共查询到20条相似文献,搜索用时 15 毫秒
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Marzia Fumagalli Francesca Rossiello Chiara Mondello Fabrizio d’Adda di Fagagna 《PloS one》2014,9(10)
The DNA damage response (DDR) is activated upon DNA damage generation to promote DNA repair and inhibit cell cycle progression in the presence of a lesion. Cellular senescence is a permanent cell cycle arrest characterized by persistent DDR activation. However, some reports suggest that DDR activation is a feature only of early cellular senescence that is then lost with time. This challenges the hypothesis that cellular senescence is caused by persistent DDR activation. To address this issue, we studied DDR activation dynamics in senescent cells. Here we show that normal human fibroblasts retain DDR markers months after replicative senescence establishment. Consistently, human fibroblasts from healthy aged donors display markers of DDR activation even three years in culture after entry into replicative cellular senescence. However, by extending our analyses to different human cell strains, we also observed an apparent DDR loss with time following entry into cellular senescence. This though correlates with the inability of these cell strains to survive in culture upon replicative or irradiation-induced cellular senescence. We propose a model to reconcile these results. Cell strains not suffering the prolonged in vitro culture stress retain robust DDR activation that persists for years, indicating that under physiological conditions persistent DDR is causally involved in senescence establishment and maintenance. However, cell strains unable to maintain cell viability in vitro, due to their inability to cope with prolonged cell culture-associated stress, show an only-apparent reduction in DDR foci which is in fact due to selective loss of the most damaged cells. 相似文献
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真核细胞中,一定数量和种类的TBP相关因子与TBP结合成多蛋白复合物--基本起始因子SL1、TFⅡD、TFⅢB,分别指导三类基因的转录.因此,TBP是一种通用转录因子,而TAFs则具有聚合酶和启动子特异性,起辅助转录激活因子的作用.在转录起始过程中,前者在种属间高度保守的C端独特结构可直接识别TATA元件,或通过TAFs与DNA结合;而后者有的作为TBP结合DNA的媒介,有的作为转录起始复合物组装时其他TAFs与TBP相互作用的桥梁,有的则作为转录激活蛋白与TBP联系的纽带,介导转录激活蛋白对基因转录的激活作用. 相似文献
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Linda L. Werling †Paul J. Hoehner K. Joseph Hurt Laura G. Fox †Thomas J. J. Blanck Robert E. Rosenthal Gary Fiskum 《Journal of neurochemistry》1994,63(1):215-221
Abstract: We investigated the relationships among N -methyl- d -aspartate, glycine, L-type voltage-dependent calcium channels, and [3 H]dopamine release in a canine model of global cerebral ischemia/reperfusion. The binding of [3 H]PN200-110 ([3 H]isradipine) to L-type voltage-dependent calcium channels, that open as a consequence of N -methyl- d -aspartate-induced changes in membrane potential, was approximately doubled in striatal membranes prepared from ischemic animals relative to controls, and remained significantly elevated at 30 min and 2 h of reperfusion. These changes coincided temporally with changes in the ability of the voltage-sensitive calcium channel blocker nitrendipine to inhibit glycine enhancement of N -methyl- d -aspartate-stimulated [3 H]dopamine release in striatal slices prepared from the same animals. Compared with nonischemic controls, N -methyl- d -aspartate-stimulated [3 H]dopamine release was increased in ischemic animals and remained increased throughout reperfusion up to at least 24 h. Glycine enhanced N -methyl- d -aspartate-stimulated release in all treatment groups. The enhancement of N -methyl- d -aspartate-stimulated dopamine release by glycine was reduced by the inclusion of nitrendipine in striatal slices from ischemic and 30-min reperfused animals. These data suggest that glycine may facilitate opening of the voltage-dependent calcium channels activated by N -methyl- d -aspartate and that this facilitation is blocked by the antagonist nitrendipine. 相似文献
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Weiyuan Wang Qiuyuan Wen Lina Xu Guiyuan Xie Jiao Li Jiadi Luo Shuzhou Chu Lei Shi Donghai Huang Jinghe Li Songqing Fan 《PloS one》2014,9(8)
Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck region, which frequently occurs in Southeast Asia, especially in the south of China. It is known that the mammalian target of rapamycin (mTOR) pathway plays a central role in regulating cellular functions, including proliferation, growth, survival, mobility, and angiogenesis. Aberrant expression of the mTOR signaling pathway molecules has been found in many types of cancer. However, whether the alterations of p-Akt, p-p70S6K and p-4EBP1 protein expression are associated with clinicopathological features and prognostic implications in NPC have not been reported. The purposes of the present study are to investigate the association between the expression of p-Akt, p-p70S6K and p-4EBP1 proteins and clinicopathological features in NPC by immunohistochemistry. The results showed that the positive percentage of p-Akt, p-p70S6K and p-4EBP1 proteins expression in NPC (47.2%, 73.0% and 61.7%, respectively) was significantly higher than that in the non-cancerous nasopharyngeal control tissue (33.3%, 59.1% and 47.0%, respectively). There was a significantly higher positive expression of p-Akt in undifferentiated non-keratinizing nasopharyngeal