Open Access. Powered by Scholars. Published by Universities.®
Social and Behavioral Sciences Commons™
Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 27 of 27
Full-Text Articles in Social and Behavioral Sciences
Structural Characterization Of Clusterin-Chaperone Client Protein Complexes, Amy Wyatt, Justin Yerbury, Mark Wilson
Structural Characterization Of Clusterin-Chaperone Client Protein Complexes, Amy Wyatt, Justin Yerbury, Mark Wilson
Mark R Wilson
Clusterin (CLU) is a potent extracellular chaperone that inhibits protein aggregation and precipitation otherwise caused by physical or chemical stresses (e.g. heat, reduction). This action involves CLU forming soluble high molecular weight (HMW) complexes with the client protein. Other than their unquantified large size, the physical characteristics of these complexes were previously unknown. In this study, HMW CLU-citrate synthase (CS), HMW CLU-fibrinogen (FGN), and HMW CLU-glutathione S-transferase (GST) complexes were generated in vitro, and their structures studied using size exclusion chromatography (SEC), ELISA, SDS-PAGE, dynamic light scattering (DLS), bisANS fluorescence, and circular dichroism spectrophotometry (CD). Densitometry of …
The Extracellular Chaperone Clusterin Sequesters Oligomeric Forms Of The Amyloid-Beta 1-40 Peptide, Priyanka Narayan, Angel Orte, Richard Clarke, Benedetta Bolognesi, Sharon Hook, Kristina Ganzinger, Sarah Meehan, Mark Wilson, Christopher Dobson, David Klenerman
The Extracellular Chaperone Clusterin Sequesters Oligomeric Forms Of The Amyloid-Beta 1-40 Peptide, Priyanka Narayan, Angel Orte, Richard Clarke, Benedetta Bolognesi, Sharon Hook, Kristina Ganzinger, Sarah Meehan, Mark Wilson, Christopher Dobson, David Klenerman
Mark R Wilson
In recent genome-wide association studies, the extracellular chaperone protein, clusterin, has been identified as a newly-discovered risk factor in Alzheimer's disease. We have examined the interactions between human clusterin and the Alzheimer's disease-associated amyloid-β 1-40 peptide (Aβ 1-40), which is prone to aggregate into an ensemble of oligomeric intermediates implicated in both the proliferation of amyloid fibrils and in neuronal toxicity. Using highly sensitive single-molecule fluorescence methods, we have found that Aβ 1-40 forms a heterogeneous distribution of small oligomers (from dimers to 50-mers), all of which interact with clusterin to form long-lived, stable complexes. Consequently, clusterin is able to …
Polyelectrolyte Complex Materials Consisting Of Antibacterial And Cell-Supporting Layers, Khairul Mat Amin, Kerry Gilmore, Jake Matic, Stephen Poon, Mark Walker, Mark Wilson, Marc In Het Panhuis
Polyelectrolyte Complex Materials Consisting Of Antibacterial And Cell-Supporting Layers, Khairul Mat Amin, Kerry Gilmore, Jake Matic, Stephen Poon, Mark Walker, Mark Wilson, Marc In Het Panhuis
Mark R Wilson
The characterization of a polyelectrolyte complex material comprised of two biopolymers, a chitosan upper layer and a gellan gum under layer, is reported. It is shown that the upper layer of chitosan with incorporated levofloxacin displays an antibacterial activity, while the under layer of a gellan gum/TiO2 composite supports the growth of fibroblastic cells.
