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Albumin Transport

The Experts below are selected from a list of 219 Experts worldwide ranked by ideXlab platform

Alain Tedgui – 1st expert on this subject based on the ideXlab platform

  • Albumin Transport characteristics of rat aorta in early phase of hypertension
    Circulation Research, 1992
    Co-Authors: Alain Tedgui, Regine Merval, Bruno Esposito

    Abstract:

    The effects of early-stage hypertension on the macromolecular Transport characteristics of the aorta have been investigated in rats 1 week after the ligature of the abdominal aorta between the two renal arteries. The animals were left untreated or treated for 1 week with an angiotensin converting enzyme inhibitor (enalapril, 6 mg/kg per day). Blood pressure of a subgroup of hypertensive rats was acutely lowered to a normal level by injection of enalaprilat (1.5 mg/kg) at the time of the experiment. 131I-Albumin and 125I-Albumin were injected 90 minutes and 5 minutes, respectively, before the rats were killed. The transmural distribution of the relative tissue concentrations across the wall was obtained using a serial frozen-section technique. Short-term Albumin uptake permitted calculation of apparent endothelial permeability coefficients, and 90-minute uptake was used to estimate the steady-state Albumin distribution within the media. The effect of early-stage hypertension on the characteristics of the arterial macromolecular Transport depended on the aortic site; the ascending aortic arch appeared not to be affected. In the thoracic and abdominal aorta, the endothelial permeability coefficients increased significantly in hypertensive rats. This increase was not a direct effect of the arterial pressure, since the values were not significantly different when the pressure was acutely normalized. The 90-minute Albumin concentration in the media was enhanced in hypertensive rats and returned to the normal value by acutely lowering the blood pressure, indicating that the increase observed in hypertensive rats resulted from a direct effect of pressure, possibly increased pressure-driven convection and/or pressure-induced stretching of the wall. Treatment by angiotensin converting enzyme inhibitor prevented hypertension and protected against its effects in hypertensive animals.

  • Effect of the Transmural Pressure on LDL and Albumin Transport and Distribution Across the Intact Arterial Wall
    Biofluid Mechanics, 1990
    Co-Authors: Patrick A. Curmi, L Juan, Alain Tedgui

    Abstract:

    Recent progress in biology of the arterial wall have given a framework to account for the formation of atherosclerotic lesions. In particular, foam cells appear to be the result of low density lipoprotein (LDL) oxidation and of its uptake by the scavenger receptor of monocytes-macrophages that have migrated into the intima [1]. However, early plasma LDL accumulation in the subendothelial space seems to be required to trigger this process. In this respect, Transport of macromolecules may play a major role in atherogenesis. As with most of the plasma macromolecules, LDL pass through the vascular endothelium and are then Transported by diffusion/convection across the media [2].

  • effect of transmural pressure on low density lipoprotein and Albumin Transport and distribution across the intact arterial wall
    Circulation Research, 1990
    Co-Authors: Patrick A. Curmi, L Juan, Alain Tedgui

    Abstract:

    To investigate the effect of hyperpressure on the Transport of low density lipoprotein (LDL) and Albumin in the arterial wall, we measured in vitro the uptake of both iodine-131-labeled LDL and iodine-125-labeled Albumin in intact rabbit thoracic aorta, held at in vivo length and pressurized to 70 or 160 mm Hg. Arteries were incubated for 2 hours (n = 8) at 70 mm Hg, and for 5 minutes (n = 4), 30 minutes (n = 4), 1 hour (n = 5), and 2 hours (n = 5) at 160 mm Hg. The transmural distribution of the relative concentrations of LDL (CLDL) and Albumin (Calb) across the wall was determined by using a serial frozen sectioning technique. At 70 mm Hg, the mean medial CLDL and Calb values were 0.0018 +/- 0.0007 and 0.0039 +/- 0.0013, respectively. At 160 mm Hg, CLDL and Calb were markedly increased. The distribution of labeled Albumin was almost uniform across the media and reached a steady state after 30 minutes, whereas labeled LDL accumulated in the first inner layers, a steady state being achieved after 1 hour. The 1-hour values of CLDL in the first and second luminal sections (0.24 +/- 0.03 and 0.13 +/- 0.05, respectively) were much higher than those of Calb, the CLDL/Calb ratios being 4.12 +/- 0.94 and 2.34 +/- 0.42 (p less than 0.01), respectively. In the subsequent sections, the CLDL decreased markedly and became much lower than the Calb, the CLDL/Calb ratio averaging 0.2 in the two-thirds outer media. To investigate whether LDL was trapped at high pressure in the inner layers, vessels were exposed to a tracer-free intraluminal solution for 30 minutes, after a 30-minute incubation with tracers. After washout, Albumin was almost totally removed from the wall, while the CLDL were practically unchanged. Compaction of the media induced by high distending stresses applied to the vessel might have hindered the efflux of LDL, whereas Albumin moved freely through the wall. Synergy between increased endothelial permeability and compaction of the media together with enhanced pressure-driven convection might account for the marked increase in LDL concentration observed in the inner wall at high pressure.

