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61.
62.
Wong L Lieser SA Miyashita O Miller M Tasken K Onuchic JN Adams JA Woods VL Jennings PA 《Journal of molecular biology》2005,351(1):131-143
The C-terminal Src kinase (Csk) phosphorylates and down-regulates Src family tyrosine kinases. The Csk-binding protein (Cbp) localizes Csk close to its substrates at the plasma membrane, and increases the specific activity of the kinase. To investigate this long-range catalytic effect, the phosphorylation of Src and the conformation of Csk were investigated in the presence of a high-affinity phosphopeptide derived from Cbp. This peptide binds tightly to the SH2 domain and enhances Src recognition (lowers K(m)) by increasing the apparent phosphoryl transfer rate in the Csk active site, a phenomenon detected in rapid quench flow experiments. Previous studies demonstrated that the regulation of Csk activity is linked to conformational changes in the enzyme that can be probed with hydrogen-deuterium exchange methods. We show that the Cbp peptide impacts deuterium incorporation into its binding partner (the SH2 domain), and into the SH2-kinase linker and several sequences in the kinase domain, including the glycine-rich loop in the active site. These findings, along with computational data from normal mode analyses, suggest that the SH2 domain moves in a cantilever fashion with respect to the small lobe of the kinase domain, ordering the active site for catalysis. The binding of a small Cbp-derived peptide to the SH2 domain of Csk modifies these motions, enhancing Src recognition. 相似文献
63.
Leandro Freire dos Santos Ana Lucia Zanatta Vanete Thomaz Soccol Maria Fernanda Torres Sandro José Ribeiro Bonatto Rosália Rubel Carlos Ricardo Soccol 《Biotechnology and Bioprocess Engineering》2013,18(1):201-208
The ability of Pleurotus ostreatus biomass, cultived by submerged fermentation, to produce beneficial effect on lipid profile and macrophages activity during a high-fat diet (HFD) for a long-term intake was investigated. Blood samples were collected through cardiac puncture to measure the plasma cholesterol, triglycerides, low-density protein (LDL), high-density protein (HDL), aspartate aminotransferase (AST) activity, urea-blood urea nitrogen (BUN)/creatinine ratio of rats fed on an HFD for 4 months. Dosage of lipid hydroperoxides was carried out on methanolic extract of liver tissue. Peritoneal macrophages activity was evaluated in relation to the superoxide anion, hydrogen peroxide and nitric oxide production, phagocytosis and lysosomal volume. The administration of P. ostreatus significantly altered the lipid profile and oxidative stress as related to the LDL and triglycerides decrease and inhibitory effects on superoxide anion and hydrogen peroxide production. All findings of this study lead us to suggest that the P. ostreatus maybe a beneficial agent in the hyperlipidemia and atherosclerosis treatments. 相似文献
64.
Lluis JM Morales A Blasco C Colell A Mari M Garcia-Ruiz C Fernandez-Checa JC 《The Journal of biological chemistry》2005,280(5):3224-3232
Hypoxia is known to stimulate reactive oxygen species (ROS) generation. Because reduced glutathione (GSH) is compartmentalized in cytosol and mitochondria, we examined the specific role of mitochondrial GSH (mGSH) in the survival of hepatocytes during hypoxia (5% O2). 5% O2 stimulated ROS in HepG2 cells and cultured rat hepatocytes. Mitochondrial complex I and II inhibitors prevented this effect, whereas inhibition of nitric oxide synthesis with Nomega-nitro-L-arginine methyl ester hydrochloride or the peroxynitrite scavenger uric acid did not. Depletion of GSH stores in both cytosol and mitochondria enhanced the susceptibility of HepG2 cells or primary rat hepatocytes to 5% O2 exposure. However, this sensitization was abrogated by preventing mitochondrial ROS generation by complex I and II inhibition. Moreover, selective mGSH depletion by (R,S)-3-hydroxy-4-pentenoate that spared cytosol GSH levels sensitized rat hepatocytes to hypoxia because of enhanced ROS generation. GSH restoration by GSH ethyl ester or by blocking mitochondrial electron flow at complex I and II rescued (R,S)-3-hydroxy-4-pentenoate-treated hepatocytes to hypoxia-induced cell death. Thus, mGSH controls the survival of hepatocytes during hypoxia through the regulation of mitochondrial generation of oxidative stress. 相似文献
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Rodini CO Batista AC Dionísio TJ Santos CF Cunha FQ Lara VS 《Journal of molecular histology》2008,39(3):275-282
The immunopathologic and inflammatory mechanisms involved in periodontal disease (PD) include the participation of host resident,
inflammatory cells and chemical mediators. Metalloproteinases (MMPs) and nitric oxide (NO) play essential role in extracellular
matrix turnover of periodontal tissue destruction. In this study, by means of RT-PCR through semi-quantitative densitometric
scanning methods, the expression of MMPs -2 and -9 and inducible NO synthase (iNOS) was temporally and spatially investigated
during the destructive mechanisms of experimentally induced PD in rats. Samples from different periods were microscopically
analyzed and compared with the contralateral side (control). Our results showed significant expression of MMP-9 and iNOS in
tissues affected by PD, as compared with controls, three days after PD induction, simultaneously with the beginning of alveolar
bone loss. At 7 days post induction, only the MMP-9 mRNA presented a significantly higher expression, as compared with the
respective controls. Thus, in the rat ligature-induced PD, MMP-9 and iNOS might importantly participate in the early stages
of the disease, including inflammatory cell migration, tissue destruction and alveolar bone resorption. Also, we may suggest
that the exuberant presence of PMNs may be related to the important expression of iNOS and MMP-9 found at 3 days post induction. 相似文献
69.
70.
José E. Gallardo 《PloS one》2012,7(12)
The shortest common supersequence problem is a classical problem with many applications in different fields such as planning, Artificial Intelligence and especially in Bioinformatics. Due to its NP-hardness, we can not expect to efficiently solve this problem using conventional exact techniques. This paper presents a heuristic to tackle this problem based on the use at different levels of a probabilistic variant of a classical heuristic known as Beam Search. The proposed algorithm is empirically analysed and compared to current approaches in the literature. Experiments show that it provides better quality solutions in a reasonable time for medium and large instances of the problem. For very large instances, our heuristic also provides better solutions, but required execution times may increase considerably. 相似文献