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911.
Apostolova MD Bontchev PR Ivanova BB Russell WR Mehandjiev DR Beattie JH Nachev CK 《Journal of inorganic biochemistry》2003,95(4):321-333
During the last 2 decades it was proposed that atherogenesis was closely related to the homeostasis of homocysteine (hCys) and/or copper. We hypothesized that the physiological action of hCys may be connected with its ability to form complexes with Cu. Our results showed the presence of two different Cu-hCys complexes. At a molar ratio Cu:hCys 1:1, a blue complex most probably consistent with a tentative dimeric Cu(II)(2)(hCys)(2)(H(2)O)(2) formula was formed, with tetrahedral Cu coordination and anti-ferromagnetic properties. The redox processes between Cu(II) and hCys, in a molar ratio > or =1:3 led to formation of a second yellow Cu(I)hCys complex. Both Cu-hCys complexes affected the metabolism of extracellular thiols more than hCys alone and inhibited glutathione peroxidase-1 activity and mRNA abundance. The biological action of hCys and Cu-hCys complexes involved remodeling and phosphorylation of focal adhesion complexes and paxillin. The adhesive interactions of monocytes with an endothelial monolayer led to the redistribution of both paxillin and F-actin after all treatments, but the diapedesis of monocytes through endothelial cell monolayer was both greater and faster in the presence of the tentative Cu(II)(2)(hCys)(2)(H(2)O)(2) complex. Together, these observations suggest that Cu-hCys complexes actively participate in the biochemical responses of endothelial cells that are involved in the aethiopathogenesis of atherosclerosis. 相似文献
912.
Adenosine kinase deficiency is associated with developmental abnormalities and reduced transmethylation 总被引:12,自引:0,他引:12
Moffatt BA Stevens YY Allen MS Snider JD Pereira LA Todorova MI Summers PS Weretilnyk EA Martin-McCaffrey L Wagner C 《Plant physiology》2002,128(3):812-821
Adenosine (Ado) kinase (ADK; ATP:Ado 5' phosphotransferase, EC 2.7.1.20) catalyzes the salvage synthesis of adenine monophosphate from Ado and ATP. In Arabidopsis, ADK is encoded by two cDNAs that share 89% nucleotide identity and are constitutively, yet differentially, expressed in leaves, stems, roots, and flowers. To investigate the role of ADK in plant metabolism, lines deficient in this enzyme activity have been created by sense and antisense expression of the ADK1 cDNA. The levels of ADK activity in these lines range from 7% to 70% of the activity found in wild-type Arabidopsis. Transgenic plants with 50% or more of the wild-type activity have a normal morphology. In contrast, plants with less than 10% ADK activity are small with rounded, wavy leaves and a compact, bushy appearance. Because of the lack of elongation of the primary shoot, the siliques extend in a cluster from the rosette. Fertility is decreased because the stamen filaments do not elongate normally; hypocotyl and root elongation are reduced also. The hydrolysis of S-adenosyl-L-homo-cysteine (SAH) produced from S-adenosyl-L-methionine (SAM)-dependent methylation reactions is a key source of Ado in plants. The lack of Ado salvage in the ADK-deficient lines leads to an increase in the SAH level and results in the inhibition of SAM-dependent transmethylation. There is a direct correlation between ADK activity and the level of methylesterified pectin in seed mucilage, as monitored by staining with ruthenium red, immunofluorescence labeling, or direct assay. These results indicate that Ado must be steadily removed by ADK to prevent feedback inhibition of SAH hydrolase and maintain SAM utilization and recycling. 相似文献
913.
A positively charged residue of phi29 DNA polymerase, highly conserved in DNA polymerases from families A and B, is involved in binding the incoming nucleotide 下载免费PDF全文
Alignment of the protein sequence of DNA-dependent DNA polymerases has allowed the definition of a new motif, lying adjacent to motif B in the direction of the N-terminus and therefore named pre-motif B. Both motifs are located in the fingers subdomain, shown to rotate towards the active site to form a dNTP-binding pocket in several DNA polymerases in which a closed ternary complex pol:DNA:dNTP has been solved. The functional significance of pre-motif B has been studied by site-directed mutagenesis of 29 DNA polymerase. The affinity for nucleotides of 29 DNA polymerase mutant residues Ile364 and Lys371 was strongly affected in DNA- and terminal protein-primed reactions. Additionally, mutations in Ile364 affected the DNA-binding capacity of 29 DNA polymerase. The results suggest that Lys371 of 29 DNA polymerase, highly conserved among families A and B, interacts with the phosphate groups of the incoming nucleotide. On the other hand, the role of residue Ile364 seems to be structural, being important for both DNA and dNTP binding. Pre-motif B must therefore play an important role in binding the incoming nucleotide. Interestingly, the roles of Lys371 and Ile364 were also shown to be important in reactions without template, suggesting that 29 DNA polymerase can achieve the closed conformation in the absence of a DNA template. 相似文献
914.
915.
