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121.
Ferro ES Carreno FR Goni C Garrido PA Guimaraes AO Castro LM Oliveira V Araujo MC Rioli V Gomes MD Fontenele-Neto JD Hyslop S 《Protein and peptide letters》2004,11(5):415-421
Endopeptidase 24.15 (EC 3.4.24.15; EP24.15) and endopeptidase 24.16 (EC 3.4.24.16; EP24.16) are enzymes involved in general peptide metabolism in mammalian cells and tissues. This review will focus on morphological and biochemical aspects related to the subcellular distribution and secretion of these homologous enzymes in the central nervous system. These are important issues for a better understanding of the functions of EP24.15 and EP24.16 within neuroendocrine systems. 相似文献
122.
Frank Doyle Davida De La Harpe Hannah McGee Emer Shelley Ronán Conroy 《BMC cardiovascular disorders》2005,5(1):1-8
Background
Awareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need.Methods
Morbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations.Results
Half of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events.Conclusion
A diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased. 相似文献123.
Oliveira V Garrido PA Rodrigues CC Colquhoun A Castro LM Almeida PC Shida CS Juliano MA Juliano L Camargo AC Hyslop S Roberts JL Grum-Tokars V Glucksman MJ Ferro ES 《The FEBS journal》2005,272(12):2978-2992
The metalloendopeptidase 24.15 (EP24.15) is ubiquitously present in the extracellular environment as a secreted protein. Outside the cell, this enzyme degrades several neuropeptides containing from 5 to 17 amino acids (e.g. gonadotropin releasing hormone, bradykinin, opioids and neurotensin). The constitutive secretion of EP24.15 from glioma C6 cells was demonstrated to be stimulated linearly by reduced concentrations of extracellular calcium. In the present report we demonstrate that extracellular calcium concentration has no effect on the total amount of the extracellular (cell associated + medium) enzyme. Indeed, immuno-cytochemical analyses by confocal and electron microscopy suggested that the absence of calcium favors the enzyme shedding from the plasma membrane into the medium. Two putative calcium-binding sites on EP24.15 (D93 and D159) were altered by site-directed mutagenesis to investigate their possible contribution to binding of the enzyme at the cell surface. These mutated recombinant proteins behave similarly to the wild-type enzyme regarding enzymatic activity, secondary structure, calcium sensitivity and immunoreactivity. However, immunocytochemical analyses by confocal microscopy consistently show a reduced ability of the D93A mutant to associate with the plasma membrane of glioma C6 cells when compared with the wild-type enzyme. These data and the model of the enzyme's structure as determined by X-ray diffraction suggest that D93 is located at the enzyme surface and is consistent with membrane association of EP24.15. Moreover, calcium was also observed to induce a major change in the EP24.15 cleavage site on distinctive fluorogenic substrates. These data suggest that calcium may be an important modulator of ep24.15 cell function. 相似文献
124.
Differential expression of glycosaminoglycans and proteoglycans in the migratory pathway of the primordial germ cells of the mouse 总被引:3,自引:3,他引:0
Primordial germ cells are an embryonic cell line that give rise to gametes in vertebrates. They originate outside the embryo proper and migrate by a well-defined route to the genital ridges. Proteoglycans and glycosaminoglycans have distinctive properties that affect many of the characteristics of the extracellular microenvironment of migratory pathways in a variety of developmental systems. The purpose of this work was to identify the proteoglycans and glycosaminoglycans that are spatially and temporally expressed in the migratory pathway of primordial germ cells. We showed that the expression of proteoglycans and glycosaminoglycans in the primordial germ cells migratory pathway changes according to the different phases of the migratory process. Some molecules such as chondroitin-0-sulfate, decorin, and biglycan are present only in certain phases of the migratory process of primordial germ cells. Heparan sulfate, chondroitin-6-sulfate, versican, perlecan, and syndecan-4, although exhibiting some variation in expression were detected during all phases of the migratory process. Our results indicate that the successive steps of primordial germ cell migration require a coordinated expression of proteoglycans and glycosaminoglycans, that should be present in appropriate levels and in specific areas of the embryo, and that the sequential expression of these extracellular matrix molecules is under a genetic program that appears to be common to a variety of cell types during embryonic development. 相似文献
125.
