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101.
The anthrax lethal factor is a multi-domain protein toxin released by Bacillus anthracis which enters cells in a process mediated by the protective antigen and specific cell receptors. In the cytosol, the lethal factor cleaves the N-terminal tail of many MAPK kinases, thus deranging a major cell signaling pathway. The structural features at the basis of these activities of LF are reviewed here with particular attention to the proteolytic activity and to the identification of specific inhibitors. A significant similarity between the metalloprotease domain of the lethal factor and of that of the clostridial neurotoxins has been noted and is discussed. 相似文献
102.
103.
Laura Costarelli Elisa Muti Marco Malavolta Catia Cipriano Robertina Giacconi Silvia Tesei Francesco Piacenza Sara Pierpaoli Nazzarena Gasparini Emanuela Faloia Giacomo Tirabassi Marco Boscaro Angela Polito Beatrice Mauro Francesca Maiani Anna Raguzzini Fiorella Marcellini Cinzia Giuli Roberta Papa Monica Emanuelli Eugenio Mocchegiani 《The Journal of nutritional biochemistry》2010,21(5):432-437
Overweight and obesity are associated with low grade of inflammation and chronic inflammatory response characterized by abnormal production and activation of some pro-inflammatory signalling pathways. Taking into account that obesity is the direct result of an imbalance between energy intake and energy expenditure, the nutritional factors in the diet, with particular focus on zinc, may play a pivotal role in the development of obesity-associated comorbidities. Considering the potential interactions among zinc nutritional status, inflammation, overweight/obesity and insulin secretion, the aim of the present work was to clarify the influence of zinc dietary intake on some metabolic, inflammatory and zinc status parameters in adult overweight/obese subjects. We found a close interrelationship between nutritional zinc and obesity. In particular, subjects with a lower zinc dietary intake display a deeper inflammatory status, general impairment of the zinc status, an altered lipid profile and increased insulin production with respect to obese subjects with normal zinc dietary intake. Moreover, in the presence of low dietary zinc intake, the obese subjects are less capable to respond to oxidative stress and to inflammation leading to the development of obesity or to a worsening of already preexisting obesity status. In conclusion, a possible zinc supplementation in obese subjects with a deeper inflammatory status and more altered zinc profile may be suggested in order to limit or reduce the inflammation, taking also into account that zinc supplementation normalizes “inflammaging” as well as zinc profile leading to a correct intra- and extracellular zinc homeostasis. 相似文献
104.
Beatrice Cobucci-Ponzano Fiorella Conte Andrea Strazzulli Clemente Capasso Immacolata Fiume Gabriella Pocsfalvi Mosè Rossi Marco Moracci 《Biochimie》2010
α-Mannosidases, important enzymes in the N-glycan processing and degradation in Eukaryotes, are frequently found in the genome of Bacteria and Archaea in which their function is still largely unknown. The α-mannosidase from the hyperthermophilic Crenarchaeon Sulfolobus solfataricus has been identified and purified from cellular extracts and its gene has been cloned and expressed in Escherichia coli. The gene, belonging to retaining GH38 mannosidases of the carbohydrate active enzyme classification, is abundantly expressed in this Archaeon. The purified α-mannosidase activity depends on a single Zn2+ ion per subunit is inhibited by swainsonine with an IC50 of 0.2 mM. The molecular characterization of the native and recombinant enzyme, named Ssα-man, showed that it is highly specific for α-mannosides and α(1,2), α(1,3), and α(1,6)-d-mannobioses. In addition, the enzyme is able to demannosylate Man3GlcNAc2 and Man7GlcNAc2 oligosaccharides commonly found in N-glycosylated proteins. More interestingly, Ssα-man removes mannose residues from the glycosidic moiety of the bovine pancreatic ribonuclease B, suggesting that it could process mannosylated proteins also in vivo. This is the first evidence that archaeal glycosidases are involved in the direct modification of glycoproteins. 相似文献
105.
Eugenio Mocchegiani Marco Malavolta Fiorella Marcellini Graham Pawelec 《Immunity & ageing : I & A》2006,3(1):6-8
The relevance of zinc for proper functioning of the entire immune system is already well documented. However, the identification
of individuals who really need zinc supplementation is still debated in view of the fact that excessive zinc may also be toxic.
The risk of developing zinc deficiency in people from industrialized countries is relatively low, except for elderly subjects
where zinc intake may be suboptimal and inflammation is chronic. Thus, the role of zinc on the immune system and on the health
of European elderly people is becoming of paramount importance, considering also that the elderly population is rapidly increasing.
In particular, the factors contributing to and the biochemical markers of zinc deficiency in the elderly are still remain
to be established. Epidemiological, functional, and genetic studies aimed at formulating a rationale for the promotion of
healthy ageing through zinc supplementation was the subject of an International Conference held in Madrid from 11–13 February
2006 (3rd ZincAge Meeting) at the CNIO Institute (local organizer: Maria Blasco, partner of ZincAge) 相似文献
106.
Yoder JA Hanson PE Zettler LW Benoit JB Ghisays F Piskin KA 《Applied and environmental microbiology》2003,69(8):4994-4996
Scopulariopsis brevicaulis, the anamorph of Microascus brevicaulis (Microascaceae, Ascomycota), has been identified in the body contents of the tick Dermacentor variabilis. After topical application of the fungal inoculum, tick mortality was marked. This is the first account describing the internal mycoflora of D. variabilis with a novel technique used to recover potential biological control agents. 相似文献
107.
PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects 总被引:11,自引:0,他引:11
Patrucco E Notte A Barberis L Selvetella G Maffei A Brancaccio M Marengo S Russo G Azzolino O Rybalkin SD Silengo L Altruda F Wetzker R Wymann MP Lembo G Hirsch E 《Cell》2004,118(3):375-387
The G protein-coupled, receptor-activated phosphoinositide 3-kinase gamma (PI3Kgamma) mediates inflammatory responses and negatively controls cardiac contractility by reducing cAMP concentration. Here, we report that mice carrying a targeted mutation in the PI3Kgamma gene causing loss of kinase activity (PI3KgammaKD/KD) display reduced inflammatory reactions but no alterations in cardiac contractility. We show that, in PI3KgammaKD/KD hearts, cAMP levels are normal and that PI3Kgamma-deficient mice but not PI3KgammaKD/KD mice develop dramatic myocardial damage after chronic pressure overload induced by transverse aortic constriction (TAC). Finally, our data indicate that PI3Kgamma is an essential component of a complex controlling PDE3B phosphodiesterase-mediated cAMP destruction. Thus, cardiac PI3Kgamma participates in two distinct signaling pathways: a kinase-dependent activity that controls PKB/Akt as well as MAPK phosphorylation and contributes to TAC-induced cardiac remodeling, and a kinase-independent activity that relies on protein interactions to regulate PDE3B activity and negatively modulates cardiac contractility. 相似文献
108.
Pastore A Mozzi AF Tozzi G Gaeta LM Federici G Bertini E Lo Russo A Mannucci L Piemonte F 《Analytical biochemistry》2003,312(2):85-90
Since glutathionyl-hemoglobin has been suggested to be a clinical marker of oxidative stress in human blood and given the growing biological relevance of oxidative stress as a pathogenic factor in several diseases, we describe a method to measure glutathionyl-hemoglobin concentration in erythrocytes, by using cation-exchange high-pressure liquid chromatography with UV detection. The glutathionyl-hemoglobin peak has been identified on the basis of the following findings: (a) the peak increased when the sample was incubated with oxidized glutathione; (b) the peak disappeared when the sample was reduced with dithiothreitol, with the simultaneous increase of that corresponding to hemoglobin A(0); (c) the peak could be detected by incubating hemoglobin A(0) with reduced glutathione; (e) deconvoluted mass spectrum of the glutathionyl-hemoglobin peak showed a 16172.0-Da molecular mass, corresponding to hemoglobin beta bound to glutathione. Glutathionyl-hemoglobin concentration has been determined in erythrocytes of 40 healthy subjects, with a mean value of 2.58+/-0.7%, calculated as the percentage of its peak area ratio to that of total hemoglobin (HbA(0)+HbA(2)+HbA(1C)+glutathionyl-hemoglobin). The availability of a simple and reproducible method to detect glutathionyl-hemoglobin concentration in blood could be useful in monitoring oxidative stress, and for investigating the efficacy of antioxidant therapies in clinical trials. 相似文献
109.
Karyotype instability and anchorage-independent growth in telomerase-immortalized fibroblasts from two centenarian individuals 总被引:3,自引:0,他引:3
Mondello C Chiesa M Rebuzzini P Zongaro S Verri A Colombo T Giulotto E D'Incalci M Franceschi C Nuzzo F 《Biochemical and biophysical research communications》2003,308(4):914-921
Several reports have shown that the ectopic expression of the human telomerase catalytic subunit gene (hTERT) leads to an indefinite extension of the life span of human fibroblasts cultured in vitro without the appearance of cancer-associated changes. We infected two fibroblast strains derived from centenarian individuals with an hTERT containing retrovirus and isolated transduced massive populations (cen2tel and cen3tel). In both populations, hTERT expression reconstituted telomerase activity and extended the life span. In cen2tel, a net telomere lengthening was observed while, in cen3tel, telomeres stabilized at a length lower than that detected in senescent parental cells. Interestingly, both cen2tel and cen3tel cells developed chromosome anomalies, numerical first and structural thereafter. Moreover, cen3tel cells acquired the ability to grow in the absence of solid support, a typical feature of transformed cells. The results we present here highlight an unexpected possible outcome of cellular immortalization driven by telomerase reactivation, and indicate that, in some cases, an artificial extension of cellular replicative capacity can increase the probability of occurrence of genomic alterations, which can lead to cellular transformation. 相似文献
110.
Defective dendrite elongation but normal fertility in mice lacking the Rho-like GTPase activator Dbl 下载免费PDF全文
Hirsch E Pozzato M Vercelli A Barberis L Azzolino O Russo C Vanni C Silengo L Eva A Altruda F 《Molecular and cellular biology》2002,22(9):3140-3148
Dbl is the prototype of a large family of GDP-GTP exchange factors for small GTPases of the Rho family. In vitro, Dbl is known to activate Rho and Cdc42 and to induce a transformed phenotype. Dbl is specifically expressed in brain and gonads, but its in vivo functions are largely unknown. To assess its role in neurogenesis and gametogenesis, targeted deletion of the murine Dbl gene was accomplished in embryonic stem cells. Dbl-null mice are viable and did not show either decreased reproductive performances or obvious neurological defects. Histological analysis of mutant testis showed normal morphology and unaltered proliferation and survival of spermatogonia. Dbl-null brains indicated a correct disposition of the major neural structures. Analysis of cortical stratification indicated that Dbl is not crucial for neuronal migration. However, in distinct populations of Dbl-null cortical pyramidal neurons, the length of dendrites was significantly reduced, suggesting a role for Dbl in dendrite elongation. 相似文献