排序方式: 共有100条查询结果,搜索用时 15 毫秒
61.
Calabrese V Giuffrida Stella AM Calvani M Butterfield DA 《The Journal of nutritional biochemistry》2006,17(2):73-88
Aging is associated with a reduced ability to cope with physiological challenges. Although the mechanisms underlying age-related alterations in stress tolerance are not well defined, many studies support the validity of the oxidative stress hypothesis, which suggests that lowered functional capacity in aged organisms is the result of an increased generation of reactive oxygen and nitrogen species. Increased production of oxidants in vivo can cause damage to intracellular macromolecules, which can translate into oxidative injury, impaired function and cell death in vulnerable tissues such as the brain. To survive different types of injuries, brain cells have evolved networks of responses, which detect and control diverse forms of stress. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of several genes termed vitagenes. Among these, heat shock proteins form a highly conserved system responsible for the preservation and repair of the correct protein conformation. The heat shock response contributes to establishing a cytoprotective state in a wide variety of human diseases, including inflammation, cancer, aging and neurodegenerative disorders. Given the broad cytoprotective properties of the heat shock response, there is now a strong interest in discovering and developing pharmacological agents capable of inducing the heat shock response. Acetylcarnitine is proposed as a therapeutic agent for several neurodegenerative disorders, and there is now evidence that it may play a critical role as modulator of cellular stress response in health and disease states. In the present review, we first discuss the role of nutrition in carnitine metabolism, followed by a discussion of carnitine and acetyl-l-carnitine in mitochondrial dysfunction, in aging, and in age-related disorders. We then review the evidence for the role of acetylcarnitine in modulating redox-dependent mechanisms leading to up-regulation of vitagenes in brain, and we also discuss new approaches for investigating the mechanisms of lifetime survival and longevity. 相似文献
62.
Viparelli F Doti N Sandomenico A Marasco D Dathan NA Miele C Beguinot F Monti SM Ruvo M 《Protein expression and purification》2008,59(2):302-308
PLD’s (Phospholipases D) are ubiquitously expressed proteins involved in many transphosphatidylation reactions. They have a bi-lobed structure composed by two similar domains which at their interface reconstitute the catalytic site through the association of the two conserved HxKx4Dx6GSxN motifs. PLD1 interacts with the small phosphoprotein PED-PEA15 by an unknown mechanism that, by enhancing PLD1 stability, apparently increases its enzymatic activity; the minimum interacting region of PLD1 was previously identified as spanning residues 712–1074 (D4 region). Since the D4/PED-PEA15 interaction has been claimed to be one of the multiple molecular events that can trigger type 2 diabetes, we purified the two recombinant proteins to study in vitro this binding by both ELISA and SPR techniques. Whilst PED-PEA15 was easily expressed and purified, expression of recombinant D4 was more problematic and only the fusion protein with Thioredoxin A and a six Histidine Tag (Trx-His6-D4) demonstrated sufficient stability for further characterization. We have found that Trx-His6-D4 is present as two different oligomeric forms, though only the monomeric variant is able to interact with PED-PEA15. All these findings may have important implications for both the mechanisms of phospholipase activity and PED-PEA15 regulative functions. 相似文献
63.
Jean Menotti Alexandra Emmanuel Chafia Bouchekouk Magali Chabe Firas Choukri Muriel Pottier Claudine Sarfati El Moukhtar Aliout Francis Derouin 《PloS one》2013,8(4)
To better understand the role of immunocompetent hosts in the diffusion of Pneumocystis in the environment, airborne shedding of Pneumocystis carinii in the surrounding air of experimentally infected Sprague Dawley rats was quantified by means of a real-time PCR assay, in parallel with the kinetics of P. carinii loads in lungs and specific serum antibody titres. Pneumocystis-free Sprague Dawley rats were intratracheally inoculated at day 0 (d0) and then followed for 60 days. P. carinii DNA was detected in lungs until d29 in two separate experiments and thereafter remained undetectable. A transient air excretion of Pneumocystis DNA was observed between d14 and d22 in the first experiment and between d9 and d19 in the second experiment; it was related to the peak of infection in lungs. IgM and IgG anti-P. carinii antibody increase preceded clearance of P. carinii in the lungs and cessation of airborne excretion. In rats receiving a second challenge 3 months after the first inoculation, Pneumocystis was only detected at a low level in the lungs of 2 of 3 rats at d2 post challenge and was never detected in air samples. Anti-Pneumocystis antibody determinations showed a typical secondary IgG antibody response. This study provides the first direct evidence that immunocompetent hosts can excrete Pneumocystis following a primary acquired infection. Lung infection was apparently controlled by the immune response since fungal burdens decreased to become undetectable as specific antibodies reached high titres in serum. This immune response was apparently protective against reinfection 3 months later. 相似文献
64.