A B Malik – 2nd expert on this subject based on the ideXlab platform

  • Role of Src-induced dynamin-2 phosphorylation in caveolae-mediated endocytosis in endothelial cells.
    Journal of Biological Chemistry, 2004
    Co-Authors: Ayesha N. Shajahan, A B Malik, C Tiruppathi, Barbara Timblin, Raudel Sandoval, Richard D. Minshall

    Abstract:

    Abstract Albumin transcytosis, a determinant of transendothelial permeability, is mediated by the release of caveolae from the plasma membrane. We addressed the role of Src phosphorylation of the GTPase dynamin-2 in the mechanism of caveolae release and Albumin Transport. Studies were made in microvascular endothelial cells in which the uptake of cholera toxin subunit B, a marker of caveolae, and 125I-Albumin was used to assess caveolae-mediated endocytosis. Albumin binding to the 60-kDa cell surface Albumin-binding protein, gp60, induced Src activation (phosphorylation on Tyr416) within 1 min and resulted in Src-dependent tyrosine phosphorylation of dynamin-2, which increased its association with caveolin-1, the caveolae scaffold protein. Expression of kinase-defective Src mutant interfered with the association between dynamin-2, which caveolin-1 and prevented the uptake of Albumin. Expression of non-Src-phosphorylatable dynamin (Y231F/Y597F) resulted in reduced association with caveolin-1, and in contrast to WT-dynamin-2, the mutant failed to translocate to the caveolin-rich membrane fraction. The Y231F/Y597F dynamin-2 mutant expression also resulted in impaired Albumin and cholera toxin subunit B uptake and reduced transendothelial Albumin Transport. Thus, Src-mediated phosphorylation of dynamin-2 is an essential requirement for scission of caveolae and the resultant transendothelial Transport of Albumin.

  • Evidence for the role of alveolar epithelial gp60 in active transalveolar Albumin Transport in the rat lung.
    The Journal of physiology, 2001
    Co-Authors: T A John, Richard D. Minshall, S M Vogel, K Ridge, C Tiruppathi, A B Malik

    Abstract:

    1. Transcytosis of Albumin, involving the 60 kDa Albumin-binding glycoprotein, gp60, was studied in cultured type II alveolar epithelial cells obtained from rat lungs. 2. Type II cells internalized the interfacial fluorescent dye RH 414, which marks for plasmalemma vesicles. Fluorescent forms of Albumin and anti-gp60 antibody colocalized in the same plasmalemma vesicles. 3. Antibody (100 microg ml(-1)) cross-linking of gp60 for brief periods (15 min) markedly stimulated vesicular uptake of fluorescently tagged Albumin. The caveolar disrupting agent, filipin (10 nM), abolished the stimulated internalization of Albumin. 4. The vast majority of plasmalemmal vesicles carrying Albumin also immunostained for caveolin-1; however, lysosomes did not stain for caveolin-1. Filipin depleted the epithelial cells of the caveolin-1-positive, AlbuminTransporting plasmalemma vesicles. 5. Prolonged (> 1 h) stimulation of type II cells with cross-linking anti-gp60 antibody produced loss of cell-surface gp60 and abolished endocytic Albumin uptake. 6. Transalveolar Transport of Albumin was also studied in the isogravimetric rat lung preparation perfused at 37 degrees C. (125)I-labelled Albumin was instilled into distal airspaces of lungs, and the resulting (125)I-labelled Albumin efflux into the vascular perfusate was determined. 7. Unlabelled Albumin (studied over a range of 0-10 g (100 instilled ml)(-1)) inhibited 40 % of the Transport of labelled Albumin ((5.7 +/- 0.4) x 10(5) counts (instilled ml)(-1)) with an IC(50) value of 0.34 g (100 ml)(-1). 8. Filipin blocked the displacement-sensitive component of (125)I-labelled Albumin Transport, but had no effect on the Transport of the paracellular tracer (3)[H]mannitol. 9. Displacement-sensitive (125)I-labelled Albumin Transport had a significantly greater Q(10) (27-37 degrees C) than the non-displaceable component. 10. Cross-linking of gp60 by antibody instillation stimulated only the displacement-sensitive (125)I-labelled Albumin transalveolar Transport in intact rat lungs. 11. To estimate the Transport capacity of the displacement-sensitive system, the percentage of instilled (125)I-labelled Albumin counts remaining in lung tissue was compared in lungs treated with instillates containing either 0.05 g (100 ml)(-1) unlabelled Albumin or 5 g (100 ml)(-1) unlabelled Albumin. Approximately 25 % of instilled (125)I-labelled Albumin was cleared from the lung preparations per hour by the displacement-sensitive Transport pathway. This component was blocked by filipin.