Sex-Specific Sod Levels And Dna Damage In Painted Dragon Lizards (Ctenophorus Pictus), Mats Olsson, Mo Healey, Cecile Perrin, Mark Wilson, Michael Tobler
Sex-Specific Sod Levels And Dna Damage In Painted Dragon Lizards (Ctenophorus Pictus), Mats Olsson, Mo Healey, Cecile Perrin, Mark Wilson, Michael Tobler
Mark R Wilson
When groups of individuals differ in activities that may influence the production of reactive molecules, such as superoxide, we expect selection to result in congruent upregulation of antioxidant production in the group(s) most at risk of suffering concomitant erosion of essential tissue and biomolecules, such as DNA. We investigate this in a (near) annual lizard species, the Australian painted dragon (Ctenophorus pictus), in which males and females have fundamentally different lifestyles, with males being overtly conspicuous and aggressive, whereas females are placid and camouflaged. When kept in identical conditions to females in captivity, males had higher levels of superoxide dismutase …
Predictors Of Telomere Content In Dragon Lizards, Cissy Ballen, Mo Healey, Mark Wilson, Michael Tobler, Mats Olsson
Predictors Of Telomere Content In Dragon Lizards, Cissy Ballen, Mo Healey, Mark Wilson, Michael Tobler, Mats Olsson
Mark R Wilson
Telomeres shorten as a consequence of DNA replication, in particular in cells with low production of telomerase and perhaps in response to physiological stress from exposure to reactive oxygen species, such as superoxide. This process of telomere attrition is countered by innate antioxidation, such as via the production of superoxide dismutase. We studied the inheritance of telomere length in the Australian painted dragon lizard (Ctenophorus pictus) and the extent to which telomere length covaries with masscorrected maternal reproductive investment, which reflects the level of circulating yolk precursor and antioxidant, vitellogenin. Our predictors of offspring telomere length explained 72 % of …
A Significant Component Of Ageing (Dna Damage) Is Reflected In Fading Breeding Colors: An Experimental Test Using Innate Antioxidant Mimetics In Painted Dragon Lizards, Mats Olsson, Michael Tobler, Mo Healey, Cecile Perrin, Mark Wilson
A Significant Component Of Ageing (Dna Damage) Is Reflected In Fading Breeding Colors: An Experimental Test Using Innate Antioxidant Mimetics In Painted Dragon Lizards, Mats Olsson, Michael Tobler, Mo Healey, Cecile Perrin, Mark Wilson
Mark R Wilson
A decade ahead of their time, von Schantz et al. united sexual selection and free radical biology by identifying causal links between deep-rooted physiological processes that dictate resistance to toxic waste from oxidative metabolism (reactive oxygen species, ROS), and phenotypic traits, such as ornaments.Ten years later, these ideas have still only been tested with indirect estimates of free radical levels (oxidative stress) subsequent to the action of innate and dietary antioxidants. Here, we measure net superoxide (a selection pressure for antioxidant production) and experimentally manipulate superoxide antioxidation using a synthetic mimetic of superoxide dismutase (SOD), Eukarion 134 (EUK). We then …
Amyloid-Β Oligomers Are Sequestered By Both Intracellular And Extracellular Chaperones, P Narayan, Sarah Meehan, John Carver, Mark Wilson, C M Dobson, D Klenerman
Amyloid-Β Oligomers Are Sequestered By Both Intracellular And Extracellular Chaperones, P Narayan, Sarah Meehan, John Carver, Mark Wilson, C M Dobson, D Klenerman
Mark R Wilson
The aberrant aggregation of the amyloid-β peptide into β-sheet rich, fibrillar structures proceeds via a heterogeneous ensemble of oligomeric intermediates that have been associated with neurotoxicity in Alzheimer’s disease (AD). Of particular interest in this context are the mechanisms by which molecular chaperones, part of the primary biological defenses against protein misfolding, influence Aβ aggregation. We have used single-molecule fluorescence techniques to compare the interactions between distinct aggregation states (monomers, oligomers, and amyloid fibrils) of the AD-associated amyloid-β(1–40) peptide, and two molecular chaperones, both of which are upregulated in the brains of patients with AD and have been found colocalized …
Net Superoxide Levels: Steeper Increase With Activity In Cooler Female And Hotter Male Lizards, Cissy Ballen, Mo Healey, Mark Wilson, Michael Tobler, Erik Wapstra, Mats Olsson
Net Superoxide Levels: Steeper Increase With Activity In Cooler Female And Hotter Male Lizards, Cissy Ballen, Mo Healey, Mark Wilson, Michael Tobler, Erik Wapstra, Mats Olsson
Mark R Wilson
