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51.
Marco?Barbariga Flavio?Curnis Annapaola?Andolfo Alan?Zanardi Massimo?Lazzaro Antonio?Conti Giuseppe?Magnani Maria?Antonietta?Volontè Laura?Ferrari Giancarlo?Comi Angelo?Corti Massimo?AlessioEmail author 《Molecular neurodegeneration》2015,10(1):59
Background
Ceruloplasmin, a ferroxidase present in cerebrospinal fluid (CSF), plays a role in iron homeostasis protecting tissues from oxidative damage. Its reduced enzymatic activity was reported in Parkinson’s disease (PD) contributing to the pathological iron accumulation. We previously showed that ceruloplasmin is modified by oxidation in vivo, and, in addition, in vitro by deamidation of specific NGR-motifs that foster the gain of integrin-binding function. Here we investigated whether the loss of ceruloplasmin ferroxidase activity in the CSF of PD patients was accompanied by NGR-motifs deamidation and gain of function.Results
We have found that endogenous ceruloplasmin in the CSF of PD patients showed structural changes, deamidation of the 962NGR-motif which is usually hidden within the ceruloplasmin structure, and the gain of integrin-binding function. These effects occur owing to the presence of abnormal levels of hydrogen peroxide we detected in the CSF of PD patients. Interestingly, the pathological CSF's environment of PD patients promoted the same modifications in the exogenously added ceruloplasmin, which in turn resulted in loss of ferroxidase-activity and acquisition of integrin-binding properties.Conclusions
We show that in pathological oxidative environment of PD-CSF the endogenous ceruloplasmin, in addition to loss-of-ferroxidase function, is modified as to gain integrin-binding function. These findings, beside the known role of ceruloplasmin in iron homeostasis, might have important pathogenic implications due to the potential triggering of signals mediated by the unusual integrin binding in cells of central nervous system. Furthermore, there are pharmacological implications because, based on data obtained in murine models, the administration of ceruloplasmin has been proposed as potential therapeutic treatment of PD, however, the observed CSF's pro-oxidant properties raise the possibility that in human the ceruloplasmin-based therapeutic approach might not be efficacious.52.
Drosophila melanogaster infected with Mycobacterium marinum suffer metabolic wasting similar to that seen in humans suffering from tuberculosis. This wasting is linked to insulin signaling and hastens host death. 相似文献
53.
Federico Lazzaro Michele Giannattasio Fabio Puddu Magda Granata Achille Pellicioli Paolo Plevani Marco Muzi-Falconi 《DNA Repair》2009,8(9):1055-1067
In response to genomic insults cells trigger a signal transduction pathway, known as DNA damage checkpoint, whose role is to help the cell to cope with the damage by coordinating cell cycle progression, DNA replication and DNA repair mechanisms. Accumulating evidence suggests that activation of the first checkpoint kinase in the cascade is not due to the lesion itself, but it requires recognition and initial processing of the lesion by a specific repair mechanism. Repair enzymes likely convert a variety of physically and chemically different lesions to a unique common structure, a ssDNA region, which is the checkpoint triggering signal. Checkpoint kinases can modify the activity of repair mechanisms, allowing for efficient repair, on one side, and modulating the generation of the ssDNA signal, on the other. This strategy may be important to allow the most effective repair and a prompt recovery from the damage condition. Interestingly, at least in some cases, if the damage level is low enough the cell can deal with the lesions and it does not need to activate the checkpoint response. On the other hand if damage level is high or if the lesions are not rapidly repairable, checkpoint mechanisms become important for cell survival and preservation of genome integrity. 相似文献
54.
Sarah M. Short Brian P. Lazzaro 《Proceedings. Biological sciences / The Royal Society》2010,277(1700):3649-3657
Post-mating reduction in immune defence is common in female insects, and a trade-off between mating and immunity could affect the evolution of immunity. In this work, we tested the capacity of virgin and mated female Drosophila melanogaster to defend against infection by four bacterial pathogens. We found that female D. melanogaster suffer post-mating immunosuppression in a pathogen-dependent manner. The effect of mating was seen after infection with two bacterial pathogens (Providencia rettgeri and Providencia alcalifaciens), though not after infection with two other bacteria (Enterococcus faecalis and Pseudomonas aeruginosa). We then asked whether the evolution of post-mating immunosuppression is primarily a ‘female’ or ‘male’ trait by assaying for genetic variation among females for the degree of post-mating immune suppression they experience and among males for the level of post-mating immunosuppression they elicit in their mates. We also assayed for an interaction between male and female genotypes to test the specific hypothesis that the evolution of a trade-off between mating and immune defence in females might be being driven by sexual conflict. We found that females, but not males, harbour significant genetic variation for post-mating immunosuppression, and we did not detect an interaction between female and male genotypes. We thus conclude that post-mating immune depression is predominantly a ‘female’ trait, and find no evidence that it is evolving under sexual conflict. 相似文献
55.
