Temperature dependence of fluid phase endocytosis coincides with membrane properties of pig platelets

Wolkers, Willem F.; Looper, Sheri A.; Fontanilla, Ray A; Tsvetkova, Nelly M.; Tablin, Fern; Crowe, John H.

doi:10.1016/s0005-2736(03)00114-7

Cited by 62 publications

(49 citation statements)

References 37 publications

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“…Trehalose does not readily cross cell membranes, but can be efficiently loaded into mammalian cells via fluid-phase endocytosis and pinocytosis (3, 40) like other small molecules that do not readily cross membranes (41). Extracellular trehalose is likely acting in the cytosol in the same compartment(s) as the trehalose in the stable cells.…”

Section: Discussionmentioning

confidence: 99%

Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and α-Synuclein

Sarkar

Davies

Huang

et al. 2007

Journal of Biological Chemistry

1,017

881

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Trehalose, a disaccharide present in many non-mammalian species, protects cells against various environmental stresses. Whereas some of the protective effects may be explained by its chemical chaperone properties, its actions are largely unknown. Here we report a novel function of trehalose as an mTOR-independent autophagy activator. Trehalose-induced autophagy enhanced the clearance of autophagy substrates like mutant huntingtin and the A30P and A53T mutants of ␣-synuclein, associated with Huntington disease (HD) and Parkinson disease (PD), respectively. Furthermore, trehalose and mTOR inhibition by rapamycin together exerted an additive effect on the clearance of these aggregate-prone proteins because of increased autophagic activity. By inducing autophagy, we showed that trehalose also protects cells against subsequent pro-apoptotic insults via the mitochondrial pathway. The dual protective properties of trehalose (as an inducer of autophagy and chemical chaperone) and the combinatorial strategy with rapamycin may be relevant to the treatment of HD and related diseases, where the mutant proteins are autophagy substrates.Trehalose is a non-reducing disaccharide found in many organisms, including bacteria, yeast, fungi, insects, invertebrates, and plants. It is the natural hemolymph sugar of invertebrates. It functions to protect the integrity of cells against various environmental stresses like heat, cold, desiccation, dehydration, and oxidation by preventing protein denaturation (1). Many of the stress-protecting properties of trehalose were discovered in yeast (2); however, it also has beneficial effects in mammals where it is not endogenously synthesized. For instance, it may be a valuable tool for cryopreservation of cells (1, 3). It is not clear how trehalose mediates many of its protective effects, but some may be via its ability to act as chemical chaperone and influence protein folding through direct protein-trehalose interactions (4). Trehalose inhibits amyloid formation of insulin in vitro (5) and prevents aggregation of ␤-amyloid associated with Alzheimer disease (6). Recently, trehalose was shown to inhibit polyglutamine (polyQ) 3 -mediated protein aggregation in vitro, reduce mutant huntingtin aggregates and toxicity in cell models and alleviate polyQ-induced pathology in the R6/2 mouse model of Huntington disease (HD) (7). This protective effect was suggested to be caused by trehalose binding to expanded polyQ and stabilizing the partially unfolded mutant protein.HD is an autosomal-dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion, which results in an abnormally long polyQ tract in the N terminus of the huntingtin protein. Asymptomatic individuals have 35 or fewer CAG repeats, whereas HD is caused by 36 or more repeats. HD and related polyQ expansion diseases are associated with the formation of intraneuronal inclusions (also known as aggregates) by the mutant proteins containing the expanded polyQ tracts. The toxicity of mutant huntingtin is thought to be exposed...