Ellen L. de Hollander Rik P. Bogers Hendriek C. Boshuizen Annika Rosengren Martin J. Shipley Paul Knekt Pierre Ducimetière Alessandro Menotti Lisette CPGM de Groot Wanda J.E. Bemelmans for the BMI‐CHD collaboration investigators 《Obesity (Silver Spring, Md.)》2013,21(5):865-880
Objective:
The association between obesity and coronary heart disease (CHD) may have changed over time, for example due to improved pharmacological treatment of CHD risk factors. This meta‐analysis of 31 prospective cohort studies explores the influence of calendar period on CHD risk associated with body mass index (BMI).Design and Methods:
The relative risks (RRs) of CHD for a five‐BMI‐unit increment and BMI categories were pooled by means of random effects models. Meta‐regression analysis was used to examine the influence of calendar period (>1985 v ≤1985) in univariate and multivariate analyses (including mean population age as a covariate).Results:
The age, sex, and smoking adjusted RR (95% confidence intervals) of CHD for a five‐BMI‐unit increment was 1.28(1.22:1.34). For underweight, overweight and obesity, the RRs (compared to normal weight) were 1.11(0.91:1.36), 1.31(1.22:1.41), and 1.78(1.55:2.04), respectively. The univariate analysis indicated 31% (95%CI: ?56:0) lower RR of CHD associated with a five‐BMI‐unit increment and a 51% (95%CI: ?78: ?14)) lower RR associated with obesity in studies starting after 1985 (n = 15 and 10, respectively) compared to studies starting in or before 1985 (n = 16 and 10). However, in the multivariate analysis, only mean population age was independently associated with the RRs for a five‐BMI‐unit increment and obesity (?29(95%CI: ?55: ?5)) and ?31(95%CI: ?66:3), respectively) per 10‐year increment in mean age).Conclusion:
This study provides no consistent evidence for a difference in the association between BMI and CHD by calendar period. The mean population age seems to be the most important factor that modifies the association between the risk of CHD and BMI, in which the RR decreases with increasing age.65.
N Doti C Reuther P L Scognamiglio A M Dolga N Plesnila M Ruvo C Culmsee 《Cell death & disease》2014,5(1):e993
Delayed neuronal cell death largely contributes to the progressive infarct development and associated functional impairments after cerebral ischemia or brain trauma. Previous studies exposed a key role for the interaction of the mitochondrial protein apoptosis-inducing factor (AIF) and cytosolic cyclophilin A (CypA) in pathways of programmed cell death in neurons in vitro and in vivo. These studies suggested that pro-apoptotic activities of AIF, such as its translocation to the nucleus and subsequent DNA degradation, depend on the physical interaction of AIF with CypA. Hence, this protein complex may represent a new pharmacological target for inhibiting the lethal action of AIF on the brain tissue. In this study, we show that the AIF amino-acid residues 370–394 mediate the protein complex formation of AIF with CypA. The synthetic AIF(370–394) peptide inhibited AIF/CypA complex formation in vitro by binding CypA with a KD of 12 μM. Further, the peptide exerted pronounced neuroprotective effects in a model of glutamate-induced oxidative stress in cultured HT-22 cells. In this model system of AIF-dependent cell death, the AIF(370–394) peptide preserved mitochondrial integrity, as detected by measurements of the mitochondrial membrane potential and quantification of mitochondrial fragmentation. Further, the AIF(370–394) peptide inhibited perinuclear accumulation of fragmented mitochondria, mitochondrial release of AIF to the nucleus and glutamate-induced cell death to a similar extent as CypA-siRNA. These data indicate that the targeting of the AIF-CypA axis is an effective strategy of neuroprotection. 相似文献
66.
Andrea Caporale Cristina Bolzati Giuseppina Maria Incisivo Nicola Salvarese Paolo Grieco Menotti Ruvo 《Journal of peptide science》2019,25(2)
In the field of angiogenesis, small cyclic pentapeptides containing the RGD motif are playing a relevant role for their high affinity and specificity for integrin receptors and for the possibility to act at both therapeutic and diagnostic level by inhibiting pathological angiogenesis and by serving as shuttles to deliver imaging‐probe including SPECT/PET radionuclides to specific tissues. In the last decade, several new protocols were reported in literature for the direct synthesis of cyclic RDG either in solution or by SPPS. Here, we have elaborated and tested some alternative approaches using different resins and different protective groups. The introduction of the dithiocarbamate function, useful to complex radio‐metals suitable for nuclear medicine applications, has also been considered and achieved. 相似文献
67.
Canassa-DeLeo Thais Campo Vanessa Leiria Rodrigues Lílian Cataldi Marchiori Marcelo Fiori Fuzo Carlos Brigido Marcelo Macedo Sandomenico Annamaria Ruvo Menotti Maranhão Andrea Queiroz Dias-Baruffi Marcelo 《Glycoconjugate journal》2020,37(1):77-93
Glycoconjugate Journal - Dystroglycanopathies are diseases characterized by progressive muscular degeneration and impairment of patient’s quality of life. They are associated with altered... 相似文献
68.
