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111.
Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest. 总被引:23,自引:12,他引:11 下载免费PDF全文
F M Jault J M Jault F Ruchti E A Fortunato C Clark J Corbeil D D Richman D H Spector 《Journal of virology》1995,69(11):6697-6704
Human cytomegalovirus (HCMV) infection stimulates cellular DNA synthesis and causes chromosomal damage. Because such events likely affect cellular proliferation, we investigated the impact of HCMV infection on key components of the cell cycle. Early after infection, HCMV induced elevated levels of cyclin E, cyclin E-associated kinase activity, and two tumor suppressor proteins, p53 and the retinoblastoma gene product (Rb). The steady-state concentration of Rb continued to rise throughout the infection, with most of the protein remaining in the highly phosphorylated form. At early times, HCMV infection also induced cyclin B accumulation, which was associated with a significant increase in mitosis-promoting factor activity as the infection progresses. In contrast, the levels of cyclin A and cyclin A-associated kinase activity increased only at late times in the infection, and the kinetics were delayed relative to those for cyclins E and B. Analysis of the cellular DNA content in the infected cells by flow cytometry showed a progressive shift of the cells from the G1 to the S and G2/M phases of the cell cycle, leading to an accumulation of aneuploid cells at late times. We propose that these HCMV-mediated perturbations result in cell cycle arrest in G2/M. 相似文献
112.
Mareike G. Posner Abhishek Upadhyay Aisha Alsheikh Abubaker Tiago M. Fortunato Dina Vara Ilaria Canobbio Stefan Bagby Giordano Pula 《The Journal of biological chemistry》2016,291(6):2764-2776
Extracellular fibrinogen-binding protein (Efb) from Staphylococcus aureus inhibits platelet activation, although its mechanism of action has not been established. In this study, we discovered that the N-terminal region of Efb (Efb-N) promotes platelet binding of fibrinogen and that Efb-N binding to platelets proceeds via two independent mechanisms: fibrinogen-mediated and fibrinogen-independent. By proteomic analysis of Efb-interacting proteins within platelets and confirmation by pulldown assays followed by immunoblotting, we identified P-selectin and multimerin-1 as novel Efb interaction partners. The interaction of both P-selectin and multimerin-1 with Efb is independent of fibrinogen. We focused on Efb interaction with P-selectin. Excess of P-selectin extracellular domain significantly impaired Efb binding by activated platelets, suggesting that P-selectin is the main receptor for Efb on the surface of activated platelets. Efb-N interaction with P-selectin inhibited P-selectin binding to its physiological ligand, P-selectin glycoprotein ligand-1 (PSGL-1), both in cell lysates and in cell-free assays. Because of the importance of P-selectin-PSGL-1 binding in the interaction between platelets and leukocytes, we tested human whole blood and found that Efb abolishes the formation of platelet-monocyte and platelet-granulocyte complexes. In summary, we present evidence that in addition to its documented antithrombotic activity, Efb can play an immunoregulatory role via inhibition of P-selectin-PSGL-1-dependent formation of platelet-leukocyte complexes. 相似文献
113.
Serena Pagliarani Sabrina Lucchiari Gianna Ulzi Michela Ripolone Raffaella Violano Francesco Fortunato Andreina Bordoni Stefania Corti Maurizio Moggio Nereo Bresolin Giacomo P. Comi 《生物化学与生物物理学报:疾病的分子基础》2018,1864(10):3407-3417
Glycogen disease type III (GSDIII), a rare incurable autosomal recessive disorder due to glycogen debranching enzyme deficiency, presents with liver, heart and skeletal muscle impairment, hepatomegaly and ketotic hypoglycemia. Muscle weakness usually worsens to fixed myopathy and cardiac involvement may present in about half of the patients during disease. Management relies on careful follow-up of symptoms and diet. No common agreement was reached on sugar restriction and treatment in adulthood.We administered two dietary regimens differing in their protein and carbohydrate content, high-protein (HPD) and high-protein/glucose-free (GFD), to our mouse model of GSDIII, starting at one month of age. Mice were monitored, either by histological, biochemical and molecular analysis and motor functional tests, until 10?months of age.GFD ameliorated muscle performance up to 10?months of age, while HPD showed little improvement only in young mice. In GFD mice, a decreased muscle glycogen content and fiber vacuolization was observed, even in aged animals indicating a protective role of proteins against skeletal muscle degeneration, at least in some districts. Hepatomegaly was reduced by about 20%. Moreover, the long-term administration of GFD did not worsen serum parameters even after eight months of high-protein diet. A decreased phosphofructokinase and pyruvate kinase activities and an increased expression of Krebs cycle and gluconeogenesis genes were seen in the liver of GFD fed mice.Our data show that the concurrent use of proteins and a strictly controlled glucose supply could reduce muscle wasting, and indicate a better metabolic control in mice with a glucose-free/high-protein diet. 相似文献
114.
