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1.
Altered proteolysis of amyloid precursor protein is an important determinant of pathology development in Alzheimer''s disease. Here, we describe the detection of two novel fragments of amyloid precursor protein in H4 neuroglioma cells undergoing apoptosis. Immunoreactivity of these 25–35 kDa fragments to two different amyloid precursor protein antibodies suggests that they contain the amyloid-β region and an epitope near the C-terminus of amyloid precursor protein. Generation of these fragments is associated with cleavage of caspase-3 and caspase-7, suggesting activation of these caspases. Studies in neurons undergoing DNA damage-induced apoptosis also showed similar results. Inclusion of caspase inhibitors prevented the generation of these novel fragments, suggesting that they are generated by a caspase-dependent mechanism. Molecular weight prediction and immunoreactivity of the fragments generated suggested that such fragments could not be generated by cleavage at any previously identified caspase, secretase, or calpain site on amyloid precursor protein. Bioinformatic analysis of the amino acid sequence of amyloid precursor protein revealed that fragments fitting the observed size and immunoreactivity could be generated by either cleavage at a novel, hitherto unidentified, caspase site or at a previously identified matrix metalloproteinase site in the extracellular domain. Proteolytic cleavage at any of these sites leads to a decrease in the generation of α-secretase cleaved secreted APP, which has both anti-apoptotic and neuroprotective properties, and thus may contribute to neurodegeneration in Alzheimer''s disease. 相似文献
2.
Dario Tavazzi Franco Martinez di Montemuros Silvia Fargion Anna Ludovica Fracanzani Gemino Fiorelli Maria Domenica Cappellini 《Cellular and molecular biology, including cyto-enzymology》2002,48(1):27-32
Porphyria cutanea tarda (PCT) is a human metabolic disorder due to the acquired or genetic impairment of uroporphyrinogen decarboxylase (URO-D) activity, the fifth enzyme of the heme biosynthetic pathway. A classification of inherited and non-inherited forms is based on the enzyme activity levels in red blood cells (RBC). Clinical manifestations of PCT are often precipitated by triggering factors such as alcohol, drug abuse, estrogens, virus infections, hepatotoxic chemicals and hepatic siderosis. We measured URO-D activity in RBC from a large sample of Italian PCT patients in order to define the enzyme activity distribution and to attempt a correlation among activity, risk factors and clinical outcome. Three classes of patients with low, normal and over-normal URO-D activity were defined according to control values. Low URO-D levels were present in 25.8% of patients, suggesting the familial form of PCT (type II). In this group, the outcome of PCT seems to be less influenced by risk factors. Patients with over-normal URO-D activity in RBC deserve further investigation. 相似文献
3.
4.
Gouttenoire L Fiorelli JL Trommenschlager JM Coquil X Cournut S 《Animal : an international journal of animal bioscience》2010,4(6):827-841
Reproductive performance has recently been a growing concern in cattle dairy systems, but few research methodologies are available to address it as a complex problem in a livestock farming system. The aim of this paper is to propose a methodology that combines both systemic and analytical approaches in order to better understand and improve reproductive performance in a cattle dairy system. The first phase of our methodology consists in a systemic approach to build the terms of the problem. It results in formalising a set of potential risk factors relevant for the particular system under consideration. The second phase is based on an analytical approach that involves both analysing the shapes of the individual lactation curves and carrying out logistic regression procedures to study the links between reproductive performance and the previously identified potential risk factors. It makes it possible to formulate hypotheses about the biotechnical phenomena underpinning reproductive performance. The last phase is another systemic approach that aims at suggesting new practices to improve the situation. It pays particular attention to the consistency of those suggestions with the farmer's general objectives. This methodology was applied to a French system experiment based on an organic low-input grazing system. It finally suggested to slightly modify the dates of the breeding period so as to improve reproductive performance. The formulated hypotheses leading to this suggestion involved both the breed (Holstein or Montbéliarde cows), the parity, the year and the calving date with regard to the turnout date as the identified risk factors of impaired performance. Possible use of such a methodology in any commercial farm encountering a biotechnical problem is discussed. 相似文献
5.