Wagner Vital Gustavo Lazzaro Rezende Leonardo Abreu Jorge Moraes Francisco JA Lemos Itabajara da Silva VazJr Carlos Logullo 《BMC developmental biology》2010,10(1):25
Background
The mosquito A. aegypti is vector of dengue and other viruses. New methods of vector control are needed and can be achieved by a better understanding of the life cycle of this insect. Embryogenesis is a part of A. aegypty life cycle that is poorly understood. In insects in general and in mosquitoes in particular energetic metabolism is well studied during oogenesis, when the oocyte exhibits fast growth, accumulating carbohydrates, lipids and proteins that will meet the regulatory and metabolic needs of the developing embryo. On the other hand, events related with energetic metabolism during A. aegypti embryogenesis are unknown. 相似文献56.
57.
Disruption of cellulose synthesis by isoxaben causes tip swelling and disorganizes cortical microtubules in elongating conifer pollen tubes 总被引:8,自引:0,他引:8
Summary. In elongating pollen tubes of the conifer Picea abies (Norway spruce), microtubules form a radial array beneath the plasma membrane only at the elongating tip and an array parallel
with elongation throughout the tube. Tips specifically swell following microtubule disruption. Here we test whether these
radial microtubules coordinate cell wall deposition and maintain tip integrity as tubes elongate. Control pollen tubes contain
cellulose throughout the walls, including the tip. Pollen tubes grown in the presence of isoxaben, which disrupts cellulose
synthesis, are significantly shorter with a decrease in cellulose throughout the walls. Isoxaben also significantly increases
the frequency of tip swelling, with no effect on tube width outside of the swollen tip. The decrease in cellulose is more
pronounced in pollen tubes with swollen tips. The effects of isoxaben are reversible. Following isoxaben treatment, the radial
array of microtubules persists beneath the plasma membrane of nonswollen tips, while this array is specifically disrupted
in swollen tips. Microtubules instead form a random network throughout the tip. Growth in these pollen tubes is turgor driven,
but the morphological changes due to isoxaben are not just the result of weakened cell walls since pollen tubes grown in hypoosmotic
media are not significantly shorter but do have swollen tips and tubes are wider along their entire length. We conclude that
the radial microtubules in the tip do maintain tip integrity and that the specific inhibition of cellulose microfibril deposition
leads to the disorganization of these microtubules. This supports the emerging model that there is bidirectional communication
across the plasma membrane between cortical microtubules and cellulose microfibrils.
Received January 15, 2002; accepted August 3, 2002; published online March 11, 2003 相似文献
58.
The spermatogenous body cell of the coniferPicea abies (Norway spruce) contains actin microfilaments
Mark D. Lazzaro 《Protoplasma》1998,201(3-4):194-201
Summary In conifer pollen, the generative cell divides into a sterile stalk cell and a body cell, which subsequently divides to produce two sperm. InPicea abies (Norway spruce, Pinaceae) this spermatogenous body cell contains actin microfilaments. Microfilament bundles follow the spherical contour of the body cell within the cell cortex, and also traverse the cytoplasm and enmesh amyloplasts and other organelles. In addition, microfilaments are associated with the surface of the body cell nucleus. The sterile stalk cell also contains microfilament bundles in the cytoplasm, around organelles, and along the nuclear surface. Within the pollen grain, microfilament bundles traverse the vegetative-cell cytoplasm and are enriched in a webbed cage which surrounds the body cell. Microfilaments were identified with rhodamine-phalloidin and with indirect immunofluo-rescence using a monoclonal antibody to actin. The majority of evidence in literature suggests that the spermatogenous generative cell in angiosperms does not contain actin microfilaments, so the presence of microfilaments within the spermatogenous body cell inP. abies appears to be a fundamental difference in sexual reproduction between conifers and angiosperms. 相似文献
59.
60.
The herpes simplex virus UL20 protein compensates for the differential disruption of exocytosis of virions and viral membrane glycoproteins associated with fragmentation of the Golgi apparatus. 总被引:8,自引:8,他引:0
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E Avitabile P L Ward C Di Lazzaro M R Torrisi B Roizman G Campadelli-Fiume 《Journal of virology》1994,68(11):7397-7405
The Golgi apparatus is fragmented and dispersed in Vero cells but not in human 143TK- cells infected with wild-type herpes simplex virus 1. Moreover, a recombinant virus lacking the gene encoding the membrane protein UL20 (UL20- virus) accumulates in the space between the inner and outer nuclear membranes of Vero cells but is exported and spreads from cell to cell in 143TK- cell cultures. Here we report that in Vero cells infected with UL20- virus, the virion envelope glycoproteins were of the immature type, whereas the viral glycoproteins associated with cell membranes were fully processed up to the addition of sialic acid, a trans-Golgi function. Moreover, the amounts of viral glycoproteins accumulating in the plasma membranes were considerably smaller than those detected on the surface of Vero cells infected with wild-type virus. In contrast, the amounts of viral glycoproteins present on the plasma membranes of 143TK- cells infected with wild-type or UL20- virus were nearly identical. We conclude that (i) in Vero cells infected with UL20- virus the block in the export of virions is at the entry into the exocytic pathway, and a second block in the exocytosis of viral glycoproteins associated with cytoplasmic membranes is due to an impairment of transport beyond Golgi fragments containing trans-Golgi enzymes and not to a failure of the Golgi oligosaccharide-processing functions; (ii) these defects are manifested in cells in which the Golgi apparatus is fragmented; and (iii) the UL20 protein compensates for these defects by enabling transport to and from the fragmented Golgi apparatus. 相似文献