Search results for "DASE"
showing 10 items of 1891 documents
The crystal structure of a 250-kDa heterotetrameric particle explains inhibition of sheddase meprin β by endogenous fetuin-B
2021
Meprin β (Mβ) is a multidomain type-I membrane metallopeptidase that sheds membrane-anchored substrates, releasing their soluble forms. Fetuin-B (FB) is its only known endogenous protein inhibitor. Herein, we analyzed the interaction between the ectodomain of Mβ (MβΔC) and FB, which stabilizes the enzyme and inhibits it with subnanomolar affinity. The MβΔC:FB crystal structure reveals a ∼250-kDa, ∼160-Å polyglycosylated heterotetrameric particle with a remarkable glycan structure. Two FB moieties insert like wedges through a “CPDCP trunk” and two hairpins into the respective peptidase catalytic domains, blocking the catalytic zinc ions through an “aspartate switch” mechanism. Uniquely, the …
l-Carnitine l-tartrate supplementation favorably affects biochemical markers of recovery from physical exertion in middle-aged men and women.
2009
The purpose of this study was to examine the effects of Carnipure tartrate (Lonza, Allendale, NJ) supplementation (total dose of 2 g/d of l-carnitine) on markers of performance and recovery from physical exertion in middle-aged men and women. Normally active and healthy men (n = 9, 45.4 +/- 5.3 years old) and women (n = 9, 51.9 +/- 5.0 years old) volunteered to participate in the investigation. Double-blind, placebo, balanced treatment presentation and crossover design were used with 3 weeks and 3 days of supplementation followed by a 1-week washout period before the other counterbalanced treatment was initiated. After 3 weeks of each supplementation protocol, each participant then performe…
Transcriptome comparison of murine wild-type and synaptophysin-deficient retina reveals complete identity
2005
Loss of synaptophysin, one of the major synaptic vesicle membrane proteins, is surprisingly well tolerated in knockout mice. To test whether compensatory gene transcription accounts for the apparent lack of functional deficiencies, comparative transcriptome analyses were carried out. The retina was selected as the most suitable tissue since morphological alterations were observed in mutant photoreceptors, most notably a reduction of synaptic vesicles and concomitant increase in clathrin-coated vesicles. Labeled cRNA was prepared in triplicate from retinae of age- and sex-matched wild-type and mutant litter mates and hybridized to high-density microarray chips. Only three differentially expr…
Novel mutations of the ABCA12, KRT1 and ST14 genes in three unrelated newborns showing congenital ichthyosis.
2022
Abstract Background Congenital ichthyosis (CI) is a heterogeneous group of genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis, often associated to erythroderma. They are rare diseases, with overall incidence of 6.7 in 100,000. Clinical manifestations are due to mutations in genes mostly involved in skin barrier formation. Based on clinical presentation, CI is distinguished in non-syndromic and syndromic forms. To date, mutations of more than 50 genes have been associated to different types of CI. Cases presentation We report on three Italian unrelated newborns showing clinical signs compatible with different forms of CI of variable severity, namely Harlequin…
Frequency of Fabry disease in patients with small-fibre neuropathy of unknown aetiology: a pilot study
2010
Background: Early occurrence of small-fibre neuropathy (SFN) is a common feature of Fabry disease (FD) – an X-linked storage disorder caused by reduced activity of the α-galactosidase A (α-GAL). Although SFN may result from different disorders, the cause is often unclear. Therefore, we investigated the frequency of FD in patients with SFN of unknown aetiology. Methods: Patients with idiopathic SFN, established by sensory quantitative testing and/or skin biopsy, were examined for mutations in the α-GAL gene. Where mutations in the α-GAL gene were identified, levels of globotriaosylceramide (Gb3) were measured in urine and blood and the α-GAL activity was evaluated. When new mutations were …
Signal transduction pathways of membrane expression of proteinase 3 (PR‐3) in human endothelial cells
1997
At present, the exact mechanism of the pathogenic effect of anti-PR-3 antibodies remains unknown. Interaction of anti-neutrophil cytoplasmic antibodies (ANCAs) with human umbilical vein endothelial cells (HUVECs) may play a key role. Recently we were able to show that ANCAs recognize their target antigen, PR-3, translocated into the membrane of HUVECs. The objective of this study was to investigate regulation, i.e. signal transduction pathways, of PR-3 expression in endothelial cells. HUVECs were isolated according to the method of Jaffe et al. and cultured under standard conditions. A cyto-enzyme-linked immunosorbent assay (ELISA) with unfixed cells was performed. Membrane-expressed PR-3 w…
Human endothelial cells express proteinase 3, the target antigen of anticytoplasmic antibodies in Wegener's granulomatosis
1993
Abstract Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA), especially proteinase 3 (PR-3), have proved to be a useful clinical tool confirming the diagnosis or monitoring disease activity of Wegener's granulomatosis (WG). Although several concepts concerning the pathophysiologic potentials of ANCA have been discussed, only sparse data about ANCA-endothelium interactions have been available. In this study, we have investigated the expression of PR-3 in cytokine- treated human endothelial cells using purified anti-PR-3 antibodies of patients with WG, murine and human monoclonal anti-PR-3 antibodies as probes. We were able to show that tumor necrosis factor-alpha, int…
Antibodies to proteinase 3 mediate expression of vascular cell adhesion molecule-1 (VCAM-1).
1996
SUMMARY VCAM-1 was first identified as an adhesion molecule induced on human endothelial cells (HEC) by inflammatory cytokines such as IL-1, tumour necrosis factor (TNF), and lipopolysaccharide (LPS). The molecule binds to a variety of leucocytes, including B cells, T cells, basophils, eosinophils and monocytes. Vascular expression of VCAM-1 has been associated with a number of disease states, including rheumatoid arthritis and vasculitis. The detection of antineutrophil cytoplasmic antibodies (ANCA), especially to proteinase 3 (PR3), has become important in the diagnosis of Wegener’s granulomatosis (WG) and related vasculitides. Recently we were able to demonstrate a direct effect of anti-…
Inhibition of the myosin light chain kinase prevents hypoxia-induced blood-brain barrier disruption
2007
Increased mortality after stroke is associated with development of brain edema. The aim of the present study was to examine the contribution of endothelial myosin light chain (MLC) phosphorylation to hypoxia-induced blood-brain barrier (BBB) opening. Measurements of trans-endothelial electrical resistance (TEER) were performed to analyse BBB integrity in an in vitro co-culture model (bovine brain microvascular endothelial cells (BEC) and rat astrocytes). Brain fluid content was analysed in rats after stroke induction using a two-vein occlusion model. Dihydroethidium was used to monitor intracellular generation of reactive oxygen species (ROS) in BEC. MLC phosphorylation was detected using i…
β-Aminobutyric Acid Primes an NADPH Oxidase–Dependent Reactive Oxygen Species Production During Grapevine-Triggered Immunity
2010
International audience; The molecular mechanisms underlying the process of priming are poorly understood. In the present study, we investigated the early signaling events triggered by β-aminobutyric acid (BABA), a well-known priming-mediated plant resistance inducer. Our results indicate that, in contrast to oligogalacturonides (OG), BABA does not elicit typical defense-related early signaling events nor defense-gene expression in grapevine. However, in OG-elicited cells pretreated with BABA, production of reactive oxygen species (ROS) and expression of the respiratory-burst oxidase homolog RbohD gene were primed. In response to the causal agent of downy mildew Plasmopara viticola, a strong…