Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ ‐mediated suppression of the host cholesterol transport protein ABCA1

2021 ◽  
Author(s):  
Adam R. Greene ◽  
Katherine A. Owen ◽  
James E. Casanova
Keyword(s):  
Salmonella Typhimurium ◽  
Transport Protein ◽  
Cholesterol Homeostasis ◽  
Cholesterol Transport

Modulation of intestinal cholesterol absorption by high glucose levels: impact on cholesterol transporters, regulatory enzymes, and transcription factors

2008 ◽  
Vol 295 (5) ◽  
pp. G873-G885 ◽  
Author(s):  
Z. Ravid ◽  
M. Bendayan ◽  
E. Delvin ◽  
A. T. Sane ◽  
M. Elchebly ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Protein Expression ◽  
High Glucose ◽  
Cholesterol Absorption ◽  
Cholesterol Homeostasis ◽  
Cholesterol Transport ◽  
Intestinal Cholesterol Absorption ◽  
Cholesterol Uptake ◽  
Glucose Levels

Growing evidence suggests that the small intestine may contribute to excessive postprandial lipemia, which is highly prevalent in insulin-resistant/Type 2 diabetic individuals and substantially increases the risk of cardiovascular disease. The aim of the present study was to determine the role of high glucose levels on intestinal cholesterol absorption, cholesterol transporter expression, enzymes controlling cholesterol homeostasis, and the status of transcription factors. To this end, we employed highly differentiated and polarized cells (20 days of culture), plated on permeable polycarbonate filters. In the presence of [14C]cholesterol, glucose at 25 mM stimulated cholesterol uptake compared with Caco-2/15 cells supplemented with 5 mM glucose ( P < 0.04). Because combination of 5 mM glucose with 20 mM of the structurally related mannitol or sorbitol did not change cholesterol uptake, we conclude that extracellular glucose concentration is uniquely involved in the regulation of intestinal cholesterol transport. The high concentration of glucose enhanced the protein expression of the critical cholesterol transporter NPC1L1 and that of CD36 ( P < 0.02) and concomitantly decreased SR-BI protein mass ( P < 0.02). No significant changes were observed in the protein expression of ABCA1 and ABCG8, which act as efflux pumps favoring cholesterol export out of absorptive cells. At the same time, 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was decreased ( P < 0.007), whereas ACAT activity remained unchanged. Finally, increases were noted in the transcription factors LXR-α, LXR-β, PPAR-β, and PPAR-γ along with a drop in the protein expression of SREBP-2. Collectively, our data indicate that glucose at high concentrations may regulate intestinal cholesterol transport and metabolism in Caco-2/15 cells, thus suggesting a potential influence on the cholesterol absorption process in Type 2 diabetes.

scholarly journals Methotrexate in Atherogenesis and Cholesterol Metabolism

Cholesterol ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Eric Coomes ◽  
Edwin S. L. Chan ◽  
Allison B. Reiss
Keyword(s):  
Cardiovascular Risk ◽  
Cholesterol Metabolism ◽  
Cholesterol Homeostasis ◽  
Cholesterol Transport ◽  
Creb Activation ◽  
Inflammatory Conditions ◽  
Atp Binding Cassette Transporter ◽  
Cox 2 ◽  
Cellular Cholesterol Efflux ◽  
Disease Modifying Antirheumatic Drug

Methotrexate is a disease-modifying antirheumatic drug commonly used to treat inflammatory conditions such as rheumatoid arthritis which itself is linked to increased cardiovascular risk. Treatments that target inflammation may also impact the cardiovascular system. While methotrexate improves cardiovascular risk, inhibition of the cyclooxygenase (COX)-2 enzyme promotes atherosclerosis. These opposing cardiovascular influences may arise from differing effects on the expression of proteins involved in cholesterol homeostasis. These proteins, ATP-binding cassette transporter (ABC) A1 and cholesterol 27-hydroxylase, facilitate cellular cholesterol efflux and defend against cholesterol overload. Methotrexate upregulates expression of cholesterol 27-hydroxylase and ABCA1 via adenosine release, while COX-2 inhibition downregulates these proteins. Adenosine, acting through the A2A and A3 receptors, may upregulate proteins involved in reverse cholesterol transport by cAMP-PKA-CREB activation and STAT inhibition, respectively. Elucidating underlying cardiovascular mechanisms of these drugs provides a framework for developing novel cardioprotective anti-inflammatory medications, such as selective A2A receptor agonists.