  • evidence for the role of alveolar epithelial gp60 in active transalveolar Albumin Transport in the rat lung
    The Journal of Physiology, 2001
    Co-Authors: T A John, Richard D. Minshall, S M Vogel, K Ridge, C Tiruppathi, A B Malik

    Abstract:

    The alveolar epithelium represents the rate-limiting barrier to solute and fluid Transport between the pulmonary capillary lumen and distal air spaces (Schneeberger & Karnovsky, 1971; Gorin et al. 1979; Berthiaume et al. 1989). The liquid in contact with the respiratory surface of alveoli is restricted to a thin layer of epithelial lining fluid (ELF). Type I alveolar epithelial cells regulate the ELF composition and volume, which in turn is important for the maintenance of low alveolar surface tension and efficient gas exchange. Relative to blood plasma, this fluid contains lower Na+ and higher K+ concentrations resulting from the activity of a Na+-K+ ionic pump in the basolateral epithelial membrane (Basset et al. 1987; Goodman et al. 1987; Valeyre et al. 1991; Rutschman et al. 1993; Saumon & Basset, 1993) and from passive Na+ Transport through apical Na+ channels (Matalon & O’Brodovich, 1999). The protein concentration in ELF is also found to be lower than that of plasma by a factor of 4 or more depending on the species investigated and methodology employed (Peterson et al. 1990; Peterson et al. 1993; Pusch et al. 1997). Such a steep protein concentration gradient implies the existence of an active Transport process for plasma proteins. In this regard, some investigators have recognized the existence of a monensin- and nocodazole-sensitive protein uptake pathway in alveolar epithelium of intact mammalian lungs (Hastings et al. 1994; Wangensteen et al. 1996); however, the quantitative importance of such uptake for overall alveolar protein clearance remains unclear (see review by Folkesson et al. 1996).

    Active Transport of protein molecules across endothelial cells was shown, in some instances, to occur by a receptor-mediated process (Vasile et al. 1983; Ghitescu et al. 1986; Descamps et al. 1996). In the pulmonary microvascular endothelium, Albumin bound with high specificity to the 60 kDa Albumin-binding glycoprotein (gp60 or albondin) and was shown to activate Albumin transcytosis through the endothelium (Schnitzer et al. 1988; Schnitzer, 1992; Tiruppathi et al. 1996; Minshall et al. 2000). Cross-linking of gp60 with an anti-gp60 antibody stimulated endocytosis (as measured by fluorescent styryl pyridinium probes) and Albumin uptake (quantified with radiolabelled Albumin) in cultured endothelial cells (Tiruppathi et al. 1997; Niles & Malik, 1999; Minshall et al. 2000). As a transcellular Albumin Transport pathway may also be present in alveolar epithelial cells (Kim et al. 1985), the purpose of the present study was to characterize the Albumin clearance mechanism of the alveolar epithelium with particular reference to the possible role of gp60 in regulating Albumin Transport in the intact lung.

Richard D. Minshall – 3rd expert on this subject based on the ideXlab platform

  • Regulation of transendothelial permeability by Src kinase.
    Microvascular Research, 2008
    Co-Authors: Guochang Hu, Richard D. Minshall

    Abstract:

    Abstract Transcellular Transport of Albumin from the endothelial lumen to the abluminal perivascular interstitium via caveolae is a primary determinant of basal endothelial permeability. Albumin binding to specific caveolae-associated proteins induces the internalization of caveolae from the endothelial plasma membrane. Albumin-containing caveolae detach from the plasma membrane and traffic to the opposite membrane where they release Albumin into the extravascular space. The events initiating transcytosis have been shown to be tightly regulated by Src family kinases, and thus Src signaling is thought to be a critical “switch” regulating caveolae-mediated transcellular Transport of the plasma protein Albumin. Recently, accumulating evidence indicates the importance of caveolae-mediated Albumin Transport in endothelial hyperpermeability in response to inflammatory stimuli. In this review, we focus on the current understanding of Src signaling in regulating basal permeability and inflammation-evoked increase in transcellular Albumin permeability of the pulmonary endothelium.