carcinoma than that in differentiated non-keratinizing nasopharyngeal carcinoma (P = 0.014). Additionally, positive expression of p-p70S6K and p-4EBP1 proteins, and positive expression of either of p-Akt, p-p70S6K and p-4EBP1 were significantly correlated inversely with overall survival rates of NPC patients (P = 0.023, P = 0.033, P = 0.008, respectively). Spearman’s rank correlation test showed that expression of p-Akt in NPC was significantly associated with expression of p-p70S6K (r = 0.263, P<0.001) and p-4EBP1(r = 0.284, P<0.001). Also there was an obviously positive association between expression of p-p70S6K and p-4EBP1 proteins in NPC (r = 0.286, P<0.001). Multivariate Cox regression analysis further identified positive expression of p-4EBP1 and p-p70S6K proteins were the independent poor prognostic factors for NPC (P = 0.043, P = 0.027, respectively). Taken together, high expression of p-p70S6K and p-4EBP1 proteins may act as valuable independent biomarkers to predict a poor prognosis of NPC. 相似文献
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Elizabeth Buescher Tilman Achberger Idris Amusan Anthony Giannini Cherie Ochsenfeld Ana Rus Brett Lahner Owen Hoekenga Elena Yakubova Jeffrey F. Harper Mary Lou Guerinot Min Zhang David E. Salt Ivan R. Baxter 《PloS one》2010,5(6)
Controlling elemental composition is critical for plant growth and development as well as the nutrition of humans who utilize plants for food. Uncovering the genetic architecture underlying mineral ion homeostasis in plants is a critical first step towards understanding the biochemical networks that regulate a plant''s elemental composition (ionome). Natural accessions of Arabidopsis thaliana provide a rich source of genetic diversity that leads to phenotypic differences. We analyzed the concentrations of 17 different elements in 12 A. thaliana accessions and three recombinant inbred line (RIL) populations grown in several different environments using high-throughput inductively coupled plasma- mass spectroscopy (ICP-MS). Significant differences were detected between the accessions for most elements and we identified over a hundred QTLs for elemental accumulation in the RIL populations. Altering the environment the plants were grown in had a strong effect on the correlations between different elements and the QTLs controlling elemental accumulation. All ionomic data presented is publicly available at www.ionomicshub.org. 相似文献
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Raffaella Colombatti Emiliano De Bon Antonella Bertomoro Alessandra Casonato Elena Pontara Elisabetta Omenetto Graziella Saggiorato Agostino Steffan Tamara Damian Giuseppe Cella Simone Teso Renzo Manara Patrizia Rampazzo Giorgio Meneghetti Giuseppe Basso Maria Teresa Sartori Laura Sainati 《PloS one》2013,8(10)
Background
Thrombotic complications in Sickle Cell Disease (SCD) arise since infancy, but the role of the coagulation system in children has been poorly explored. To determine its role in the development of clinical complications in childhood we measured coagulation and endothelial parameters in children with SCD at steady state.Methods
Markers of thrombin generation, fibrin dissolution and endothelial activation were evaluated in 38 children with SS-Sβ°, 6 with SC disease and 50 age and blood group matched controls. Coagulation variables were correlated with markers of hemolysis and inflammation, with the presence of cerebral and lung vasculopathy and with the frequency of clinical complications.Results
SS-Sβ° patients presented higher levels of factor VIII, von Willebrand factor antigen (VWF:Ag) and collagen binding activity, tissue plasminogen activator antigen (t-PA:Ag), D-dimer, p-selectin, prothrombin fragment1+2 (F1+2) and lower ADAMTS-13:activity/VWF:Ag (p<0.05) compared to controls and SC patients. In SS-Sβ° patients coagulation variables correlated positively with markers of inflammation, hemolysis, and negatively with HbF (p<0.05). Patients with cerebral silent infarcts showed significant decrease in t-PA:Ag and ADAMTS-13 Antigen and a tendency toward higher D-dimer, F1+2, TAT compared to patients without them. D-dimer was associated with a six fold increased risk of cerebral silent infarcts. No correlation was found between coagulation activation and large vessel vasculopathy or other clinical events except for decreased t-PA:Ag in patients with tricuspid Rigurgitant Velocity >2.5m/sec.Conclusions
SS-Sβ° disease is associated with extensive activation of the coagulation system at steady state since young age. ADAMTS-13 and t-PA:Ag are involved in the development of cerebral silent infarcts. 相似文献18.
The Non-JAZ TIFY Protein TIFY8 from Arabidopsis thaliana Is a Transcriptional Repressor 总被引:1,自引:0,他引:1
Amparo Cuéllar Pérez Astrid Nagels Durand Robin Vanden Bossche Rebecca De Clercq Geert Persiau Saskia C. M. Van Wees Corné M. J. Pieterse Kris Gevaert Geert De Jaeger Alain Goossens Laurens Pauwels 《PloS one》2014,9(1)
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Cornelia A. M. van de Weg Ralph M. H. G. Huits Cláudio S. Pannuti Rosalba M. Brouns Riemsdijk W. A. van den Berg Henk-Jan van den Ham Byron E. E. Martina Albert D. M. E. Osterhaus Mihai G. Netea Joost C. M. Meijers Eric C. M. van Gorp Esper G. Kallas 《PLoS neglected tropical diseases》2014,8(10)