Reciprocal regulation of cholesterol and beta amyloid at the subcellular level in Alzheimer’s disease

2012 ◽  
Vol 90 (6) ◽  
pp. 753-764 ◽  
Author(s):  
Elena Posse de Chaves
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholesterol Homeostasis ◽  
Cholesterol Transport ◽  
Reciprocal Regulation ◽  
Beta Peptide ◽  
The Many ◽  
The Relationship ◽  
Aβ Production ◽  
Subcellular Level

Since the discovery that apolipoprotein E, a cholesterol transport protein, is a major risk factor for Alzheimer’s disease (AD) development, there has been a remarkable interest in understanding the many facets of the relationship between cholesterol and AD. Several lines of evidence have demonstrated the importance of cholesterol in amyloid beta peptide (Aβ) production and metabolism, as well as the involvement of Aβ in cholesterol homeostasis. The emerging picture is complex and still incomplete. This review discusses findings that indicate that a reciprocal regulation exists between Aβ and cholesterol at the subcellular level. The pathological impact of such regulation is highlighted.

scholarly journals Peroxisomes in intracellular cholesterol transport: from basic physiology to brain pathology

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Jian Xiao ◽  
Bao-Liang Song ◽  
Jie Luo
Keyword(s):  
Neurodegenerative Diseases ◽  
Cholesterol Homeostasis ◽  
Neurological Deficits ◽  
Cholesterol Transport ◽  
Peroxisome Biogenesis ◽  
Cholesterol Trafficking ◽  
Cholesterol Accumulation ◽  
Peroxisomal Disorders ◽  
Pathological Conditions ◽  
Ether Phospholipids

Peroxisomes are actively involved in the metabolism of various lipids including fatty acids, ether phospholipids, bile acids as well as the processing of reactive oxygen and nitrogen species. Recent studies show that peroxisomes can regulate cholesterol homeostasis by mediating cholesterol transport from the lysosomes to the endoplasmic reticulum and towards primary cilium as well. Disruptions of peroxisome biogenesis or functions lead to peroxisomal disorders that usually involve neurological deficits. Peroxisomal dysfunction is also linked to several neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In many peroxisomal disorders and neurodegenerative diseases, aberrant cholesterol accumulation is frequently encountered yet largely neglected. This review discusses the current understanding of the mechanisms by which peroxisomes facilitate cholesterol trafficking within the cell and the pathological conditions related to impaired cholesterol transport by peroxisomes, with the hope to inspire future development of the treatments for peroxisomal disorders and neurodegenerative diseases.

Impact of Aging on Cholesterol Transport Protein Expression and Steroidogenesis in Rat Testicular Leydig Cells

2008 ◽  
Vol 2 (1) ◽  
pp. 76-85 ◽  
Author(s):  
Zhihong Sun ◽  
Wen-Jun Shen ◽  
Susan-Leers Sucheta ◽  
Salman Azhar
Keyword(s):  
Protein Expression ◽  
Leydig Cells ◽  
Transport Protein ◽  
Cholesterol Transport

scholarly journals ORP1L, ORP1S, and ORP2: Lipid Sensors and Transporters

Contact ◽  
2020 ◽  
Vol 3 ◽  
pp. 251525642095681
Author(s):  
Yvette C. Aw ◽  
Andrew J. Brown ◽  
Jia-Wei Wu ◽  
Hongyuan Yang
Keyword(s):  
Plasma Membrane ◽  
Cholesterol Homeostasis ◽  
Cholesterol Transport ◽  
Lipid Transfer ◽  
Cholesterol Trafficking ◽  
Lipid Transfer Proteins ◽  
Oxysterol Binding Protein ◽  
Membrane Contact ◽  
Related Proteins ◽  
Lipid Sensors

Lipid transfer proteins are crucial for intracellular cholesterol trafficking at sites of membrane contact. In the OSBP/ORPs (oxysterol binding protein and OSBP-related proteins) family of lipid transfer proteins, ORP1L, ORP1S and ORP2 play important roles in cholesterol transport. ORP1L is an endosome/lysosome-anchored cholesterol sensor which may also move cholesterol bidirectionally at the interface between the endoplasmic reticulum and the endosome/lysosome. ORP2 delivers cholesterol to the plasma membrane, driven by PI(4,5)P2 hydrolysis. ORP1S may also transport cholesterol to the plasma membrane, although it is unclear if phosphoinositides are involved. The source of cholesterol delivered to the plasma membrane by ORP1S and ORP2 remains unclear. This review summarises the roles of these proteins in maintaining cellular cholesterol homeostasis and in human disease.

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