This paper reviews the operation of a full-scale, fixed-bed digester treating a citric acid production wastewater with a COD: sulphate ratio of 3–4 : 1. Support matrix pieces were removed from the digester at intervals during the first 5 years of operation in order to quantify the vertical distribution of biomass within the digester. Detailed analysis of the digester biomass after 5 years of operation indicated that H2 and propionate-utilising SRB had outcompeted hydrogenophilic methanogens and propionate syntrophs. Acetoclastic methanogens were shown to play the dominant role in acetate conversion. Butyrate and ethanol-degrading syntrophs also remained active in the digester after 5 years of operation.Laboratory-scale hybrid reactor treatment at 55 °C of a diluted molasses influent, with and without sulphate supplementation, showed that the reactors could be operated with high stability at volumetric loading rates of 24 kgCOD.m-3.d-1 (12 h HRT). In the presence of sulphate (2 g/l-1; COD/sulphate ratio of 6 : 1), acetate conversion was severely inhibited, resulting in effluent acetate concentrations of up to 4000 mg.l-1. 相似文献
126.
A restriction map of the 272-kb IncHI2 plasmid R478 was constructed by using the enzymes ApaI, XbaI, SalI, and XhoI. The map was derived from cloned restriction fragments from R478 inserted into cosmid and plasmid vectors as well as from double-digestion analysis of R478 and R478 miniplasmids. All previously known resistance determinants were cloned from R478, and their positions were located on the restriction map. A region involved in incompatibility was cloned and mapped. The location of a previously unreported arsenite resistance gene was also determined. The genes encoding tellurite resistance, colicin B resistance, and phage inhibition were found to be associated with a 6.7-kb SalI fragment of R478. 相似文献
127.
A. D. Blest Sally Stowe Margrit Carter Emer O'Gara Anita Delaney 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1992,171(4):523-532
1. | The light-dependent demolition of rhabdoms induced by a protein phosphatase inhibitor, okadaic acid (OKA) in retinas of a crab (Leptograpsus variegatus) is examined to determine whether the effects of OKA merely amplify the endocytosis of normal phototransductive membrane turnover, or are distinct from it. |
2. | OKA-induced demolition by dawn retinas maintained in vitro is partially blocked by either of two protein kinase C inhibitors, staurosporine and H-7. It is similarly blocked by a Ca2+-channel blocking agent, diltiazem. |
3. | Large night rhabdoms illuminated at 40 lux for up to 20 min are reduced by pinocytosis which is not inhibited by either staurosporine or diltiazem, each in the absence of OKA. |
4. | Pinocytosis is not blocked by a high concentration of a specific tyrosine kinase inhibitor, genistein in absence of OKA. |
5. | It is inferred that (i) phosphorylations of rhabdomeral proteins drive light-dependent, OKA-induced endocytosis; (ii) phosphorylations (including that of rhodopsin) do not drive normal, light-dependent endocytosis; (iii) tyrosine phosphorylations of a notional, minor population of rhabdomeral proteins are unlikely to determine, normal, light-dependent endocytosis of phototransductive membrane; (iv) entry of Ca2+ into R1-7 photoreceptors via either light-dependent or other channels is necessary for events provoked by OKA, but irrelevant to normal light-dependent endocytosis. |
128.
Christos Spanos Elaina M. Maldonado Ciarán P. Fisher Petchpailin Leenutaphong Ernesto Oviedo-Orta David Windridge Francisco J. Salguero Alexandra Bermúdez-Fajardo Mark E. Weeks Caroline Evans Bernard M. Corfe Naila Rabbani Paul J. Thornalley Michael H. Miller Huan Wang John F. Dillon Alberto Quaglia Anil Dhawan Emer Fitzpatrick J. Bernadette Moore 《Proteome science》2018,16(1):4
Background
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients.Methods
Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE?/?) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients.Results
Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r?=?0.520, p <?0.0001).Conclusion
Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted.129.
Christos Spanos Elaina M. Maldonado Ciarán P. Fisher Petchpailin Leenutaphong Ernesto Oviedo-Orta David Windridge Francisco J. Salguero Alexandra Bermúdez-Fajardo Mark E. Weeks Caroline Evans Bernard M. Corfe Naila Rabbani Paul J. Thornalley Michael H. Miller Huan Wang John F. Dillon Alberto Quaglia Anil Dhawan Emer Fitzpatrick J. Bernadette Moore 《Proteome science》2018,16(1):13
130.