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61.
62.
PD98059 and U0126 are organic compound inhibitors frequently used to block the activity of the MEK-1/2 protein kinase. In the present work, promoter activation analyses of xanthine oxidoreductase (XOR) in epithelial cells uncovered the unexpected opposite effect of these inhibitors on activation of XOR. Activation of an XOR-luciferase fusion gene was studied in stably transfected epithelial cells. The XOR reporter gene was activated by the epidermal growth factors (EGF), prolactin, and dexamethasone and by the acute phase cytokines (APC) IL-1, IL-6, and TNFalpha as previously reported for its native gene, and insulin further stimulated activation induced with acute phase cytokines or growth factors. Activation of the proximal promoter was blocked by inhibitors of the glucocorticoid receptor (GR), p38 MAP kinase, and U0126. Unexpectedly, PD98059 activated the promoter and significantly enhanced expression induced by insulin, APC, or growth factors. Analysis of the XOR upstream DNA and proximal promoter revealed primary roles for the GR and STAT3 in mediating the effects of PD98059 on XOR activation and protein complex formation with the promoter. STAT3 phosphotyrosine-705 was rapidly induced by PD98059, dexamethasone, and insulin. XOR activation by PD98059, dexamethasone, or insulin was superinduced by a constitutively active derivative of STAT3, while a dominant negative derivative of STAT3 blocked the enhancing effect of PD98059 on XOR activation. These data demonstrate a previously unrecognized effect of PD98059 on STAT3 and the GR that could have unanticipated consequences when used to infer the involvement of the MEK-1/2 protein kinase. 相似文献
63.
Carla Cacciotto Maria Filippa Addis Daniela Pagnozzi Bernardo Chessa Elisabetta Coradduzza Laura Carcangiu Sergio Uzzau Alberto Alberti Marco Pittau 《BMC microbiology》2010,10(1):225
Background
Mycoplasmas are the simplest bacteria capable of autonomous replication. Their evolution proceeded from gram-positive bacteria, with the loss of many biosynthetic pathways and of the cell wall. In this work, the liposoluble protein complement of Mycoplasma agalactiae, a minimal bacterial pathogen causing mastitis, polyarthritis, keratoconjunctivitis, and abortion in small ruminants, was subjected to systematic characterization in order to gain insights into its membrane proteome composition. 相似文献64.
Alzheimer's disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzyme 总被引:5,自引:0,他引:5
Eckman EA Watson M Marlow L Sambamurti K Eckman CB 《The Journal of biological chemistry》2003,278(4):2081-2084
The abnormal accumulation of beta-amyloid (Abeta) in the brain is an early and invariant feature in Alzheimer's disease (AD) and is believed to play a pivotal role in the etiology and pathogenesis of the disease. As such, a major focus of AD research has been the elucidation of the mechanisms responsible for the generation of Abeta. As with any peptide, however, the degree of Abeta accumulation is dependent not only on its production but also on its removal. In cell-based and in vitro models we have previously characterized endothelin-converting enzyme-1 (ECE-1) as an Abeta-degrading enzyme that appears to act intracellularly, thus limiting the amount of Abeta available for secretion. To determine the physiological significance of this activity, we analyzed Abeta levels in the brains of mice deficient for ECE-1 and a closely related enzyme, ECE-2. Significant increases in the levels of both Abeta40 and Abeta42 were found in the brains of these animals when compared with age-matched littermate controls. The increase in Abeta levels in the ECE-deficient mice provides the first direct evidence for a physiological role for both ECE-1 and ECE-2 in limiting Abeta accumulation in the brain and also provides further insight into the factors involved in Abeta clearance in vivo. 相似文献
65.
66.
In a synthetic route that varies from the standard procedure requiring irradiation, the (η6-C6H5Cl)Cr(CO)2PPh3 complex is obtained upon reacting (η6-C6H5Cl)Cr(CO)3 with tetrakis(triphenylphosphine)palladium(0), CuI, and trimethylsilylphenylacetylene in triethylamine. The X-ray crystal structure of the yellow–orange crystals of (η6-C6H5Cl)Cr(CO)2PPh3 allows structural comparisons to related (arene)Cr(CO)2PR3 complexes. 相似文献
67.
