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排序方式: 共有327条查询结果,搜索用时 78 毫秒
51.
Katharina Flach Isabel Hilbrich Andrea Schiffmann Ulrich G?rtner Martin Krüger Marion Leonhardt Hanka Waschipky Lukas Wick Thomas Arendt Max Holzer 《The Journal of biological chemistry》2012,287(52):43223-43233
The microtubule-associated protein Tau is mainly expressed in neurons, where it binds and stabilizes microtubules. In Alzheimer disease and other tauopathies, Tau protein has a reduced affinity toward microtubules. As a consequence, Tau protein detaches from microtubules and eventually aggregates into β-sheet-containing filaments. The fibrillization of monomeric Tau to filaments is a multistep process that involves the formation of various aggregates, including spherical and protofibrillar oligomers. Previous concepts, primarily developed for Aβ and α-synuclein, propose these oligomeric intermediates as the primary cytotoxic species mediating their deleterious effects through membrane permeabilization. In the present study, we thus analyzed whether this concept can also be applied to Tau protein. To this end, viability and membrane integrity were assessed on SH-SY5Y neuroblastoma cells and artificial phospholipid vesicles, treated with Tau monomers, Tau aggregation intermediates, or Tau fibrils. Our findings suggest that oligomeric Tau aggregation intermediates are the most toxic compounds of Tau fibrillogenesis, which effectively decrease cell viability and increase phospholipid vesicle leakage. Our data integrate Tau protein into the class of amyloidogenic proteins and enforce the hypothesis of a common toxicity-mediating mechanism for amyloidogenic proteins. 相似文献
52.
冯婉娟徐子静孟令锋张蓉颖 《现代生物医学进展》2012,12(13):2582-2584
细胞内各个细胞器之间通过囊泡的膜转运是真核细胞存在的基本。Rab蛋白确保了转运蛋白被运输至正确的目的地。Rab蛋白是小GTP酶中的一大家族,它通过募集其效应物蛋白,其中包括接头蛋白,栓系因子,激酶,磷酸酶以及动力蛋白等,调控了细胞膜的选取,囊泡出芽,去包被,转运以及膜融合等过程。本文主要从Rab蛋白循环着手,依次论述了Rab蛋白在囊泡出芽,去包被,转运和膜融合等过程中起到的作用,从而使读者对Rab蛋白能有一个更加系统的了解。 相似文献
53.
Benno Sprey 《FEMS microbiology letters》1987,48(1-2):211-218
Abstract A cellulase-containing fraction present in the culture fluid of Trichoderma reesei grown on cellulose was obtained by fractionated centrifugation. The buoyant density of this fraction was D = 1.060 g/ml. Its ultrastructural properties, as detected by transmission electron microscopy, are given. The fraction consists of membrane vesicles attached to a carbohydrate polymer. This polymer is positive to Ruthenium red staining.
The effect of urea on the extraction and separation of acidic cellulases from this fraction is described. Linear gradient gels for both urea (up to 8.0 M urea) and polyacrylamide gels (up to 30%) were used to determine adequate separation conditions for isoelectric focusing (IEF) in a polyacrylamide gel matrix. The effect of urea on the extraction and separation conditions was tested by titration curves. In the presence of 6.0−8.0 M urea, the main cellulase-containing hydrolase complex (pIapp 4.2) from this fraction is split into 3 isoenzymes and a further cellulase (pI 5.65). 相似文献
The effect of urea on the extraction and separation of acidic cellulases from this fraction is described. Linear gradient gels for both urea (up to 8.0 M urea) and polyacrylamide gels (up to 30%) were used to determine adequate separation conditions for isoelectric focusing (IEF) in a polyacrylamide gel matrix. The effect of urea on the extraction and separation conditions was tested by titration curves. In the presence of 6.0−8.0 M urea, the main cellulase-containing hydrolase complex (pI
54.
