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Cholesterol Modulation of BK (MaxiK; Slo1) Channels
Published in Qiu-Xing Jiang, New Techniques for Studying Biomembranes, 2020
Alex M. Dopico, Anna N. Bukiya, Kelsey North
In native cellular membranes, including vascular myocytes, BK channels tend to reside within CLR-rich lipid rafts (Dopico and Tigyi, 2007; Sones et al., 2010; Dopico et al., 2012). Modification of CLR levels is expected to alter membrane microdomains, including CLR-rich lipid domains, and sphingolipid distribution (Dopico and Tigyi, 2007; Lingwood, 2011). Thus, one of the possible explanations for CLR-ethanol interaction in controlling BK channel activity arises from CLR modification of lipid rafts. However, CLR modification of BK channel ethanol sensitivity is observed in artificial bilayer systems (see below) of lipid composition that do not enable raft formation (Crowley et al., 2003; Bukiya et al., 2011b). These findings suggest that raft disruption is not a main contributor to CLR modification of the BK channel’s ethanol sensitivity.
Molecular and Cellular Pathogenesis of Systemic Lupus Erythematosus
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
George C. Tsokos, Yuang-Taung Juang, Christos G. Tsokos, Madhusoodana P. Nambiar
The T cell receptor ζ chain associated with the detergent-insoluble fraction is distributed between cytoskeleton as well as lipid-rich membrane microdomains, composed primarily of sphingolipids and cholesterol, and an enriched subset of proteins that float laterally as ‘rafts’ within the plasma membrane.38 Lipid rafts are preformed functional modules that serve as platforms for signal transduction and membrane trafficking. Recent data indicate that lipid rafts are crucial for effecting T cell receptor signal transduction.39,40 T cell receptor engagement leads to translocation and concentration of tyrosine phosphorylated T cell receptor ζ chain and downstream signal transduction molecules within lipid rafts.41 Conversely, perturbation of the structural integrity of lipid rafts inhibits T cell receptor-induced protein tyrosine phosphorylation and calcium flux.40,42
Lipid Raft Alteration and Functional Impairment in Aged Neuronal Membranes
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Julie Colin, Lynn Gregory-Pauron, Frances T. Yen, Thierry Oster, Catherine Malaplate-Armand
Caveolae were the first membrane microdomains identified and the only ones identifiable by their morphology and observable by microscopy. Caveolae are membrane invaginations, with a diameter of 25–150 nm, present in the Trans-Golgian network, exocytosis vesicles, ER, and plasma membrane [123]. Morphologically, they are abundant in the endothelium, muscle cells, adipocytes, and pulmonary epithelial cells [123–125]. Studies have also revealed that these structures are present in the central nervous system (CNS) [126,127]. Caveolae are structures rich in sphingolipids and cholesterol, as well as caveolin and cavine [107,108,128,129]. These caveolae are in particular involved in the transcytosis of molecules in the endothelial cells and in the endocytosis of bacterial toxins [104]. In the brain, the restrictive nature of the BBB requires cellular machinery to transfer and deliver macromolecules to the brain, which involved transcytosis for which the caveolae could play a role. Indeed, they interact in particular in the endocytosis of the plasma membrane receptors and their specific ligand such as insulin, transferrin, or lipoproteins [130], and in a small proportion, leptin [131].
Genistein prevents the decrease in ganglioside levels induced by amyloid-beta in the frontal cortex of rats
Published in Neurological Research, 2022
Fernanda dos Santos Petry, Juliana Bender Hoppe, Caroline Peres Klein, Bernardo Gindri dos Santos, Régis Mateus Hözer, Christianne Gazzana Salbego, Vera Maria Treis Trindade
The AD pathogenesis is closely related to changes in the lipid homeostasis, which can severely affect the physicochemical properties of cell membranes [4,5]. Gangliosides are sialic acid-containing glycosphingolipids, present in high concentrations in neuronal cell membranes, which play important roles in memory formation, neuritogenesis and synaptic transmission. Moreover, they are involved in cell differentiation and growth, ion channel modulation, and intercellular signaling [6]. Phospholipids exert structural functions in the membrane, also participating in cell signaling. Cholesterol, in turn, is an essential component for the structure and function of cell membranes, modulating their physicochemical properties and contributing to the formation of lipid rafts, specialized membrane microdomains that compartmentalize cellular processes [7]. Increasing evidence indicates that the Aβ peptide can alter the composition and structure of cell membranes, impairing neuronal functions [8,9].
An update on synthetic high-density lipoprotein-like nanoparticles for cancer therapy
Published in Expert Review of Anticancer Therapy, 2019
Stephen E. Henrich, C. Shad Thaxton
To deepen our understanding of the clinical correlation between reduced HDL-C and cancer risk with an eye toward therapy, it is important to understand the underlying biology of cholesterol homeostasis in the setting of cancer. Cholesterol is an essential component of the mammalian cell membrane and is required to maintain plasma membrane fluidity, stability, and organization [25,26]. As a result, cancer cells require a steady diet of cholesterol to enable their rapid proliferation. Cholesterol is also a precursor in the synthesis of various hormones and vitamins that are required for cell proliferation and maintenance [26–28]. Prostate cancer, breast cancer, adrenocortical carcinoma and other tumors are highly dependent upon sterol-derived hormones for their growth; and these tumors therefore often have a vociferous appetite for cholesterol [29]. Additionally, cholesterol can be found at high densities in specialized regions of the plasma membrane known as lipid rafts. These membrane microdomains serve as scaffolds for protein assemblies, and thereby regulate a host of ligand-receptor interactions and downstream intracellular signaling processes, many of which are hi-jacked in cancer cells. One instance of this is lipid raft-dependent B cell receptor signaling in B cell lymphomas, which can be inhibited by targeted reduction of cellular cholesterol [30–32]. The fact that synthetic HDLs directly induce cell death in lymphoma cells via this mechanism also provides evidence that HDLs may play a causal role in slowing the progression of malignancy in cancer patients.
Advances and challenges in understanding the role of the lipid raft proteome in human health
Published in Expert Review of Proteomics, 2018
Ahmed Mohamed, Harley Robinson, Pablo Joaquin Erramouspe, Michelle M Hill
Membrane microdomains are biophysical manifestations of lipid phase separation which occurs in cellular membranes containing a mixture of lipids.Although ‘lipid raft’ has been used to denote the liquid-ordered (less fluid) phase characterized by enriched cholesterol and sphingolipids at the plasma membrane, intracellular rafts have been well characterized as mediating lipid trafficking and inter-organellar signaling.Isolation of pure lipid rafts for proteomics remains a significant technical challenge. Additional strategies should be incorporated in the experimental design, such as comparative proteomics and/or incorporation of subcellular fractionation.Lipid rafts are implicated in numerous diseases and health conditions, with varying levels of evidence. Further research is needed to clarify the role of lipids and lipid raft proteins in pathology, to enable the development of prevention and treatment strategies.