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排序方式: 共有433条查询结果,搜索用时 171 毫秒
151.
Pierdomenico Ruggeri Antonietta R. Farina Natalia Di Ianni Lucia Cappabianca Marzia Ragone Giulia Ianni Alberto Gulino Andrew R. Mackay 《PloS one》2014,9(4)
The developmental and stress-regulated alternative TrkAIII splice variant of the NGF receptor TrkA is expressed by advanced stage human neuroblastomas (NBs), correlates with worse outcome in high TrkA expressing unfavourable tumours and exhibits oncogenic activity in NB models. In the present study, we report that constitutive TrkAIII expression in human SH-SY5Y NB cells inhibits Rotenone, Paraquat and LY83583-induced mitochondrial free radical reactive oxygen species (ROS)-mediated death by stimulating SOD2 expression, increasing mitochondrial SOD2 activity and attenuating mitochondrial free radical ROS production, in association with increased mitochondrial capacity to produce H2O2, within the context of a more tumour stem cell-like phenotype. This effect can be reversed by the specific TrkA tyrosine kinase inhibitor , by the multi-kinase TrkA inhibitors K252a, CEP-701 and Gö6976, which inhibit SOD2 expression, and by siRNA knockdown of SOD2 expression, which restores the sensitivity of TrkAIII expressing SH-SY5Y cells to Rotenone, Paraquat and LY83583-induced mitochondrial free radical ROS production and ROS-mediated death. The data implicate the novel TrkAIII/SOD2 axis in promoting NB resistance to mitochondrial free radical-mediated death and staminality, and suggest that the combined use of TrkAIII and/or SOD2 inhibitors together with agents that induce mitochondrial free radical ROS-mediated death could provide a therapeutic advantage that may also target the stem cell niche in high TrkA expressing unfavourable NB. GW441756相似文献
152.
Sarti P Forte E Mastronicola D Giuffrè A Arese M 《Biochimica et biophysica acta》2012,1817(4):610-619
BACKGROUND: The reactions between Complex IV (cytochrome c oxidase, CcOX) and nitric oxide (NO) were described in the early 60's. The perception, however, that NO could be responsible for physiological or pathological effects, including those on mitochondria, lags behind the 80's, when the identity of the endothelial derived relaxing factor (EDRF) and NO synthesis by the NO synthases were discovered. NO controls mitochondrial respiration, and cytotoxic as well as cytoprotective effects have been described. The depression of OXPHOS ATP synthesis has been observed, attributed to the inhibition of mitochondrial Complex I and IV particularly, found responsible of major effects. SCOPE OF REVIEW: The review is focused on CcOX and NO with some hints about pathophysiological implications. The reactions of interest are reviewed, with special attention to the molecular mechanisms underlying the effects of NO observed on cytochrome c oxidase, particularly during turnover with oxygen and reductants. MAJOR CONCLUSIONS AND GENERAL SIGNIFICANCE: The NO inhibition of CcOX is rapid and reversible and may occur in competition with oxygen. Inhibition takes place following two pathways leading to formation of either a relatively stable nitrosyl-derivative (CcOX-NO) of the enzyme reduced, or a more labile nitrite-derivative (CcOX-NO(2)(-)) of the enzyme oxidized, and during turnover. The pathway that prevails depends on the turnover conditions and concentration of NO and physiological substrates, cytochrome c and O(2). All evidence suggests that these parameters are crucial in determining the CcOX vs NO reaction pathway prevailing in vivo, with interesting physiological and pathological consequences for cells. 相似文献
153.
154.
Masci A Mastronicola D Arese M Piane M De Amicis A Blanck TJ Chessa L Sarti P 《Biochimica et biophysica acta》2008,1777(1):66-73
Ataxia Telangiectasia (AT) patients are particularly sensitive to oxidative-nitrosative stress. Nitric oxide (NO) controls mitochondrial respiration via the reversible inhibition of complex IV. The mitochondrial response to NO of AT lymphoblastoid cells was investigated. Cells isolated from three patients and three intrafamilial healthy controls were selected showing within each group a normal diploid karyotype and homogeneous telomere length. Different complex IV NO-inhibition patterns were induced by varying the electron flux through the respiratory chain, using exogenous cell membrane permeable electron donors. Under conditions of high electron flux the mitochondrial NO inhibition of respiration was greater in AT than in control cells (P< or =0.05). This property appears peculiar to AT, and correlates well to the higher concentration of cytochrome c detected in the AT cells. This finding is discussed on the basis of the proposed mechanism of reaction of NO with complex IV. It is suggested that the peculiar response of AT mitochondria to NO stress may be relevant to the mitochondrial metabolism of AT patients. 相似文献
155.
156.
Bannwart LM Carter DS Cai HY Choy JC Greenhouse R Jaime-Figueroa S Iyer PS Lin CJ Lee EK Lucas MC Lynch SM Madera AM Moore A Ozboya K Raptova L Roetz R Schoenfeld RC Stein KA Steiner S Villa M Weikert RJ Zhai Y 《Bioorganic & medicinal chemistry letters》2008,18(23):6062-6066
A series of 3,3-disubstituted pyrrolidine monoamine triple reuptake inhibitors were discovered. Analogues with low nanomolar potency, good human in vitro microsomal stability and in vitro permeability, and low drug-drug interaction potential are described. One example showed in vivo anti-depressant-like effects in the mouse tail suspension assay with a minimum effective dose of 30 mg/kg i.p. 相似文献
157.
A germplasm safeguard programme was set up with 19 grapevine varieties considered as indigenous to northeastern Italy. To better estimate how genetic structure can be used to obtain a conservation perspective of local varieties, genetic variability was examined at 30 nuclear and 3 chloroplast polymorphic microsatellite loci in the native varieties plus 7 European cultivars taken as reference. The genetic profiles of all the cultivars were searched for possible parentage relationships and several suspected cases of the same variety having different names were investigated. The alleles shared at the loci suggest a parent-offspring relationship between Merlot and Cabernet Franc, 'Gruaja' and 'Negrara Veronese', and Marzemina Nera and Marzemina Bianca. Alleles at the 30 nuclear loci are consistent with Raboso Veronese being the progeny of Marzemina Bianca and Raboso Piave. Chloroplast-specific haplotypes were singled out for the first time in this indigenous germplasm and should be considered typical of the region. It is hypothesized that there are many specific haplotypes for the local varieties due to a past contribution of wild grapevine to the cultivated gene pool. The majority of investigated cultivars were demonstrated to constitute an independent source of genetic variation, and therefore a possible valuable resource of genetic traits for breeders. 相似文献
158.
Two Cases of Vaginitis Caused by Itraconazole-Resistant Saccharomyces cerevisiae and a Review of Recently Published Studies 总被引:1,自引:0,他引:1
Savini V Catavitello C Manna A Talia M Febbo F Balbinot A D'Antonio F Di Bonaventura G Celentano C Liberati M Piccolomini R D'Antonio D 《Mycopathologia》2008,166(1):47-50
Genitourinary infections caused by non-Candida yeasts are uncommon, and especially due to Saccharomyces cerevisiae. We describe the cases of two adult females with vulvovaginal infections caused by itraconazole-resistant S. cerevisiae who made a full recovery after oral fluconazole therapy. We also provide a concise review of recently published studies on this topic. 相似文献
159.
160.
Sara Batelli Diego Albani Raffaela Rametta Letizia Polito Francesca Prato Marzia Pesaresi Alessandro Negro Gianluigi Forloni 《PloS one》2008,3(4)