and trisaccharides is limited by the fact that most biological catalysts are inactivated by the polar solvents (e.g. dimethylsulfoxide, dimethylformamide) where these carbohydrates are soluble. This article reviews the methodologies developed to overcome this limitation, namely those involving control over the reaction medium, the enzyme and the support. We have proposed the use of mixtures of miscible solvents (e.g. dimethylsulfoxide and 2-methyl-2-butanol) as a general strategy to acylate enzymatically hydrophilic substrates. We observed that decreasing the hydrophobicity of the medium (i.e. lowering the percentage of DMSO) the molar ratio sucrose diesters versus sucrose monoesters can be substantially enhanced. The different regioselectivity exhibited by several lipases and proteases makes feasible to synthesise different positional isomers, whose properties may vary considerably. In particular, the lipase from Thermomyces lanuginosus displays a notable selectivity for only one hydroxyl group in the acylation of sucrose, maltose, leucrose and maltotriose, compared with lipase from Candida antarctica. We have examined three immobilisation methods (adsorption on polypropylene, covalent coupling to Eupergit C, and silica-granulation) for sucrose acylation catalysed by T. lanuginosus lipase. The morphology of the support affected significantly the reaction rate and/or the selectivity of the process. 相似文献
70.
Inestrosa N De Ferrari GV Garrido JL Alvarez A Olivares GH Barría MI Bronfman M Chacón MA 《Neurochemistry international》2002,41(5):341-344
Alzheimer's disease (AD) is a progressive dementia paralleled by selective neuronal death, which is probably caused by the cytotoxic effects of the amyloid-beta peptide (Abeta). We have observed that Abeta-dependent neurotoxicity induces a loss of function of Wnt signaling components and that activation of this signaling cascade prevent such cytotoxic effects. Therefore we propose that compounds which mimic this signaling cascade may be candidates for therapeutic intervention in Alzheimer's patients. 相似文献