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31.
Evidence that noradrenaline increases pyruvate dehydrogenase activity and decreases acetyl-CoA carboxylase activity in rat interscapular brown adipose tissue in vivo. 下载免费PDF全文
The rate of fatty acid synthesis in interscapular brown adipose tissue of female cold-adapted rats, as measured by the incorporation of 3H from 3H2O into tissue lipid, was decreased by about 70% after injection of noradrenaline. There was a similar decrease in the activity of acetyl-CoA carboxylase. In contrast, the proportion of pyruvate dehydrogenase in its active non-phosphorylated form was greatly increased after injection of noradrenaline. This finding suggests that the oxidation of glucose may be important in noradrenaline-induced thermogenesis in rat brown adipose tissue. 相似文献
32.
Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation 总被引:7,自引:0,他引:7
Shimaoka M Xiao T Liu JH Yang Y Dong Y Jun CD McCormack A Zhang R Joachimiak A Takagi J Wang JH Springer TA 《Cell》2003,112(1):99-111
The structure of the I domain of integrin alpha L beta 2 bound to the Ig superfamily ligand ICAM-1 reveals the open ligand binding conformation and the first example of an integrin-IgSF interface. The I domain Mg2+ directly coordinates Glu-34 of ICAM-1, and a dramatic swing of I domain residue Glu-241 enables a critical salt bridge. Liganded and unliganded structures for both high- and intermediate-affinity mutant I domains reveal that ligand binding can induce conformational change in the alpha L I domain and that allosteric signals can convert the closed conformation to intermediate or open conformations without ligand binding. Pulling down on the C-terminal alpha 7 helix with introduced disulfide bonds ratchets the beta 6-alpha 7 loop into three different positions in the closed, intermediate, and open conformations, with a progressive increase in affinity. 相似文献
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Wang LF Mehta S Weicker S Scott JA Joseph M Razavi HM McCormack DG 《Biochemical and biophysical research communications》2001,283(3):694-699
Acute lung injury is an important feature of sepsis and increased iNOS expression and NO production contribute to the pathogenesis of this syndrome. We generated bone marrow-transplanted chimeric mice with iNOS expression limited to either inflammatory or pulmonary parenchymal cells, and assessed pulmonary iNOS activity and systemic levels of NO metabolites in an endotoxemic model of sepsis. We found that while both pulmonary parenchymal cells and inflammatory cells contribute to the increased lung iNOS activity in endotoxemia, pulmonary parenchymal cells contribute to a significantly greater degree. Using measurement of plasma NO(-)(x), whole body NO production was assessed in this model. We found that the main source of NO(-)(x) was again, parenchymal cells and not inflammatory cells. This is the first study to demonstrate that most of the increased NO production in this model of endotoxemic sepsis derives from parenchymal cells rather than inflammatory cells. 相似文献
35.
Malachy McCann Barry Coyle Sinead McKay Paul McCormack Kevin Kavanagh Michael Devereux Vickie McKee Paula Kinsella Robert O'Connor Martin Clynes 《Biometals》2004,17(6):635-645
The Cu(II) and Ag(I) complexes, [Cu(phendio)3](ClO4)24H2O and [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione), are prepared in good yield by reacting phendio with the appropriate metal perchlorate salt. The X-ray crystal structure of the Ag(I) complex shows it to have a pseudo tetrahedral structure. `Metal-free' phendio and the Cu(II) and Ag(I) phendio complexes strongly inhibit the growth of the fungal pathogen Candida albicans, and are more active than their 1,10-phenanthroline analogues. The simple Ag(I) salts, AgCH3CO2, AgNO3 and AgClO4.H2O display superior anti-fungal properties compared to analogous simple Cu(II) and Mn(II) salts, suggesting that the nature of the metal ion strongly influences activity. Exposing C. albicans to `metal-free' phendio, simple Ag(I) salts and [Ag(phendio)2]ClO4 causes extensive, non-specific DNA cleavage. `Metal-free' phendio and [Ag(phendio)2]ClO4 induce gross distortions in fungal cell morphology and there is evidence for disruption of cell division. Both drugs also exhibit high anti-cancer activity when tested against cultured mammalian cells. 相似文献
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The three-dimensional reconstruction of apo-CCT-alpha-actin by cryoelectron microscopy shows that actin binds either the CCTbeta-CCTdelta or the CCTepsilon-CCTdelta subunit pairs of the chaperonin in an open and apparently quasi-native conformation. The CCT-binding sites are seen located at the tips of the two arms of actin and these same regions of actin have been implicated in CCT binding through beta-actin peptide-array screening. Three main CCT binding regions exist: actin Sites I, II, and III, which are composed of loops that are surface-exposed in native actin. Sixty-eight amino acid residues on beta-actin have been screened by mutagenesis for effects on CCT interaction in quantitative in vitro translation assays in rabbit reticulocyte lysate. Actin seems to be folding cooperatively on chaperonin, since certain mutants discriminate CCT binding from processing. Actin Site II, located at the tip of actin subdomain 4, is the major determinant for CCT binding. Site II is composed of two anti-parallel extended beta-strands, with F200-T203 and D244 contributing substantially to the binding site. The substrate recognition chemistry of CCT thus seems different from that of Group I chaperonins and probably reflects the fact that it needs to be highly specific to enable capture and folding of the actins and tubulins. 相似文献
38.
In an attempt to generate new platinum compounds that may be effective in the treatment of cancer, as well as having a lower toxicity than traditional platins and being orally viable, we are studing the synthesis and reactivity of platinum complexes of tetraazamacrocycles bearing carboxylato pendant arms. We have synthesized adducts of meso- and rac-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane-1,7-diacetic acid (L(1)H(2)). The meso-Pt(II)L(1) complex is unstable with respect to disproportionation, forming platinum metal and [meso-Pt(IV)L(1)](2+). The rac-isomer shows less tendency to disproportionate. Cyclic voltammetry suggests that the rac-Pt(II)L(1) complex undergoes two one-electron oxidations. Using bis-triazacyclononanenickel(III), [Ni(III)(tacn)(2)](3+) as an outer-sphere oxidant, the self-exchange rate for the [Pt(II/III)L](0/+) couple has been estimated at 0.034 M(-1) s(-1). 相似文献
39.
Wheatley W Yoo S Pierce M Rebentisch M Endo M Peterson I Stump M McCormack K Garcia-Guzman M Kamb A 《Biochemical genetics》2002,40(11-12):359-378
Transdominant genetic selections can yield protein fragment and peptide modulators of specific biochemical pathways. In yeast, such screens have been highly successful in targeting the MAP (mitogen-activated protein) kinase growth-control pathway. We performed a similar type of selection aimed at recovery of modulators of the mammalian MAP kinase cascade. Two pathway activators were identified, fragments of the TrkB and Raf-1 kinases. In a second selection directed at the beta-catenin growth-control pathway, three different clones encoding cadherin fragments were recovered. In neither selection were peptide inhibitors observed. We conclude that some transdominant selections in mammalian cells can readily yield high-penetrance protein fragments, but may be less amenable to isolation of peptide inhibitors. 相似文献
40.
Peter?Kosarev Klaus?FX?Mayer Christian?S?HardtkeEmail author 《Genome biology》2002,3(4):research0016.1