"Ectotherms increase their body temperature in response to ambient heat, thereby elevating their metabolic rate. An often inferred consequence of this is an overall upregulation of gene expression and energetic expenditure, and a concomitant increased production of reactive oxygen species (e. g. superoxide) and, perhaps, a shortened lifespan. However, recent work shows that this may be a superficial interpretation. For example, sometimes a reduced temperature may in fact trigger up-regulation of gene expression. We studied temperature and associated activity effects in male and female Australian painted dragon lizards (Ctenophorus pictus) by allowing the lizards to bask for 4 h versus …
Ans Binding Reveals Common Features Of Cytotoxic Amyloid Species, Benedetta Bolognesi, Janet Kumita, Teresa Barros, Elin Esbjorner, Leila Luheshi, Damian Crowther, Mark Wilson, Christopher Dobson, Giorgio Favrin, Justin Yerbury
Ans Binding Reveals Common Features Of Cytotoxic Amyloid Species, Benedetta Bolognesi, Janet Kumita, Teresa Barros, Elin Esbjorner, Leila Luheshi, Damian Crowther, Mark Wilson, Christopher Dobson, Giorgio Favrin, Justin Yerbury
Mark R Wilson
Oligomeric assemblies formed from a variety of disease-associated peptides and proteins have been strongly associated with toxicity in many neurodegenerative conditions, such as Alzheimer's disease. The precise nature of the toxic agents, however, remains still to be established. We show that prefibrillar aggregates of E22G (arctic) variant of the A beta(1-42) peptide bind strongly to 1-anilinonaphthalene 8-sulfonate and that changes in this property correlate significantly with changes in its cytotoxicity. Moreover, we show that this phenomenon is common to other amyloid systems, such as wild-type A beta(1-42), the 159T variant of human lysozyme and an SH3 domain. These findings are …
Polymorphic Ros Scavenging Revealed By Cccp In A Lizard, Mats Olsson, Mark Wilson, Caroline Isaksson, Tobias Uller
Polymorphic Ros Scavenging Revealed By Cccp In A Lizard, Mats Olsson, Mark Wilson, Caroline Isaksson, Tobias Uller
Mark R Wilson
Ingestion of antioxidants has been argued to scavenge circulating reactive molecules (e.g., free radicals), play a part in mate choice (by mediating access to this important resource), and perhaps increase life span. However, recent work has come to question these relationships. We have shown elsewhere in the polychromatic lizard, Ctenophorus pictus, that diet supplementation of carotenoids as antioxidants does not depress circulating natural reactive oxygen species (ROS) levels and leads to no corresponding improvement of color traits. However, a much stronger test would be to experimentally manipulate the ROS levels themselves and assess carotenoid-induced ROS depression. Here, we achieve this …
Variation In Levels Of Reactive Oxygen Species Is Explained By Maternal Identity, Sex And Body-Size-Corrected Clutch Size In A Lizard, Mark Wilson, Mats Olsson, Tobias Uller, Caroline Isaksson, Beth Mott
Variation In Levels Of Reactive Oxygen Species Is Explained By Maternal Identity, Sex And Body-Size-Corrected Clutch Size In A Lizard, Mark Wilson, Mats Olsson, Tobias Uller, Caroline Isaksson, Beth Mott
Mark R Wilson
No abstract provided.
The Chaperone Action Of Clusterin And Its Putative Role In Quality Control Of Extracellular Protein Folding, Amy Wyatt, Justin Yerbury, Stephen Poon, Rebecca Dabbs, Mark Wilson
The Chaperone Action Of Clusterin And Its Putative Role In Quality Control Of Extracellular Protein Folding, Amy Wyatt, Justin Yerbury, Stephen Poon, Rebecca Dabbs, Mark Wilson
Mark R Wilson
The function(s) of clusterin may depend upon its topological location. A variety of intracellular "isoforms" of clusterin have been reported but further work is required to better define their identity. The secreted form of clusterin has a potent ability to inhibit both amorphous and amyloid protein aggregation. In the case of amorphous protein aggregation, clusterin forms stable, soluble high-molecular-weight complexes with misfolded client proteins. Clusterin expression is increased during many types of physiological and pathological stresses and is thought to function as an extracellular chaperone (EC). The pathology of a variety of serious human diseases is thought to arise as …
Effect Of Statins On Serum Apolipoprotein J And Paraoxonase-1 Levels In Patients With Ischemic Heart Disease Undergoing Coronary Angiography, Mark Wilson, Dimitri Mikhailidis, Maria Poulakou, Despina Perrea, Kosmas Paraskevas, Dimitrios Iliopoulos, Serafim Tsitsilonis, Ioannis Vlachos, Sonia-Athena Karabina
Effect Of Statins On Serum Apolipoprotein J And Paraoxonase-1 Levels In Patients With Ischemic Heart Disease Undergoing Coronary Angiography, Mark Wilson, Dimitri Mikhailidis, Maria Poulakou, Despina Perrea, Kosmas Paraskevas, Dimitrios Iliopoulos, Serafim Tsitsilonis, Ioannis Vlachos, Sonia-Athena Karabina
Mark R Wilson
No abstract provided.