Effects of cytokines from activated immune cells on vascular cell growth and HIV-1 gene expression. Implications for AIDS-Kaposi's sarcoma pathogenesis. 总被引:10,自引:0,他引:10
G Barillari L Buonaguro V Fiorelli J Hoffman F Michaels R C Gallo B Ensoli 《Journal of immunology (Baltimore, Md. : 1950)》1992,149(11):3727-3734
Kaposi's sarcoma (KS) arises more frequently in homosexual and bisexual men than in other groups of HIV-1 infected individuals. Clinico-epidemiologic data indicate that homosexuals often are infected with multiple microbial agents and/or subjected to other antigenic stimuli, preceding or accompanying HIV-1 infection. Signs of immune activation, in fact, frequently have been detected in these individuals, and the onset of KS can precede any sign of immunodeficiency. These data have suggested that products from activated immune cells may affect the development of AIDS-KS. Here we report that conditioned media from activated or dysregulated T cells contain a variety of cytokines that promote the growth of spindle cells derived from KS lesions of AIDS patients (AIDS-KS cells) and induce normal vascular cells, potential cell progenitors of the AIDS-KS cells, to acquire features of the KS cell phenotype ("spindle" cell morphology and growth responsiveness to the mitogenic effect of extracellular HIV-1 Tat protein). The same conditioned media or cytokines promote HIV-1 gene expression and rescue defective HIV-1 proviruses, interrupting HIV-1 latency and increasing Tat production. The cellular and viral effects of cytokines are increased in an additive or synergistic manner by picomolar concentrations of extracellular Tat. These data suggest that cytokines produced by activated immune cells cooperate with HIV-1 infection in AIDS-KS pathogenesis. 相似文献
6.
A gene controlling fetal hemoglobin expression in adults is not linked to the non-alpha globin cluster. 总被引:7,自引:2,他引:5 下载免费PDF全文
A M Gianni M Bregni M D Cappellini G Fiorelli R Taramelli B Giglioni P Comi S Ottolenghi 《The EMBO journal》1983,2(6):921-925
The possible linkage between a gene causing heterocellular hereditary persistence of fetal hemoglobin (HPFH) and human non-alpha globin loci has been studied in a large Sardinian family. In this family a homozygous beta o-thalassemic patient was found, with an unusually mild form of this disease, which was ascribed to the co-existence of a gene causing heterocellular HPFH. DNA polymorphisms in the non-alpha globin cluster were analyzed by restriction enzyme digestion with HincII, HindIII and BamHI and with epsilon-, gamma-and beta-globin probes; the pattern of inheritance of these polymorphisms indicates that the HPFH gene is transmitted with one beta o-thalassemic gene in a single instance, with the second beta o-thalassemic gene in three instances and with a normal beta-globin gene in two cases. These data indicate that this HPFH gene is not linked to the non-alpha globin gene cluster, in contrast to previous observations with different HPFH genes, and suggest that this gene might code for diffusible substances acting, directly or indirectly, on gamma-globin gene expression. 相似文献
7.
V S Hinshaw W J Bean R G Webster J E Rehg P Fiorelli G Early J R Geraci D J St Aubin 《Journal of virology》1984,51(3):863-865
Influenza A virus isolates of the H4N5 subtype (which has previously been detected only in birds) were recovered from harbor seals dying of viral pneumonia on the New England coast from June 1982 through March 1983. When these isolates were compared with other mammalian and avian viruses in serological assays and RNA-RNA competitive hybridization, it was found that the seal viruses were most closely related antigenically and genetically to recent avian virus strains and were readily distinguishable from mammalian viruses, including H7N7 isolates recovered from seals in 1980. Unlike any previous isolates from mammals, these recent seal viruses replicate in the intestinal tracts of ducks, a characteristic of avian viruses. The association of avian viruses with influenza outbreaks in seals suggests that transmission of avian viruses to seals is occurring in nature. Potentially, this may be an example of the adaptation of avian viruses to mammals, which would represent an intermediate step in the evolution of new mammalian strains. 相似文献
8.
