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1.
CFTR was reported to regulate ENaC channel opening, decreasing ENaC activity in airways and increasing it in sweat ducts. We generated MDCK-I cell lines stably expressing tagged alphabetagammaENaC+CFTR or ENaC alone, and developed an assay to quantify cell-surface half-life of ENaC. Surprisingly, we found that co-expressed CFTR stabilizes ENaC at the plasma membrane, suggesting that CFTR regulates ENaC stability, not just opening. 相似文献
2.
β2-glycoprotein-I (β2GPI) is a phospholipid-binding plasma protein that consists of five homologous domains. Domain V is distinguished from others by bearing a positively charged lysine cluster and hydrophobic extra C-terminal loop. β2GPI has been known as a natural anticoagulant regulator. β2GPI exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase, tenase, and factor XII activation. It also binds factor XI and inhibits its activation. On the other hand, β2GPI inhibits anticoagulant activity of activated protein C. According to the data from knockout mice, β2GPI may contribute to thrombin generation in vivo. Phospholipid-bound β2GPI is one of the major target antigens for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). Binding of pathogenic anti-β2GPI antibodies increases the affinity of β2GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on the cell surface. These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of β2GPI. Impaired fibrinolysis has been reported in patients with APS. Using a newly developed chromogenic assay, we demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions from APS patients. Addition of monoclonal anti-β2GPI antibodies with β2GPI also decreased fibrinolytic activity in this assay system. β2GPI is proteolytically cleaved by plasmin in domain V (nicked β2GPI) and becomes unable to bind to phospholipids, reducing antigenicity against antiphospholipid antibodies. This cleavage occurs in patients with increased fibrinolysis turnover. Nicked β2GPI binds to plasminogen and suppresses plasmin generation in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA). Thus, nicked β2GPI plays a role in the extrinsic fibrinolysis via a negative feedback pathway loop. 相似文献
3.
We investigated the effects of suppression of complement activation at C3 level and inhibition of C5a on acute synovitis in rats. Acute synovitis was induced in Wistar rats by intra-articular (i.a.) injection into one knee of 0.3 mg of MoAb 6D1 (anti-rat CD59 antibody). In the treatment groups, soluble CR1 (sCR1) or C5a receptor (C5aR) antagonist was administered intra-articularly or intravenously and effects on the course of the acute synovitis were monitored. Synovitis induced by 6D1 was characterized by joint swelling, thickening of synovial tissue, cellular infiltration and deposition of membrane attack complex (MAC) on the synovial surface. Neither inflammatory change nor MAC deposition was found in rats which received an i.a. injection of sCR1 to suppress complement activity in the joint. Intra-articular injection of sCR1 did not reduce plasma complement activity. Intravenous administration of sCR1 suppressed plasma complement activity but had no effect on the course of the arthritis and synovitis with MAC deposition was observed. Neither i.a. nor i.v. injection of C5aR antagonist had any suppressive effects on inflammatory change or MAC deposition in synovium. The data show that inflammatory change induced by 6D1 was mediated by local complement activation and was not accompanied by systemic complement activation. C5a generation was not responsible for the observed inflammation, suggesting that other complement activation products, possibly MAC, mediate the inflammatory change observed in this model of acute synovitis in rats. 相似文献
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We previously demonstrated susceptibility of Leishmania sp. to glibenclamide, a K+-ATP transport blocker which interacts with members of the superfamily of adenosine 5′ triphosphate-binding cassette transporters.
In order to characterize the molecular differences between a sensitive Leishmania strain, NR(Gs), and an experimentally selected glibenclamide-resistant strain, NR(Gr), specific biochemical and functional
parameters have been evaluated both in the wild type and in the resistant strain. Most noteworthy, NR(Gr) exhibit an increased
expression of P-glycoprotein and a decreased activity of functional key enzymes such as acid phosphatase, a prominent virulent
factor of the parasite, and pyruvate kinase, a key control enzyme for both carbohydrate and protein metabolism. The specific
biochemical, metabolic and functional changes observed in the resistant strain correlated with a reduced infectivity of stationary
phase NR(Gr) in J774 macrophages and suggested a mechanism to overcome the effect of glibenclamide.
Received: 21 January 2000 / Accepted: 1 March 2000 相似文献
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Bronchiolar expression of aquaporin-3 (AQP3) in rat lung and its dynamics in pulmonary oedema 总被引:5,自引:0,他引:5
Sato K Kobayashi K Aida S Tamai S 《Pflügers Archiv : European journal of physiology》2004,449(1):106-114
Aquaporins (AQPs) are water channel proteins that permit osmotically driven water movement. To determine their dynamics in pulmonary oedema, we examined the expression of mRNA and protein for AQP1, AQP3, AQP4, and AQP5 in the lungs of normal and thiourea-treated rats. In the thiourea group, lung water content increased significantly (vs. controls) with the peak at around 4 h. Semi-quantitative RT-PCR showed that AQP3 mRNA in the thiourea group rose significantly, peaking at around 4–8 h. The expression of AQP1, AQP4, AQP5, ENaC and CFTR mRNA each decreased significantly some time after the peak in lung water content. Immunoblot analysis showed that glycosylated AQP3 protein was increased 4–10 h after treatment. Expression of the other AQP proteins was not significantly altered, except for that of AQP4. Immunohistochemical examination revealed that AQP1 was expressed in endothelia, AQP3 in the basal cells of the large airways and in cuboidal cells in the bronchioles, AQP4 in the basolateral membrane of airway cells and AQP5 in type-I pneumocytes. Our results suggest that AQP3 is expressed not only in large airways, but also in bronchioles, and is related to water movement in pulmonary oedema. 相似文献
10.
Deepika D'Cunha Burkardt Anna Zachariou Chey Loveday Clare L. Allen David J. Amor Anna Ardissone Siddharth Banka Alexia Bourgois Christine Coubes Cheryl Cytrynbaum Laurence Faivre Gerard Marion Rachel Horton Dieter Kotzot Guillermo Lay‐Son Melissa Lees Karen Low Ho‐Ming Luk Paul Mark Allyn McConkie‐Rosell Marie McDonald John Pappas Christophe Phillipe Deborah Shears Brian Skotko Fiona Stewart Helen Stewart I Karen. Temple Frederic T. Mau‐Them Ricardo A. Verdugo Rosanna Weksberg Yuri A. Zarate John M. Graham Katrina Tatton‐Brown 《American journal of medical genetics. Part A》2019,179(10):2049-2055