Giacomo Monzio Compagnoni Giulio Kleiner Andreina Bordoni Francesco Fortunato Dario Ronchi Sabrina Salani Marianna Guida Corrado Corti Irene Pichler Christian Bergamini Romana Fato Maria Teresa Pellecchia Annamaria Vallelunga Francesca Del Sorbo Antonio Elia Chiara Reale Barbara Garavaglia Gabriele Mora Alessio Di Fonzo 《生物化学与生物物理学报:疾病的分子基础》2018,1864(12):3588-3597
Multiple System Atrophy is a severe neurodegenerative disorder which is characterized by a variable clinical presentation and a broad neuropathological spectrum. The pathogenic mechanisms are almost completely unknown. In the present study, we established a cellular model of MSA by using fibroblasts' primary cultures and performed several experiments to investigate the causative mechanisms of the disease, with a particular focus on mitochondrial functioning.Fibroblasts' analyses (7 MSA-P, 7 MSA-C and 6 healthy controls) displayed several anomalies in patients: an impairment of respiratory chain activity, in particular for succinate Coenzyme Q reductase (p?<?0.05), and a reduction of complex II steady-state level (p?<?0.01); a reduction of Coenzyme Q10 level (p?<?0.001) and an up-regulation of some CoQ10 biosynthesis enzymes, namely COQ5 and COQ7; an impairment of mitophagy, demonstrated by a decreased reduction of mitochondrial markers after mitochondrial inner membrane depolarization (p?<?0.05); a reduced basal autophagic activity, shown by a decreased level of LC3 II (p?<?0.05); an increased mitochondrial mass in MSA-C, demonstrated by higher TOMM20 levels (p?<?0.05) and suggested by a wide analysis of mitochondrial DNA content in blood of large cohorts of patients.The present study contributes to understand the causative mechanisms of Multiple System Atrophy. In particular, the observed impairment of respiratory chain activity, mitophagy and Coenzyme Q10 biosynthesis suggests that mitochondrial dysfunction plays a crucial role in the pathogenesis of the disease. Furthermore, these findings will hopefully contribute to identify novel therapeutic targets for this still incurable disorder. 相似文献
115.
G Castaldo G Fortunato F Salvatore L Sacchetti 《The Italian journal of biochemistry》1988,37(2):111-118
The molecular nature of serum (from normal subjects and from patients affected by various hepatobiliary diseases) gamma-glutamyltranspeptidase (GGT) isoenzymes has been studied by selective lipoprotein precipitation. Some fractions co-precipitate with LDL + VLDL (pre-beta-, beta-, beta/gamma-, gamma-, and dep-GGT fractions) or with HDL (partial precipitation of alpha 1-GGT in cirrhosis). Alpha 1-GGT + alpha 2-GGT in normal subjects, and Alb-GGT did not precipitate with either of the precipitation treatments. Total GGT and its isoenzymes were stable at 4 degrees C and at -20 degrees C for at least 20 days, with the exception of Alb-GGT which at -20 degrees C decreased by 20%. The percentage of GGT associated with LDL + VLDL appeared to be a possible marker to discriminate liver tumors from cirrhosis. A cut-off value of 20 U/L of this marker yielded a diagnostic sensitivity of 87% and a diagnostic specificity of 85%. 相似文献
116.
