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21.
Ruffolo SC Forsell PK Yuan X Desmarais S Himms-Hagen J Cromlish W Wong KK Kennedy BP 《The Journal of biological chemistry》2007,282(42):30423-30433
Although protein-tyrosine phosphatase 1B (PTP-1B) is a negative regulator of insulin action, adipose tissue from PTP-1B-/- mice does not show enhanced insulin-stimulated insulin receptor phosphorylation. Investigation of glucose uptake in isolated adipocytes revealed that the adipocytes from PTP-1B-/- mice have a significantly attenuated insulin response as compared with PTP-1B+/+ adipocytes. This insulin resistance manifests in PTP-1B-/- animals older than 16 weeks of age and could be partially rescued by adenoviral expression of PTP-1B in null adipocytes. Examination of adipose signaling pathways found that the basal p70S6K activity was at least 50% higher in adipose from PTP-1B-/- mice compared with wild type animals. The increased basal activity of p70S6K in PTP-1B-/- adipose correlated with decreases in IR substrate-1 protein levels and insulin-stimulated Akt/protein kinase B activity, explaining the decrease in insulin sensitivity even as insulin receptor phosphorylation was unaffected. The insulin resistance of the of the PTP-1B-/- adipocytes could also be rescued by treatment with rapamycin, suggesting that in adipose the loss of PTP-1B results in basal activation of mTOR (mammalian target of rapamycin) complex 1 leading to a tissue-specific insulin resistance. 相似文献
22.
Boström J Berggren K Elebring T Greasley PJ Wilstermann M 《Bioorganic & medicinal chemistry》2007,15(12):4077-4084
A scaffold hopping approach has been exploited to design a novel class of cannabinoid (CB1) receptor antagonists for the treatment of obesity. On the basis of shape-complementarity and synthetic feasibility the central fragment, a methylpyrazole, in Rimonabant was replaced by a pyrazine. The synthesis and CB1 antagonistic activities of a new series of 5,6-diaryl-pyrazine-2-amide derivatives are described. Several compounds showed antagonist potency below 10nM for the CB1 receptor. 相似文献
23.
Isolation and gene quantification of heterotrophic N2-fixing bacterioplankton in the Baltic Sea 总被引:1,自引:0,他引:1
Cyanobacteria are regarded as the main N(2)-fixing organisms in marine waters. However, recent clone libraries from various oceans show a wide distribution of the dinitrogenase reductase gene (nifH) originating from heterotrophic bacterioplankton. We isolated heterotrophic N(2)-fixing bacteria from Baltic Sea bacterioplankton using low-nitrogen plates and semi-solid diazotroph medium (SSDM) tubes. Isolates were analysed for the nitrogenase (nifH) gene and active N(2) fixation by nested polymerase chain reaction (PCR) and acetylene reduction respectively. A primer-probe set targeting the nifH gene from a gamma-proteobacterial isolate, 97% 16S rDNA similarity to Pseudomonas stutzeri, was designed for measuring in situ dynamics using quantitative real-time PCR. This nifH gene sequence was detected at two of 11 stations in a Baltic Proper transect at abundances of 3 x 10(4) and 0.8 x 10(3) copies per litre seawater respectively. Oxygen requirements of isolates were examined by cultivation in SSDM tubes where oxygen gradients were determined with microelectrodes. Growth, and thereby N(2) fixation, was observed as horizontal bands formed at oxygen levels of 0-6% air saturation. The apparent microaerophilic or facultative anaerobic nature of the isolates explains why the SSDM approach is the most appropriate isolation method. Our study illustrates how combined isolation, functional analyses and in situ quantification yielded insights into the oxygen requirements of heterotrophic N(2)-fixing bacterioplankton isolates, which were confirmed to be present in situ. 相似文献
24.
SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity 总被引:3,自引:0,他引:3
Boström P Andersson L Rutberg M Perman J Lidberg U Johansson BR Fernandez-Rodriguez J Ericson J Nilsson T Borén J Olofsson SO 《Nature cell biology》2007,9(11):1286-1293
The accumulation of cytosolic lipid droplets in muscle and liver cells has been linked to the development of insulin resistance and type 2 diabetes. Such droplets are formed as small structures that increase in size through fusion, a process that is dependent on intact microtubules and the motor protein dynein. Approximately 15% of all droplets are involved in fusion processes at a given time. Here, we show that lipid droplets are associated with proteins involved in fusion processes in the cell: NSF (N-ethylmaleimide-sensitive-factor), alpha-SNAP (soluble NSF attachment protein) and the SNAREs (SNAP receptors), SNAP23 (synaptosomal-associated protein of 23 kDa), syntaxin-5 and VAMP4 (vesicle-associated membrane protein 4). Knockdown of the genes for SNAP23, syntaxin-5 or VAMP4, or microinjection of a dominant-negative mutant of alpha-SNAP, decreases the rate of fusion and the size of the lipid droplets. Thus, the SNARE system seems to have an important role in lipid droplet fusion. We also show that oleic acid treatment decreases the insulin sensitivity of heart muscle cells, and this sensitivity is completely restored by transfection with SNAP23. Thus, SNAP23 might be a link between insulin sensitivity and the inflow of fatty acids to the cell. 相似文献
25.
26.
Background
Stem cells reside in a plant's shoot meristem throughout its life and are main regulators of above-ground plant development. The stem cell maintenance depends on a feedback network between the CLAVATA and WUSCHEL genes. The CLAVATA3 peptide binds to the CLAVATA1 receptor leading to WUSCHEL inhibition. WUSCHEL, on the other hand, activates CLAVATA3 expression. Recent experiments suggest a second pathway where CLAVATA3 inhibits WUSCHEL via the CORYNE receptor pathway. An interesting question, central for understanding the receptor signaling, is why the clavata1-11 null mutant has a weaker phenotype compared with the clavata1-1 non-null mutant. It has been suggested that this relies on interference from the mutated CLAVATA1 acting on the CORYNE pathway. 相似文献27.
28.
Boström M Tavares FW Finet S Skouri-Panet F Tardieu A Ninham BW 《Biophysical chemistry》2005,117(3):217-224
The relative effectiveness of different anions in crystallizing proteins follows a reversed Hofmeister sequence for pHpI. The phenomenon has been known almost since Hofmeister's original work but it has not been understood. It is here given a theoretical explanation. Classical electrolyte and double layer theory deals only with electrostatic forces acting between ions and proteins. Hydration and hydration interactions are dealt with usually only in terms of assumed hard core models. But there are, at and above biological salt concentrations, other non-electrostatic (NES) ion-specific forces acting that are ignored in such modeling. Such electrodynamic fluctuation forces are also responsible for ion-specific hydration. These missing forces are variously comprehended under familiar but generally unquantified terms, typically, hydration, hydrogen bonding, pi-electron-cation interactions, dipole-dipole, dipole-induced dipole and induced dipole-induced dipole forces and so on. The many important body electrodynamic fluctuation force contributions are accessible from extensions of Lifshitz theory from which, with relevant dielectric susceptibility data on solutions as a function of frequency, the forces can be extracted quantitatively, at least in principle. The classical theories of colloid science that miss such contributions do not account for a whole variety of ion-specific phenomena. Numerical results that include these non-electrostatic forces are given here for model calculations of the force between two model charge-regulated hen-egg-white protein surfaces. The surfaces are chosen to carry the same charge groups and charge density as the protein. What emerges is that for pHpI (where anions are co-ions) the forces increase in the order NaCl相似文献
29.
30.
Boström M Markland K Sandén AM Hedhammar M Hober S Larsson G 《Applied microbiology and biotechnology》2005,68(1):82-90
The effect of changes in substrate feed rate during fedbatch cultivation was investigated with respect to soluble protein formation and transport of product to the periplasm in Escherichia coli. Production was transcribed from the PmalK promoter; and the cytoplasmic part of the production was compared with production from the PlacUV5 promoter. The fusion protein product, Zb-MalE, was at all times accumulated in the soluble protein fraction except during high-feed-rate production in the cytoplasm. This was due to a substantial degree of proteolysis in all production systems, as shown by the degradation pattern of the product. The product was also further subjected to inclusion body formation. Production in the periplasm resulted in accumulation of the full-length protein; and this production system led to a cellular physiology where the stringent response could be avoided. Furthermore, the secretion could be used to abort the diauxic growth phase resulting from use of the PmalK promoter. At high feed rate, the accumulation of acetic acid, due to overflow metabolism, could furthermore be completely avoided. 相似文献