We used water-soluble styryl pyridinium dyes that fluoresce at the membrane-water interface to study vesicle traffic in endothelial
cells. Cultured endothelial cells derived from bovine and human pulmonary microvessels were incubated in styryl probes, washed
to remove dye from the plasmalemmal outer face, and observed by digital fluorescence microscopy. Vesicles that derived from
plasmalemma by endocytosis were filled with the styryl dye. These vesicles were distributed throughout the cytosol as numerous
particles of heterogeneous diameter and brightness. Vesicle formation was activated 2-fold following addition of extracellular
albumin whereas a control protein, immunoglobulin G, had no effect. Dye uptake was abrogated by labeling at low temperatures
and inhibitors of phosphoinositide-3-kinase (PI 3-kinase). Tyrosine kinase inhibitors (genistein and herbimycin A) prevented
the albumin-induced vesicle formation. Cytochalasin B prevented vesicle redistribution indicating involvement of actin filaments
in translocation of endosomes away from sites of vesicle formation. Styryl dye was lost from cells by exocytosis as evident
by the disappearance of discrete fluorescent particles. N-ethylmaleimide and botulinum toxin types A and B caused cells to accumulate increased number of vesicles suggesting that exocytosis was regulated by NSF-dependent
SNARE mechanism. The results suggest that phosphoinositide metabolism regulates endocytosis in endothelial cells and that
extracellular albumin activates endocytosis by a mechanism involving tyrosine phosphorylation, whereas exocytosis is a distinct
process regulated by the SNARE machinery. The results support the hypothesis that albumin regulates its internalization and
release in vascular endothelial cells via activation of specific endocytic and exocytic pathways. 相似文献
55.
56.
Sergio Schenkman Pedro S. Araujo Ruud Dukman Frank H. Quina Hernan Chaimovich 《生物化学与生物物理学报:生物膜》1981,649(3):633-641
Small unilamellar vesicles of egg phosphatidylcholine (PC) or dimyristoylphosphatidylcholine, mixed with small unilamellar vesicles labelled with 2-(10-(1-pyrene)decanoyl)phosphatidylcholine, exhibit a constant average size and excimer to monomer (E/M) ratio for several hours when incubated at pH 3.6 at a temperature higher than the phase transition temperature (Tc) of the lipids. Addition of bovine serum albumin to this system produces a transient turbidity increase, a fast decrease in the E/M ratio, a partial loss of vesicle-entrapped [14C]sucrose and a measurable leak-in of externally added sucrose. Sepharose 4B filtration of the system demonstrates that the E/M ratio decrease is strictly paralleled by the formation of liposomes which exhibit a low E/M ratio and a hydrodynamic radius larger than that of small unilamellar vesicles. These data demonstrate that the E/M ratio decrease can be unequivocally ascribed to a vesicle-vesicle fusion process induced by serum albumin. The rate of serum-albumin induced fusion of small unilamellar vesicles is: (a) maximal at a stoichiometric ratio of approx. 2 albumins per vesicle: (b) sensitive to the nature of the lipid and; (c) not altered when human serum albumin replaces bovine serum albumin. The rate of albumin-induced fusion of dimyristoylphosphatidylcholine small unilamellar vesicles is higher below the Tc of the lipid and increases with temperature above the Tc. The formation of protein-bound aggregates with defined stoichiometries and a high local vesicle concentration, as well as changes in the local degree of hydration, are proposed to be the driving forces for the protein-induced vesicle fusion in this system. 相似文献
57.
A new type of device can prepare liposomes continuously, in large quantities and with excellent aqueous space capture efficiency. At initial lipid concentration of 300 μmol/ml these liposomes capture approx. 75% of cytosine arabinoside used as an aqueous space marker. Liposome size can be reduced by increasing the number of times the preparations are recycled through the microemulsifier. Liposomes less than 0.1 μm in diameter, as shown by electron microscopy, can be made easily. Liposomes prepared at 300 μmol/ml, composed of phosphatidylglycerol/phosphatidylcholine/cholesterol in a 0.1:0.4:0.5 molar ratio leaked less than 1% of entrapped cytosine arabinoside (Ara-C) at 4°C, and less than 10% Ara-C at 37°C plus serum, over a 48 h period. These liposomes could be useful for a number of applications including diagnostics, therapeutics and model membrane studies. 相似文献
58.