Carotenoid Intake Does Not Mediate A Relationship Between Reactive Oxygen Species And Bright Colouration: Experimental Test In A Lizard, Mark Wilson, Mats Olsson, Tobias Uller, Caroline Isaksson, Beth Mott
Carotenoid Intake Does Not Mediate A Relationship Between Reactive Oxygen Species And Bright Colouration: Experimental Test In A Lizard, Mark Wilson, Mats Olsson, Tobias Uller, Caroline Isaksson, Beth Mott
Mark R Wilson
No abstract provided.
Free Radicals Run In Lizard Families, Mark Wilson, Mats Olsson, Tobias Uller, Caroline Isaksson, Beth Mott, Mo Healey, Wanger Thomas
Free Radicals Run In Lizard Families, Mark Wilson, Mats Olsson, Tobias Uller, Caroline Isaksson, Beth Mott, Mo Healey, Wanger Thomas
Mark R Wilson
No abstract provided.
Protease Activation Of A2-Macroglobulin Modulates A Chaperone-Like Action With Broad Specificity, Katie French, Justin Yerbury, Mark Wilson
Protease Activation Of A2-Macroglobulin Modulates A Chaperone-Like Action With Broad Specificity, Katie French, Justin Yerbury, Mark Wilson
Mark R Wilson
α2-Macroglobulin (α2M) is a major human blood glycoprotein best known for its ability to inhibit a broad spectrum of proteases by a unique trapping method. This action induces an “activated” conformation of α2M with an exposed binding site for the low density lipoprotein receptor, facilitating clearance of α2M-protease complexes from the body. This report establishes that protease activation also modulates a potent chaperone-like action of α2M which has broad specificity for proteins partly unfolded as a result of heat or oxidative stress. Protease-mediated activation of α2M abolishes its chaperone-like activity. However, native α2M is able to form soluble complexes with …
The Extracellular Chaperone Clusterin Influences Amyloid Formation And Toxicity By Interacting With Pre-Fibrillar Structures, Justin Yerbury, Stephen Poon, Sarah Meehan, Brianna Thompson, Janet Kumita, Christopher Dobson, Mark Wilson
The Extracellular Chaperone Clusterin Influences Amyloid Formation And Toxicity By Interacting With Pre-Fibrillar Structures, Justin Yerbury, Stephen Poon, Sarah Meehan, Brianna Thompson, Janet Kumita, Christopher Dobson, Mark Wilson
Mark R Wilson
Clusterin is an extracellular chaperone present in all disease-associated extracellular amyloid deposits, however, its roles in amyloid formation and protein deposition in vivo are poorly understood. The current study initially aimed to characterise the effects of clusterin on amyloid formation in vitro by a panel of eight protein substrates. Two of the substrates (Alzheimer's beta peptide and a PI3-SH3 domain) were then used in further experiments to examine the effects of clusterin on amyloid cytotoxicity and to probe the mechanism of clusterin action. We show that clusterin exerts potent effects on amyloid formation, the nature and extent of which vary …
The Extracellular Chaperone Clusterin Potently Inhibits Human Lysozyme Amyloid Formation By Interacting With Prefibrillar Species, Mark Wilson, Justin Yerbury, Stephen Poon, Christopher Dobson, C V Robinson, Elise Stewart, Janet Kumita, Mireille Dumoulin, Gemma Caddy, Christine Hagan
The Extracellular Chaperone Clusterin Potently Inhibits Human Lysozyme Amyloid Formation By Interacting With Prefibrillar Species, Mark Wilson, Justin Yerbury, Stephen Poon, Christopher Dobson, C V Robinson, Elise Stewart, Janet Kumita, Mireille Dumoulin, Gemma Caddy, Christine Hagan
Mark R Wilson