Albina ML Colomina MT Sanchez DJ Torrente M Domingo JL 《Experimental biology and medicine (Maywood, N.J.)》2002,227(9):779-785
The maternal and developmental toxicity of combined exposure to restraint stress and caffeine was assessed in mice. On gestational Days 0-18, three groups of plug-positive females (n = 13-15) were given by gavage caffeine at 30, 60, and 120 mg/kg/day. Three additional groups received the same caffeine doses and were restrained for 2 hr/day. Control groups included restrained and unrestrained plug-positive mice not exposed to caffeine. All animals in the group concurrently exposed to 120 mg/kg/day of caffeine and restraint died during the experimental period. In the remaining groups, cesarean sections were performed on Day 18 of gestation, and the fetuses were weighed and examined for external, internal, and skeletal malformations and variations. Although maternal and embryo/fetal toxicity were observed at all caffeine doses, the adverse maternal and developmental effects were significantly enhanced in the groups concurrently exposed to caffeine and restraint. It was especially remarkable at 60 and 120 mg/kg/day. The results of this study suggest that maternal and developmental toxic effects might occur if high amounts of caffeine were consumed by women under a notable stress during pregnancy. 相似文献
916.
Chahinian H Bezzine S Ferrato F Ivanova MG Perez B Lowe ME Carrière F 《Biochemistry》2002,41(46):13725-13735
The structural similarities between the C-terminal domain of human pancreatic lipase (C-HPL) and C2 domains suggested a similar function, the interaction with lipids. The catalytic N-terminal domain (N-HPL) and C-HPL were produced as individual proteins, and their partitioning between the water phase and the triglyceride-water interface was assessed using trioctanoin emulsions (TC8). N-HPL did not bind efficiently to TC8 and was inactive. C-HPL did bind to TC8 and to a phospholipid monolayer with a critical surface pressure of penetration similar to that of HPL (15 mN m(-1)). These experiments, performed in the absence of colipase and bile salts, support an absolute requirement of C-HPL for interfacial binding of HPL. To refine our analysis, we determined the contribution to lipid interactions of a hydrophobic loop (beta 5') in C-HPL by investigating a HPL mutant in which beta 5' loop hydrophobicity was increased by introducing the homologous lipoprotein lipase (LPL) beta 5' loop. This mutant (HPL-beta 5'LPL) penetrated into phospholipid monolayers at higher surface pressures than HPL, and its level of binding to TC8 was higher than that of HPL in the presence of serum albumin (BSA), an inhibitory protein that competes with HPL for interfacial adsorption. The beta 5' loop of LPL is therefore tailored for an optimal interaction with the surface of triglyceride-rich lipoproteins (VLDL and chylomicrons) containing phospholipids and apoproteins. These observations support a major contribution of the beta 5' loop in the interaction of LPL and HPL with their respective substrates. 相似文献
917.
918.
Cheng H Kartenbeck J Kabsch K Mao X Marqués M Alonso A 《Journal of cellular physiology》2002,192(2):234-243
Activation of the epidermal growth factor receptor (EGFR) has been shown to occur by ligand-dependent and ligand-independent mechanisms. Different molecular mechanisms have been found to be responsible for ligand-independent receptor transactivation. Here, we show that hyperosmolar concentrations of sorbitol activate the EGFR in human keratinocytes. Experiments using specific inhibitors of EGFR phosphorylation show that the increased amount of activated receptors is the result of a decreased rate of dephosphorylation. Furthermore, sorbitol treatment results in a strong activation of stress kinase p38. Treatment of the cells with SB203580, a known inhibitor of p38 alpha and beta kinases, results in impairment of receptor activation, indicating that the stress kinase is involved in receptor activation modulation. This is further reinforced by experiments showing that addition of Toxin B, known to be an inhibitor of the small Rho GTPases rac1, cdc42, and Rho A/B, to the cells results in a strong induction of EGFR activation. Our results point, therefore, to a mechanism by which osmotic shock activates EGFR through the small Rho GTPases-p38 stress kinase pathway. 相似文献
919.
Concha MI Santander C Villanueva J Amthauer R 《The Journal of experimental zoology》2002,293(6):541-550
In a previous study we had demonstrated that a 15-kDa protein present in carp intestinal brush-border membrane vesicles (BBMV) was able to bind the endocytosis tracer horseradish peroxidase (HRP) with high specificity. Here we show that this protein corresponds to a peripheral membrane protein, identified by partial amino acid sequence analysis as the intestinal fatty acid-binding protein (I-FABP), a member of the small cytosolic fatty acid binding protein family (FABPs). The presence of I-FABP and its HRP-binding activity was demonstrated both in the cytosolic and membrane-associated fractions of intestinal mucosa by Western and ligand blot analyses, respectively. Also, both fractions displayed significant capacity to bind [(3)H]palmitic acid, a known ligand for I-FABP. Immunohistochemical analysis showed that I-FABP localizes both in the cytosol and in the brush-border membranes of epithelial cells. Taken together the unusual extra-cellular localization of I-FABP as well as its ability to interact with HRP suggests a novel function for this protein in the intestinal mucosa. 相似文献
920.