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Full-Text Articles in Physical Sciences and Mathematics
Cholesterol And Cholesterol Bilayer Domains Inhibit Binding Of Alpha-Crystallin To The Membranes Made Of The Major Phospholipids Of Eye Lens Fiber Cell Plasma Membranes, Raju Timsina, Geraline Trossi-Torres, Matthew O'Dell, Nawal K. Khadka, Laxman Mainali
Cholesterol And Cholesterol Bilayer Domains Inhibit Binding Of Alpha-Crystallin To The Membranes Made Of The Major Phospholipids Of Eye Lens Fiber Cell Plasma Membranes, Raju Timsina, Geraline Trossi-Torres, Matthew O'Dell, Nawal K. Khadka, Laxman Mainali
Physics Faculty Publications and Presentations
The concentration of α-crystallin decreases in the eye lens cytoplasm, with a corresponding increase in membrane-bound α-crystallin during cataract formation. The eye lens’s fiber cell plasma membrane consists of extremely high cholesterol (Chol) content, forming cholesterol bilayer domains (CBDs) within the membrane. The role of high Chol content in the lens membrane is unclear. Here, we applied the continuous-wave electron paramagnetic resonance spin-labeling method to probe the role of Chol and CBDs on α-crystallin binding to membranes made of four major phospholipids (PLs) of the eye lens, i.e., phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylserine (PS), and phosphatidylethanolamine (PE). Small unilamellar vesicles …
Prevention Of Renal Apob Retention Is Protective Against Diabetic Nephropathy: Role Of Tgf-Β Inhibition, Patricia G. Wilson, Joel C. Thompson, Meghan S. Yoder, Richard Charnigo, Lisa R. Tannock
Prevention Of Renal Apob Retention Is Protective Against Diabetic Nephropathy: Role Of Tgf-Β Inhibition, Patricia G. Wilson, Joel C. Thompson, Meghan S. Yoder, Richard Charnigo, Lisa R. Tannock
Internal Medicine Faculty Publications
Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy (DN). We previously demonstrated that renal lipoproteins colocalize with biglycan, a renal proteoglycan. The purpose of this study was to determine whether prevention of renal lipid (apoB) accumulation attenuates DN. Biglycan-deficient and biglycan wild-type Ldlr−/− mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated transforming growth factor-β (TGF-β), in some experiments mice were injected with either the TGF-β-neutralizing antibody, 1D11, or with 13C4, an irrelevant control antibody. Biglycan deficiency had no significant effect …
Cholesterol's Location In Lipid Bilayers, Drew Marquardt, Norbert Kučerka, Stephen R. Wassall, Thad A. Harroun, John Katsaras
Cholesterol's Location In Lipid Bilayers, Drew Marquardt, Norbert Kučerka, Stephen R. Wassall, Thad A. Harroun, John Katsaras
Chemistry and Biochemistry Publications
It is well known that cholesterol modifies the physical properties of lipid bilayers. For example, the much studied liquid-ordered Lo phase contains rapidly diffusing lipids with their acyl chains in the all trans configuration, similar to gel phase bilayers. Moreover, the Lo phase is commonly associated with cholesterol-enriched lipid rafts, which are thought to serve as platforms for signaling proteins in the plasma membrane. Cholesterol's location in lipid bilayers has been studied extensively, and it has been shown – at least in some bilayers – to align differently from its canonical upright orientation, where its hydroxyl group is in the …
Neutron Scattering At The Intersection Of Heart Health Science And Biophysics, Drew Marquardt, Richard J. Alsop, Maikel C. Rheinstädter, Thad A. Harroun
Neutron Scattering At The Intersection Of Heart Health Science And Biophysics, Drew Marquardt, Richard J. Alsop, Maikel C. Rheinstädter, Thad A. Harroun
Chemistry and Biochemistry Publications
There is an urgent quest for improved heart health. Here, we review how neutron radiation can provide insight into the molecular basis of heart health. Lower cholesterol, a daily intake of aspirin and supplemental vitamin E are argued to all improve heart health. However, the mechanisms behind these common regimens, and others, are not entirely understood. It is not clear why a daily intake of aspirin can help some people with heart disease, and the benefits of vitamin E in the treatment of reperfusion injury have been heavily debated. The molecular impact of cholesterol in the body is still a …