Hans-Günther Döbereiner Olaf Selchow Reinhard Lipowsky 《European biophysics journal : EBJ》1999,28(2):174-178
We present measurements of the effective spontaneous curvature of fluid lipid bilayers as a function of trans-bilayer asymmetry.
Experiments are performed on micrometer-scale vesicles in sugar solutions with varying species across the membrane. There
are two effects leading to a preferred curvature of such a vesicle. The spontaneous curvatures of the two monolayers as well
as their area difference combine into an effective spontaneous curvature of the membrane. Our technique for measuring this
parameter allows us to use vesicle morphology as a probe for general membrane-solute interactions affecting elasticity.
Received: 3 June 1998 / Revised version: 18 August 1998 / Accepted: 21 August 1998 相似文献
59.
A.V. Kuznetsov 《Mathematical biosciences》2010,226(2):147-155
The purpose of this paper is to develop a model for simulation of the formation of organelle traps in fast axonal transport. Such traps may form in the regions of microtubule polar mismatching. Depending on the orientation of microtubules pointing toward the trap region, these traps can accumulate either plus-end or minus-end oriented vesicles. The model predicts that the maximum concentrations of organelles occur at the boundaries of the trap regions; the overall concentration of organelles in the axon with traps is greatly increased compared to that in a healthy axon, which is expected to contribute to mechanical damages of the axon. The organelle traps induce hindrance to organelle transport down the axon; the total organelle flux down the axon with traps is found to be significantly reduced compared to that in a healthy axon. 相似文献
60.
《European journal of cell biology》2022,101(2):151219
Intermediary metabolism of tumors is characterized, in part, by a dysregulation of the cholesterol biosynthesis pathway at its rate-controlling enzyme providing the molecular basis for tumor membranes (mitochondria, plasma membrane) to become enriched with cholesterol (Bloch, 1965; Feo et al., 1975; Brown and Goldstein, 1980; Goldstein and Brown, 1990). Cholesterol enriched tumor mitochondria manifest preferential citrate export, thereby providing a continuous supply of substrate precursor for the tumor’s dysregulated cholesterogenesis via a “truncated” Krebs/TCA cycle (Kaplan et al., 1986; Coleman et al., 1997). Proliferating tumors shed elevated amounts of plasma membrane-derived extracellular vesicles (pmEV) compared with normal tissues (van Blitterswijk et al., 1979; Black, 1980). Coordination of these metabolic phenomena in tumors supports the enhanced intercalation of cholesterol within the plasma membrane lipid bilayer’s cytoplasmic face, the promotion of outward protrusions from the plasma membrane, and the evolution of cholesterol enriched pmEV. The pmEV shed by tumors possess elevated cholesterol and concentrated cell surface antigen clusters found on the tumor cells themselves (Kim et al., 2002). Upon exfoliation, saturation of the extracellular milieu with tumor-derived pmEV could allow early onset mammalian immune surveillance mechanisms to become “blind” to an evolving cancer and lose their ability to detect and initiate strategies to destroy the cancer. However, a molecular mechanism is lacking that would help explain how cholesterol enrichment of the pmEV inner lipid bilayer might allow the tumor cell to evade the host immune system. We offer a hypothesis, endorsed by published mathematical modeling of biomembrane structure as well as by decades of in vivo data with diverse cancers, that a cholesterol enriched inner bilayer leaflet, coupled with a logarithmic expansion in surface area of shed tumor pmEV load relative to its derivative cancer cell, conspire to force exposure of otherwise unfamiliar membrane integral protein domains as antigenic epitopes to the host’s circulating immune surveillance system, allowing the tumor cells to evade destruction. We provide elementary numerical estimations comparing the amount of pmEV shed from tumor versus normal cells. 相似文献