Hernández-SanMiguel E Vay L Santo-Domingo J Lobatón CD Moreno A Montero M Alvarez J 《Cell calcium》2006,40(1):53-61
There is increasing evidence that mitochondria play an important role in the control of cytosolic Ca2+ signaling. We show here that the main mitochondrial Ca2+-exit pathway, the mitochondrial Na+/Ca2+ exchanger, controls the pattern of cytosolic Ca2+ oscillations in non-excitable cells. In HeLa cells, the inhibitor of the mitochondrial Na+/Ca2+ exchanger CGP37157 changed the pattern of the oscillations induced by histamine from a high-frequency irregular one to a lower frequency baseline spike type, surprisingly with little changes in the average Ca2+ values of a large cell population. In human fibroblasts, CGP37157 increased the frequency of the baseline oscillations in cells having spontaneous activity and induced the generation of oscillations in cells without spontaneous activity. This effect was dose-dependent, disappeared when the inhibitor was washed out and was not mimicked by mitochondrial depolarization. CGP37157 increased mitochondrial [Ca2+] and ATP production in histamine-stimulated HeLa cells, but the effect on ATP production was only transient. CGP37157 also activated histamine-induced Ca2+ release from the endoplasmic reticulum and increased the size of the cytosolic Ca2+ peak induced by histamine in HeLa cells. Our results suggest that the mitochondrial Na+/Ca2+ exchanger directly modulates inositol 1,4,5-trisphosphate-induced Ca2+ release and in that way controls cytosolic Ca2+ oscillations. 相似文献
68.
69.
Renate L. E. P. Reniers Laura Murphy Ashleigh Lin Sandra Para Bartolomé Stephen J. Wood 《PloS one》2016,11(4)
This study investigated the influence of personality characteristics and gender on adolescents’ perception of risk and their risk-taking behaviour. Male and female participants (157 females: 116 males, aged 13–20) completed self-report measures on risk perception, risk-taking and personality. Male participants perceived behaviours as less risky, reportedly took more risks, were less sensitive to negative outcomes and less socially anxious than female participants. Path analysis identified a model in which age, behavioural inhibition and impulsiveness directly influenced risk perception, while age, social anxiety, impulsiveness, sensitivity to reward, behavioural inhibition and risk perception itself were directly or indirectly associated with risk-taking behaviour. Age and behavioural inhibition had direct relationships with social anxiety, and reward sensitivity was associated with impulsiveness. The model was representative for the whole sample and male and female groups separately. The observed relationship between age and social anxiety and the influence this may have on risk-taking behaviour could be key for reducing adolescent risk-taking behaviour. Even though adolescents may understand the riskiness of their behaviour and estimate their vulnerability to risk at a similar level to adults, factors such as anxiety regarding social situations, sensitivity to reward and impulsiveness may exert their influence and make these individuals prone to taking risks. If these associations are proven causal, these factors are, and will continue to be, important targets in prevention and intervention efforts. 相似文献
70.
Laura ConteBernard L. Trumpower Vincenzo Zara 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(1):91-101
The yeast cytochrome bc1 complex, a component of the mitochondrial respiratory chain, is composed of ten distinct protein subunits. In the assembly of the bc1 complex, some ancillary proteins, such as the chaperone Bcs1p, are actively involved. The deletion of the nuclear gene encoding this chaperone caused the arrest of the bc1 assembly and the formation of a functionally inactive bc1 core structure of about 500-kDa. This immature bc1 core structure could represent, on the one hand, a true assembly intermediate or, on the other hand, a degradation product and/or an incorrect product of assembly. The experiments here reported show that the gradual expression of Bcs1p in the yeast strain lacking this protein was progressively able to rescue the bc1 core structure leading to the formation of the functional homodimeric bc1 complex. Following Bcs1p expression, the mature bc1 complex was also progressively converted into two supercomplexes with the cytochrome c oxidase complex. The capability of restoring the bc1 complex and the supercomplexes was also possessed by the mutated yeast R81C Bcsp1. Notably, in the human ortholog BCS1L, the corresponding point mutation (R45C) was instead the cause of a severe bc1 complex deficiency. Differently from the yeast R81C Bcs1p, two other mutated Bcs1p's (K192P and F401I) were unable to recover the bc1 core structure in yeast. This study identifies for the first time a productive assembly intermediate of the yeast bc1 complex and gives new insights into the molecular mechanisms involved in the last steps of bc1 assembly. 相似文献