We have studied the effects of the extracellular molecular chaperone, clusterin, on the in vitro aggregation of mutational variants of human lysozyme, including one associated with familial amyloid disease. The aggregation of the amyloidogenic variant I56T is inhibited significantly at clusterin-to-lysozyme ratios as low as 1:80 (i.e. one clusterin molecule per 80 lysozyme molecules). Experiments indicate that under the conditions where inhibition of aggregation occurs, clusterin does not bind detectably to the native or fibrillar states, or to the monomeric transient intermediate known to be a key species in the aggregation reaction. Rather, it seems to interact with oligomeric species …
Effects Of Glycosylation On The Structure And Function Of The Extracellular Chaperone Clusterin, Elise Stewart, Andrew Aquilina, Simon B Easterbrook-Smith, D Murphy-Durland, C Jacobsen, S Moestrup, Mark Wilson
Effects Of Glycosylation On The Structure And Function Of The Extracellular Chaperone Clusterin, Elise Stewart, Andrew Aquilina, Simon B Easterbrook-Smith, D Murphy-Durland, C Jacobsen, S Moestrup, Mark Wilson
Mark R Wilson
Clusterin is the first well characterized, constitutively secreted extracellular chaperone that binds to exposed regions of hydrophobicity on non-native proteins. It may help control the folding state of extracellular proteins by targeting them for receptor-mediated endocytosis and intracellular lysosomal degradation. A notable feature of secreted clusterin is its heavy glycosylation. Although carbohydrate comprises approximately 20−25% of the total mass of the mature molecule, its function is unknown. Results from the current study demonstrate that deglycosylation of human serum clusterin had little effect on its overall secondary structure content but produced a small increase in solvent-exposed hydrophobicity and enhanced the propensity …
Comparison Of Virulence Gene Profiles Between Escherichia Coli Strains Isolated From Healthy And Diarrheic Swine, Mark Wilson, Karl A Bettelheim, X Y Wu, S Driesen, James Chin, Toni Chapman, I Barchia, D Trott
Comparison Of Virulence Gene Profiles Between Escherichia Coli Strains Isolated From Healthy And Diarrheic Swine, Mark Wilson, Karl A Bettelheim, X Y Wu, S Driesen, James Chin, Toni Chapman, I Barchia, D Trott
Mark R Wilson
No abstract provided.
Amyloid Fibril Formation By Bovine Milk Kappa-Casein And Its Inhibition By The Molecular Chaperones Alpha-S And Beta-Casein, Mark Wilson, David Thorn, Agata Rekas, S. L Gras, Christopher Dobson, Sarah Meehan, Cait Macphee, M Sunde
Amyloid Fibril Formation By Bovine Milk Kappa-Casein And Its Inhibition By The Molecular Chaperones Alpha-S And Beta-Casein, Mark Wilson, David Thorn, Agata Rekas, S. L Gras, Christopher Dobson, Sarah Meehan, Cait Macphee, M Sunde
Mark R Wilson
No abstract provided.
Heat Shock Protein 70 Inhibits Alpha-Synuclein Fibril Formation Via Preferential Binding To Prefibrillar Species, Mark Wilson, M. M. Dedmon, J. Christodoulou, Christopher Dobson
Heat Shock Protein 70 Inhibits Alpha-Synuclein Fibril Formation Via Preferential Binding To Prefibrillar Species, Mark Wilson, M. M. Dedmon, J. Christodoulou, Christopher Dobson
Mark R Wilson
No abstract provided.
Lymphotoxin-Beta Receptor-Dependent Genes In Lymph Node And Follicular Dendritic Cell Transcriptomes, Mark Wilson, C. Huber, C. Thielen, Y. Fu, E. Heinen, A Aguzzi, G Miele
Lymphotoxin-Beta Receptor-Dependent Genes In Lymph Node And Follicular Dendritic Cell Transcriptomes, Mark Wilson, C. Huber, C. Thielen, Y. Fu, E. Heinen, A Aguzzi, G Miele
Mark R Wilson
No abstract provided.