  • Role of Src-induced dynamin-2 phosphorylation in caveolae-mediated endocytosis in endothelial cells.
    Journal of Biological Chemistry, 2004
    Co-Authors: Ayesha N. Shajahan, A B Malik, C Tiruppathi, Barbara Timblin, Raudel Sandoval, Richard D. Minshall

    Abstract:

    Abstract Albumin transcytosis, a determinant of transendothelial permeability, is mediated by the release of caveolae from the plasma membrane. We addressed the role of Src phosphorylation of the GTPase dynamin-2 in the mechanism of caveolae release and Albumin Transport. Studies were made in microvascular endothelial cells in which the uptake of cholera toxin subunit B, a marker of caveolae, and 125I-Albumin was used to assess caveolae-mediated endocytosis. Albumin binding to the 60-kDa cell surface Albumin-binding protein, gp60, induced Src activation (phosphorylation on Tyr416) within 1 min and resulted in Src-dependent tyrosine phosphorylation of dynamin-2, which increased its association with caveolin-1, the caveolae scaffold protein. Expression of kinase-defective Src mutant interfered with the association between dynamin-2, which caveolin-1 and prevented the uptake of Albumin. Expression of non-Src-phosphorylatable dynamin (Y231F/Y597F) resulted in reduced association with caveolin-1, and in contrast to WT-dynamin-2, the mutant failed to translocate to the caveolin-rich membrane fraction. The Y231F/Y597F dynamin-2 mutant expression also resulted in impaired Albumin and cholera toxin subunit B uptake and reduced transendothelial Albumin Transport. Thus, Src-mediated phosphorylation of dynamin-2 is an essential requirement for scission of caveolae and the resultant transendothelial Transport of Albumin.

  • Evidence for the role of alveolar epithelial gp60 in active transalveolar Albumin Transport in the rat lung.
    The Journal of physiology, 2001
    Co-Authors: T A John, Richard D. Minshall, S M Vogel, K Ridge, C Tiruppathi, A B Malik

    Abstract:

    1. Transcytosis of Albumin, involving the 60 kDa Albumin-binding glycoprotein, gp60, was studied in cultured type II alveolar epithelial cells obtained from rat lungs. 2. Type II cells internalized the interfacial fluorescent dye RH 414, which marks for plasmalemma vesicles. Fluorescent forms of Albumin and anti-gp60 antibody colocalized in the same plasmalemma vesicles. 3. Antibody (100 microg ml(-1)) cross-linking of gp60 for brief periods (15 min) markedly stimulated vesicular uptake of fluorescently tagged Albumin. The caveolar disrupting agent, filipin (10 nM), abolished the stimulated internalization of Albumin. 4. The vast majority of plasmalemmal vesicles carrying Albumin also immunostained for caveolin-1; however, lysosomes did not stain for caveolin-1. Filipin depleted the epithelial cells of the caveolin-1-positive, AlbuminTransporting plasmalemma vesicles. 5. Prolonged (> 1 h) stimulation of type II cells with cross-linking anti-gp60 antibody produced loss of cell-surface gp60 and abolished endocytic Albumin uptake. 6. Transalveolar Transport of Albumin was also studied in the isogravimetric rat lung preparation perfused at 37 degrees C. (125)I-labelled Albumin was instilled into distal airspaces of lungs, and the resulting (125)I-labelled Albumin efflux into the vascular perfusate was determined. 7. Unlabelled Albumin (studied over a range of 0-10 g (100 instilled ml)(-1)) inhibited 40 % of the Transport of labelled Albumin ((5.7 +/- 0.4) x 10(5) counts (instilled ml)(-1)) with an IC(50) value of 0.34 g (100 ml)(-1). 8. Filipin blocked the displacement-sensitive component of (125)I-labelled Albumin Transport, but had no effect on the Transport of the paracellular tracer (3)[H]mannitol. 9. Displacement-sensitive (125)I-labelled Albumin Transport had a significantly greater Q(10) (27-37 degrees C) than the non-displaceable component. 10. Cross-linking of gp60 by antibody instillation stimulated only the displacement-sensitive (125)I-labelled Albumin transalveolar Transport in intact rat lungs. 11. To estimate the Transport capacity of the displacement-sensitive system, the percentage of instilled (125)I-labelled Albumin counts remaining in lung tissue was compared in lungs treated with instillates containing either 0.05 g (100 ml)(-1) unlabelled Albumin or 5 g (100 ml)(-1) unlabelled Albumin. Approximately 25 % of instilled (125)I-labelled Albumin was cleared from the lung preparations per hour by the displacement-sensitive Transport pathway. This component was blocked by filipin.