Aspirin Inhibits Formation Of Cholesterol Rafts In Fluid Lipid Membranes, Richard J. Alsop, Laura Toppozini, Drew Marquardt, Norbert Kučerka, Thad A. Harroun, Maikel C. Rheinstädter
Aspirin Inhibits Formation Of Cholesterol Rafts In Fluid Lipid Membranes, Richard J. Alsop, Laura Toppozini, Drew Marquardt, Norbert Kučerka, Thad A. Harroun, Maikel C. Rheinstädter
Chemistry and Biochemistry Publications
Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin …
Wild Type And Tangier Disease Abca1 Mutants Modulate Cellular Amyloid-Beta Production Independent Of Cholesterol Efflux Activity, Kim S. Woojin, Andrew F. Hill, Michael L. Fitzgerald, Mason W. Freeman, Genevieve Evin, Brett Garner
Wild Type And Tangier Disease Abca1 Mutants Modulate Cellular Amyloid-Beta Production Independent Of Cholesterol Efflux Activity, Kim S. Woojin, Andrew F. Hill, Michael L. Fitzgerald, Mason W. Freeman, Genevieve Evin, Brett Garner
Faculty of Science - Papers (Archive)
Cerebral amyloid-β (Aβ) deposition is a critical feature of Alzheimer’s disease. Aβ is derived from the amyloid-β protein precursor (AβPP) via two sequential cleavages that are mediated by β-secretase and the γ-secretase complex. Such amyloidogenic AβPP processing occurs in lipid raft microdomains of cell membranes and it is thought that modulating the distribution of lipids in rafts may regulate AβPP processing and Aβ production. Certain ATP-binding cassette (ABC) transporters regulate lipid transport across cell membranes and, as recent studies reveal, within membrane microdomains. ABCA1 also regulates Aβ metabolism in the brain although its direct impact on AβPP remains an open …
Detection And Quantification Of Tear Phospholipids And Cholesterol In Contact Lens Deposits: The Effect Of Contact Lens Material And Lens Care Solution, Jennifer Saville, Zhenjun Zhao, Mark D.P. Willcox, Stephen J. Blanksby, Todd W. Mitchell
Detection And Quantification Of Tear Phospholipids And Cholesterol In Contact Lens Deposits: The Effect Of Contact Lens Material And Lens Care Solution, Jennifer Saville, Zhenjun Zhao, Mark D.P. Willcox, Stephen J. Blanksby, Todd W. Mitchell
Faculty of Science - Papers (Archive)
PURPOSE. To examine the deposition of tear phospholipids and cholesterol onto worn contact lenses and the effect of lens material and lens care solution. METHODS. Lipids were extracted from tears and worn contact lenses using 2: 1 chloroform: methanol and the extract washed with aqueous ammonium acetate, before analysis by electrospray ionization tandem mass spectrometry (ESI-MS/MS). RESULTS. Twenty-three molecular lipids from the sphingomyelin (SM) and phosphatidylcholine (PC) classes were detected in tears, with total concentrations of each class determined to be 5 +/- 1 pmol/mu L (similar to 3.8 mu g/mL) and 6 +/- 1 pmol/mu L (similar to 4.6 …
The Niemann-Pick Type C2 Protein Loads Isoglobotrihexosylceramide Onto Cd1d Molecules And Contributes To The Thymic Selection Of Nkt Cells, Paul B. Savage, Nicolas Schrantz, Yuval Sagiv, Yang Liu, Albert Bendelac, Luc Teyton
The Niemann-Pick Type C2 Protein Loads Isoglobotrihexosylceramide Onto Cd1d Molecules And Contributes To The Thymic Selection Of Nkt Cells, Paul B. Savage, Nicolas Schrantz, Yuval Sagiv, Yang Liu, Albert Bendelac, Luc Teyton
Faculty Publications
The Niemann-Pick type C2 (NPC2) protein is a small, soluble, lysosomal protein important for cholesterol and sphingolipid transport in the lysosome. The immunological phenotype of NPC2-deficient mice was limited to an impaired thymic selection of Valpha 14 natural killer T cells (NKT cells) and a subsequent reduction of NKT cells in the periphery. The remaining NKT cells failed to produce measurable quantities of interferon-gamma in vivo and in vitro after activation with alpha-galactosylceramide. In addition, thymocytes and splenocytes from NPC2-deficient mice were poor presenters of endogenous and exogenous lipids to CD1d-restricted Valpha 14 hybridoma cells. Importantly, we determined that similar …