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Section: Discussionmentioning

confidence: 99%

Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and α-Synuclein

Sarkar

Davies

Huang

et al. 2007

Journal of Biological Chemistry

1,017

881

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“…The limited changes in the fluorophore internalization observed when decreasing the cell temperature, suggest that endocytotic pathways, that are sensibly dependent on the temperature [16,17] in the range 4-37 o C, are only partially effective in the upload process of the c-SLNs and that the internalization is also determined by a direct interaction between the membrane and the c-SLNs phospholipids. This picture agrees with previous analyses [10] that showed that the internalization of the c-SLNs carried fluorophore occurs with the modification of the lipid (SLNs) physical and chemical thermodynamic parameters, probably due to their interaction with phospho-lipids (membrane).…”

Section: Eq 3) In Terms Of the Energy Gain ∆Umentioning

confidence: 99%

A biophysical model of intracellular distribution and perinuclear accumulation of particulate matter

Rivolta

Panariti

Collini

et al. 2011

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 AbstractWe have measured in human alveolar cells the cytoplasmic distribution of the fluorophore coumarin-6 carried by Solid Lipid Nanoparticles (SLNs) and observed a perinuclear accumulation of the fluorescence that can be described by a single exponential growth along an ideal line joining the plasma membrane to the nuclear border and by a sigmoidal relationship as a function of time. Intracellular distribution was affected by lowering the temperature from 37 to 4°C and by the disruption of cytoskeleton by cytochalasin D, but it was minimally perturbed by the inhibition of ATP dependent molecular motors. A biophysical model was developed for an accumulation of loaded particles against a diffusion gradient based on a mean field interaction energy, whose origin we ascribe to the actin structure of the cytoskeleton. The estimated value for the load diffusion coefficient was four and two orders of magnitude less than that of free coumarin-6 and of SLNs in aqueous solutions, respectively, suggesting that the load moves within the cell cytoplasm in a form still reminiscent of the nanocarrier structure.

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“…Several mechanisms of hypothermic injury have been proposed, including the loss of ionic homeothese points corresponds to an activation energy of stasis (31,46), the uncoupling of cellular metabolism decreasing temperature. A swelling mechanism could, however, contribute to cell killing below 10°C because (21), lipid phase transitions in membranes (13,26), depolymerization of the cytoskeleton (49,56), and oxidative k increases with decreasing temperature in this range. However, it is unlikely that cell swelling contributes to stress (8,39).…”

Section: Introductionmentioning

confidence: 99%

Endothelial Cell Preservation at 10°C Minimizes Catalytic Iron, Oxidative Stress, and Cold-Induced Injury

Zieger

Gupta

2006

Cell Transplant

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There is growing evidence that oxidative stress plays an important role in mediating the injury induced by hypothermia during the preservation of cells and tissues for clinical or research use. In cardiovascular allografts, endothelial cell loss or injury may lead to impaired control of vascular permeability and tone, thrombosis, and inflammation. We hypothesized that hypothermia-induced damage to the endothelium is linked to increases in intracellular catalytic iron pools and oxidative stress. In this study, bovine aortic endothelial cells and cell culture methods were used to model the response of the endothelium of cardiovascular tissues to hypothermia. Confluent cells were stored at 0°C to 25°C and cell damage was measured by lipid peroxidation (LPO) and lactate dehydrogenase release. Varying the bleomycin-detectible iron (BDI) in cells modulated cold-induced LPO and cell injury. In untreated cells, injury was highest at 0°C and a minimum at 10°C. A similar temperature-dependent trend was found in BDI levels and cell plating efficiencies. Arrhenius plots of cell killing and iron accumulation rates showed biphasic temperature dependence, with minima at 10°C and matching activation energies above and below 10°C. These findings imply that the mechanisms underlying the hypothermic increase in catalytic iron, oxidative stress, and cell killing are the same and that preservation of the endothelium may be optimized at temperatures above those routinely used.

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Temperature dependence of fluid phase endocytosis coincides with membrane properties of pig platelets

Cited by 62 publications

References 37 publications

Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and α-Synuclein

Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and α-Synuclein

A biophysical model of intracellular distribution and perinuclear accumulation of particulate matter

Endothelial Cell Preservation at 10°C Minimizes Catalytic Iron, Oxidative Stress, and Cold-Induced Injury

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