Cholesterol homeostasis: How do cells sense sterol excess?

Howe, Vicky; Sharpe, Laura J.; Alexopoulos, Stephanie J.; Kunze, Sarah V.; Chua, Ngee Kiat; Li, Dianfan; Brown, Andrew

doi:10.1016/j.chemphyslip.2016.02.011

Cited by 62 publications

(66 citation statements)

References 74 publications

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“…Cholesterol, by virtue of its planar 4-ring structure and asymmetric decoration with a hydroxyl group, plays a fundamental role in determining membrane integrity and fluidity in eukaryotic cells [1–3]. Vesicular and non-vesicular trafficking of cholesterol within cells maintains a range of cholesterol content across different intracellular membranes.…”

Section: Intracellular Sterol Flux: Rheostat Of Innate and Adaptive Imentioning

confidence: 99%

The Intracellular Cholesterol Landscape: Dynamic Integrator of the Immune Response

Fessler

2016

Trends in Immunology

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Cholesterol has typically been considered an exogenous, disease-related factor in immunity; however, recent literature suggests that a paradigm shift is in order. Sterols are now recognized to ligate several immune receptors. Altered flux through the mevalonic acid synthesis pathway also appears to be a required event in the antiviral interferon response of macrophages and in the activation, proliferation, and differentiation of T cells. In this review, evidence is discussed that suggests an intrinsic, ‘professional’ role for sterols and oxysterols in macrophage and T cell immunity. Host defense may have been the original selection pressure behind the development of mechanisms for intracellular cholesterol homeostasis. Functional coupling between sterol metabolism and immunity has fundamental implications for health and disease.

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Section: Intracellular Sterol Flux: Rheostat Of Innate and Adaptive Imentioning

confidence: 99%

The Intracellular Cholesterol Landscape: Dynamic Integrator of the Immune Response

Fessler

2016

Trends in Immunology

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“…Cholesterol is an abundant component of plasma membranes, being essential for mammalian cell viability and proliferation (Kulig et al 2016;Howe et al 2016). The structure of cholesterol molecules, with a flat and stiff steroid moiety linked to a hydroxyl group (Fig.…”

Section: Cholesterolmentioning

confidence: 99%

“…The structure of cholesterol molecules, with a flat and stiff steroid moiety linked to a hydroxyl group (Fig. 1), affects membrane packing, elasticity and accessibility to small water-soluble molecules (Kulig et al 2016;Howe et al 2016). Hence, cholesterol is involved in several biological processes by altering the properties of lipid bilayers: it participates in lipid nanodomain formation (Edidin 2003;Simons and Sampaio 2011), regulates protein functions (Epand 2006;Kuwabara and Labouesse 2002) and is a precursor of steroid hormones and bile acids (Chiang 2004).…”

Section: Cholesterolmentioning

confidence: 99%

Structural insights on biologically relevant cationic membranes by ESR spectroscopy

et al. 2017

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Cationic bilayers have been used as models to study membrane fusion, templates for polymerization and deposition of materials, carriers of nucleic acids and hydrophobic drugs, microbicidal agents and vaccine adjuvants. The versatility of these membranes depends on their structure. Electron spin resonance (ESR) spectroscopy is a powerful technique that employs hydrophobic spin labels to probe membrane structure and packing. The focus of this review is the extensive structural characterization of cationic membranes prepared with dioctadecyldimethylammonium bromide or diC14-amidine to illustrate how ESR spectroscopy can provide important structural information on bilayer thermotropic behavior, gel and fluid phases, phase coexistence, presence of bilayer interdigitation, membrane fusion and interactions with other biologically relevant molecules.

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“…In total, 126 GWAS have been performed on CHL related phenotypes in humans and animal model species (https://www.ebi.ac.uk/gwas/search?query=cholesterol, accessed on 09 th January, 2018). Although mechanisms regulating CHL have been intensively studied in humans 15–18 , few studies have been devoted to the genetics of CHL in livestock species. In cows, several gene expression/proteomics studies have reported genes with potential involvement in milk CHL concentration/metabolism 19–27 but their actual roles and associated SNPs with CHL content in milk have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Genome wide association study identifies novel potential candidate genes for bovine milk cholesterol content

Ngoc

Schenkel

Miglior

et al. 2018

Sci Rep

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This study aimed to identify single nucleotide polymorphisms (SNPs) associated with milk cholesterol (CHL) content via a genome wide association study (GWAS). Milk CHL content was determined by gas chromatography and expressed as mg of CHL in 100 g of fat (CHL_fat) or in 100 mg of milk (CHL_milk). GWAS was performed with 1,183 cows and 40,196 SNPs using a univariate linear mixed model. Two and 20 SNPs were significantly associated with CHL_fat and CHL_milk, respectively. The important regions for CHL_fat and CHL_milk were at 41.9 Mb on chromosome (BTA) 17 and 1.6–3.2 Mb on BTA 14, respectively. DGAT1, PTPN1, INSIG1, HEXIM1, SDS, and HTR5A genes, also known to be associated with human plasma CHL phenotypes, were identified as potential candidate genes for bovine milk CHL. Additional new potential candidate genes for milk CHL were RXFP1, FAM198B, TMEM144, CXXC4, MAML2 and CDH13. Enrichment analyses suggested that identified candidate genes participated in cell-cell signaling processes and are key members in tight junction, focal adhesion, Notch signaling and glycerolipid metabolism pathways. Furthermore, identified transcription factors such as PPARD, LXR, and NOTCH1 might be important in the regulation of bovine milk CHL content. The expression of several positional candidate genes (such as DGAT1, INSIG1 and FAM198B) and their correlation with milk CHL content were further confirmed with RNA sequence data from mammary gland tissues. This is the first GWAS on bovine milk CHL. The identified markers and candidate genes need further validation in a larger cohort for use in the selection of cows with desired milk CHL content.

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Cholesterol homeostasis: How do cells sense sterol excess?

Cited by 62 publications

References 74 publications

The Intracellular Cholesterol Landscape: Dynamic Integrator of the Immune Response

The Intracellular Cholesterol Landscape: Dynamic Integrator of the Immune Response

Structural insights on biologically relevant cationic membranes by ESR spectroscopy

Genome wide association study identifies novel potential candidate genes for bovine milk cholesterol content

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