Nyström K Le Gall-Reculé G Grassi P Abrantes J Ruvoën-Clouet N Le Moullac-Vaidye B Lopes AM Esteves PJ Strive T Marchandeau S Dell A Haslam SM Le Pendu J 《PLoS pathogens》2011,7(8):e1002188
Rabbit Hemorrhagic disease virus (RHDV), a calicivirus of the Lagovirus genus, and responsible for rabbit hemorrhagic disease (RHD), kills rabbits between 48 to 72 hours post infection with mortality rates as high as 50-90%. Caliciviruses, including noroviruses and RHDV, have been shown to bind histo-blood group antigens (HBGA) and human non-secretor individuals lacking ABH antigens in epithelia have been found to be resistant to norovirus infection. RHDV virus-like particles have previously been shown to bind the H type 2 and A antigens. In this study we present a comprehensive assessment of the strain-specific binding patterns of different RHDV isolates to HBGAs. We characterized the HBGA expression in the duodenum of wild and domestic rabbits by mass spectrometry and relative quantification of A, B and H type 2 expression. A detailed binding analysis of a range of RHDV strains, to synthetic sugars and human red blood cells, as well as to rabbit duodenum, a likely gastrointestinal site for viral entrance was performed. Enzymatic cleavage of HBGA epitopes confirmed binding specificity. Binding was observed to blood group B, A and H type 2 epitopes in a strain-dependent manner with slight differences in specificity for A, B or H epitopes allowing RHDV strains to preferentially recognize different subgroups of animals. Strains related to the earliest described RHDV outbreak were not able to bind A, whereas all other genotypes have acquired A binding. In an experimental infection study, rabbits lacking the correct HBGA ligands were resistant to lethal RHDV infection at low challenge doses. Similarly, survivors of outbreaks in wild populations showed increased frequency of weak binding phenotypes, indicating selection for host resistance depending on the strain circulating in the population. HBGAs thus act as attachment factors facilitating infection, while their polymorphism of expression could contribute to generate genetic resistance to RHDV at the population level. 相似文献
69.
Musicco C Capelli V Pesce V Timperio AM Calvani M Mosconi L Cantatore P Gadaleta MN 《Journal of Proteomics》2011,74(11):2536-2547
Oxidative stress has a central role in aging and in several age-linked diseases such as neurodegenerative diseases, diabetes and cancer. Mitochondria, as the main cellular source and target of reactive oxygen species (ROS) in aging, are recognized as very important players in the above reported diseases. Impaired mitochondrial oxidative phosphorylation has been reported in several aging tissues. Defective mitochondria are not only responsible of bioenergetically less efficient cells but also increase ROS production further contributing to tissues oxidative stress. Acetyl-L-carnitine (ALCAR) is a biomolecule able to limit age-linked mitochondrial decay in brain, liver, heart and skeletal muscles by increasing mitochondrial efficiency. Here the global changes induced by aging and by ALCAR supplementation to old rat on the mitochondrial proteome of rat liver has been analyzed by means of the two-dimensional polyacrylamide gel electrophoresis. Mass spectrometry has been used to identify the differentially expressed proteins. A significant age-related change occurred in 31 proteins involved in several metabolisms. ALCAR supplementation altered the levels of 26 proteins. In particular, ALCAR reversed the age-related alterations of 10 mitochondrial proteins relative to mitochondrial cristae morphology, to the oxidative phosphorylation and antioxidant systems, to urea cycle, to purine biosynthesis. 相似文献
70.
Audfray A Claudinon J Abounit S Ruvoën-Clouet N Larson G Smith DF Wimmerová M Le Pendu J Römer W Varrot A Imberty A 《The Journal of biological chemistry》2012,287(6):4335-4347
Burkholderia ambifaria is generally associated with the rhizosphere of plants where it has biocontrol effects on other microorganisms. It is also a member of the Burkholderia cepacia complex, a group of closely related bacteria that cause lung infections in immunocompromised patients as well as in patients with granulomatous disease or cystic fibrosis. Our previous work indicated that fucose on human epithelia is a frequent target for lectins and adhesins of lung pathogens (Sulák, O., Cioci, G., Lameignère, E., Balloy, V., Round, A., Gutsche, I., Malinovská, L., Chignard, M., Kosma, P., Aubert, D. F., Marolda, C. L., Valvano, M. A., Wimmerová, M., and Imberty, A. (2011) PLoS Pathog. 7, e1002238). Analysis of the B. ambifaria genome identified BambL as a putative fucose-binding lectin. The 87-amino acid protein was produced recombinantly and demonstrated to bind to fucosylated oligosaccharides with a preference for αFuc1-2Gal epitopes. Crystal structures revealed that it associates as a trimer with two fucose-binding sites per monomer. The overall fold is a six-bladed β-propeller formed by oligomerization as in the Ralstonia solanacearum lectin and not by sequential domains like the fungal fucose lectin from Aleuria aurantia. The affinity of BambL for small fucosylated glycans is very high as demonstrated by microcalorimetry (K(D) < 1 μM). Plant cell wall oligosaccharides and human histo-blood group oligosaccharides H-type 2 and Lewis Y are bound with equivalent efficiency. Binding to artificial glycosphingolipid-containing vesicles, human saliva, and lung tissues confirmed that BambL could recognize a wide spectrum of fucosylated epitopes, albeit with a lower affinity for biological material from nonsecretor individuals. 相似文献