Vincenzo Lattanzio Angela Cardinali Claudia Ruta Irene Morone Fortunato Veronica M.T. Lattanzio Vito Linsalata Nunzia Cicco 《Environmental and Experimental Botany》2009,65(1):54-62
Micropropagation of Origanum vulgare L. by shoot buds, as a potential model system for studying carbon skeleton diversion from growth to secondary metabolism as adaptive response to nutrient deficiency, has been performed. In addition, the antioxidant phenolic compounds, produced by shoots under nutritional stress or in response to exogenously added proline, have been studied. Caffeic acid, rosmarinic acid, and lithospermic acid B have been isolated in oregano shoot cultures by reversed-phase high-performance liquid chromatography, and their structures have been elucidated by tandem mass spectrometry. Both nutritional stress, which in turn causes a moderate increase of constitutive free proline, and exogenous proline affect growth and antioxidant phenolic content of oregano shoots, compared to control.The role of proline, and the associated redox cycle, as a form of metabolic signaling based on a transfer of redox potential amongst interacting cell pathways, which in turn elicit phenolic metabolism via stimulated carbon flux through oxidative pentose phosphate pathway, is discussed. Furthermore, the potential use of oregano tissue and callus cultures as a new strategy to enable the production of useful secondary metabolites on a commercial scale is also discussed. 相似文献
117.
Letizia Penolazzi Renata Vecchiatini Stefania Bignardi Elisabetta Lambertini Elena Torreggiani Alessandro Canella Tiziana Franceschetti Giorgio Calura Fortunato Vesce Roberta Piva 《Reproductive biology and endocrinology : RB&E》2009,7(1):106-7
Wharton's jelly from the umbilical cord is a noncontroversial source of mesenchymal stem cells (WJMSCs) with high plasticity,
proliferation rate and ability to differentiate towards multiple lineages. WJMSCs from different donors have been characterized
for their osteogenic potential. Although there is large evidence of WJMSCs plasticity, recently scientific debate has focused
on MSCs selection, establishing predictable elements to discriminate the cells with most promising osteoprogenitor cell potential. 相似文献
118.
Effect of L-arginine on asymmetric dimethylarginine (ADMA) or homocysteine-accelerated endothelial cell aging 总被引:4,自引:0,他引:4
Scalera F Martens-Lobenhoffer J Täger M Bukowska A Lendeckel U Bode-Böger SM 《Biochemical and biophysical research communications》2006,345(3):1075-1082
We investigated here the effect of l-arginine on asymmetric dimethylarginine (ADMA) or homocysteine-accelerated endothelial aging. Endothelial cells were cultured in medium containing 70micromol/L arginine until fourteenth passage. ADMA, dl-homocysteine, and l-arginine were replaced every 48h starting at the fourth passage. ADMA or homocysteine inhibited significantly the population doublings (PD) and accelerated the process of aging. Co-incubation with l-arginine enhanced PD, inhibited senescence associated beta-galactosidase activity, and increased telomerase activity. This effect was associated with an increase in NO synthesis and NO synthase protein expression. Furthermore, l-arginine-induced NO formation was accompanied by a reduction in oxidative stress and an increase in protein expression and enzyme activity of heme oxygenase (HO)-1. The NO synthase inhibitor l-NAME completely abolished the effect of l-arginine on ADMA or homocysteine-accelerated aging. These findings demonstrate that l-arginine prevents the onset of endothelial aging in ADMA or homocysteine-treated cells by increasing NO formation and consequently the induction of HO-1. This might provide a new strategy to delay ADMA or homocysteine-accelerated aging. 相似文献
119.
Fortunato JJ Feier G Vitali AM Petronilho FC Dal-Pizzol F Quevedo J 《Neurochemical research》2006,31(5):671-678
Malathion is a pesticide with high potential for human exposure. However, it is possible that during the malathion metabolism, there is generation of reactive oxygen species (ROS) and malathion may produce oxidative stress in intoxicated rats. The present study was therefore undertaken to determine malathion-induced lipid peroxidation (LPO), protein carbonylation and to determine whether malathion intoxication alters the antioxidant system in brain rats. Malathion was administered intraperitoneally in the acute and chronic protocols in the doses of 25, 50, 100 and 150 mg malathion/kg. The results showed that LPO in brain increased in both protocols. The increased oxidative stress resulted in an increased in the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), observed in cortex, striatum in the acute malathion protocol and hippocampus in the chronic malathion protocol. Our results demonstrated that malathion induced oxidative stress and modulated SOD and CAT activity in selective brain regions. 相似文献
120.
Loss of LIN-35, the Caenorhabditis elegans ortholog of the tumor suppressor p105Rb, results in enhanced RNA interference 总被引:2,自引:0,他引:2
Lehner B Calixto A Crombie C Tischler J Fortunato A Chalfie M Fraser AG 《Genome biology》2006,7(1):R4-10