Zecchi-Orlandini S Formigli L Tani A Benvenuti S Fiorelli G Papucci L Capaccioli S Orlandini GE Brandi ML 《Biochemical and biophysical research communications》1999,255(3):680-685
Although compelling data have demonstrated the effectiveness of estrogen replacement therapy for the treatment of accelerated bone loss in postmenopausal osteoporosis and ovariectomized animals, the mechanisms by which estrogens reduce bone resorption remain to be elucidated. To address this issue, in the present study we investigated whether estrogens were able to induce programmed cell death or apoptosis in osteoclast precursors. To this purpose, a preosteoclastic cell line (FLG 29.1) was cultured in the absence or presence of nanomolar concentrations of 17beta-estradiol (17betaE2). Using time-lapse videomicroscopy, it was shown that 17betaE2 induced FLG 29.1 cell apoptosis in a dose- and time-dependent manner. Furthermore, a significant increase in the activity of caspase 3 enzyme and in the number of nuclei undergoing DNA fragmentation was observed in FLG 29.1 cells treated with 17betaE2 compared to untreated cells. Finally, transmission electron microscopy of the treated cells showed typical apoptotic morphology. These data indicate that 17betaE2 is able to promote in vitro apoptosis in preosteoclastic cells and suggest that estrogenic molecules may exert in vivo a direct role in negatively modulating the pool of undifferentiated bone marrow cells capable ultimately of maturing into osteoclasts. 相似文献
9.
G. Fiorelli F. Gori L. Masi U. Frediani M. L. Brandi A. Tanini P. A. Bernabei R. T. Ballock L. M. Wakefield M. B. Sporn 《Journal of cellular physiology》1994,160(3):482-490
Increasing evidence suggests that transforming growth factor-β (TGF-β) is involved in bone formation during remodeling. Using a recently cloned human leukemic cell line (FLG 29.1 cells) we demonstrate that these cells synthesize and secrete TGF-β1 and that exogenous or autocrine TGF-β1 can induce the same features of osteoclastic-like cells, exerting its effects through the binding to TGF-β specific receptors. Scatchard analysis of 125I-labeled TGF-β1 to FLG 29.1 cells revealed the presence of a single high affinity binding site with a Kd value of ~25 pM and a binding capacity of ~900 sites/cell. Affinity labeling experiments showed that FLG 29.1 cells express type I and type II TGF-β receptors. Stimulation of FLG 29.1 cells with low TGF-β1 doses reduced cell proliferation and increased cell adhesion and tartrate resistant acid phosphatase (TRAcP) activity. Pretreatment of FLG 29.1 cells with TGF-β1 caused a significant and dose-dependent response to calcitonin. Northern blot of total mRNA and analysis of the conditioned media (CM) showed that TGF-β1 was synthesized by FLG 29.1 cells. TPA treatment, which induces partial differentiation of these cells, markedly increased TGF-β1 mRNA expression and growth factor release. The majority of TGF-β1 secreted by TPA-treated cells was in its latent form. However, anti-TGF-β antibodies inhibited TGF-β1 and TPA-induced growth inhibition, calcitonin responsiveness, and TRAcP activity, suggesting that the TPA effect is mediated in part by autocrine TGF-β1 and indicating that the cells can activate and respond to the TGF-β that they secrete. These findings support a potential autocrine role for TGF-β1 in osteoclast differentiation. © 1994 Wiley-Liss, Inc. 相似文献
10.
Luciana Gabriel Nogueira Ronaldo Honorato Barros Santos Barbara Maria Ianni Alfredo Inácio Fiorelli Eliane Conti Mairena Luiz Alberto Benvenuti Amanda Frade Eduardo Donadi Fabrício Dias Bruno Saba Hui-Tzu Lin Wang Abilio Fragata Marcelo Sampaio Mario Hiroyuki Hirata Paula Buck Charles Mady Edimar Alcides Bocchi Noedir Antonio Stolf Jorge Kalil Edecio Cunha-Neto 《PLoS neglected tropical diseases》2012,6(10)