The Acute Phase Protein Haptoglobin Is A Mammalian Extracellular Chaperone With An Action Similar To Clusterin, Justin Yerbury, Mark S Rybchyn, Simon B Easterbrook-Smith, C. Henriques, Mark Wilson
The Acute Phase Protein Haptoglobin Is A Mammalian Extracellular Chaperone With An Action Similar To Clusterin, Justin Yerbury, Mark S Rybchyn, Simon B Easterbrook-Smith, C. Henriques, Mark Wilson
Mark R Wilson
Haptoglobin (Hp) is an acidic glycoprotein present in most body fluids of humans and other mammals. Although the functions of Hp are not yet fully understood, the available evidence indicates that it is likely to play an important role in suppressing inflammatory responses. Some earlier work suggested that Hp might be a newly identified member of a small group of extracellular chaperones found at significant levels in human body fluids. Previously, the only well-characterized member of this group was clusterin, which shares functional similarities with the small heat-shock proteins. We report here that Hp specifically inhibited the precipitation of a …
Detecting Mitochondrial Permeability Transition By Confocal Imaging Of Intact Cells Pinocytically Loaded With Calcein, Rachel Jones, Alison Smail, Mark Wilson
Detecting Mitochondrial Permeability Transition By Confocal Imaging Of Intact Cells Pinocytically Loaded With Calcein, Rachel Jones, Alison Smail, Mark Wilson
Mark R Wilson
When studied in vitro, mitochondrial permeability transition (MPT) is associated with an increase in mitochondrial permeability to solutes up to 1500 Da in mass and a loss of electrical potential difference across the inner mitochondrial membrane (delta psi mit). The MPT has been implicated as being important in cellular calcium homeostasis, autophagy and cell death via necrosis and apoptosis. Thus, it is important to develop a valid technique for accurate measurement of this phenomenon in intact cells. We developed a procedure for the detection of MPT in intact cells that avoids disadvantages associated with earlier approaches. In this new technique, …
Evidence That Clusterin Has Discrete Chaperone And Ligand Binding Sites, Johnathon Lakins, Stephen Poon, Simon Easterbrook-Smith, John Carver, Martin Tenniswood, Mark Wilson
Evidence That Clusterin Has Discrete Chaperone And Ligand Binding Sites, Johnathon Lakins, Stephen Poon, Simon Easterbrook-Smith, John Carver, Martin Tenniswood, Mark Wilson
Mark R Wilson
Clusterin is the first identified extracellular mammalian chaperone and binds to a wide variety of partly unfolded, stressed proteins. Clusterin also binds to many different unstressed ligands including the cell surface receptor low density lipoprotein receptor-related protein-2 (LRP-2). It is unknown whether clusterin binds to all of these many ligands via one or more binding sites. Furthermore, the region(s) of clusterin involved in these many binding interactions remain to be identified. As part of an investigation of these issues, we expressed recombinant human clusterin in the yeast Pichia pastoris. The resultant protein had variable proteolytic truncations of the C-terminal region …
Clusterin Is An Atp-Independent Chaperone With Very Broad Substrate Specificity That Stabilizes Stressed Proteins In A Folding-Competent State, Stephen Poon, Simon Easterbrook-Smith, Mark Rybchyn, John Carver, Mark Wilson
Clusterin Is An Atp-Independent Chaperone With Very Broad Substrate Specificity That Stabilizes Stressed Proteins In A Folding-Competent State, Stephen Poon, Simon Easterbrook-Smith, Mark Rybchyn, John Carver, Mark Wilson
Mark R Wilson
We recently reported that the ubiquitous, secreted protein clusterin has chaperone activity in vitro [Humphreys et al. (1999) J. Biol. Chem. 274, 6875−6881]. In this study, we demonstrate that clusterin (i) inhibits stress-induced precipitation of a very broad range of structurally divergent protein substrates, (ii) binds irreversibly via an ATP-independent mechanism to stressed proteins to form solubilized high molecular weight complexes, (iii) lacks detectable ATPase activity, (iv) when acting alone, does not effect refolding of stressed proteins in vitro, and (v) stabilizes stressed proteins in a state competent for refolding by heat shock protein 70 (HSP70). Furthermore, we show that, …