Редактирование: ABCG1

ATP-binding cassette sub-family G member 1 (EC 7.6.2.-) (ATP-binding cassette transporter 8) (White protein homolog) [ABC8] [WHT1]

==Publications==

{{medline-entry
|title=Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29946056
|abstract=Photoreceptors have high intrinsic metabolic demand and are exquisitely sensitive to metabolic perturbation. In addition, they shed a large portion of their outer segment lipid membranes in a circadian manner, increasing the metabolic burden on the outer retina associated with the resynthesis of cell membranes and disposal of the cellular cargo. Here, we demonstrate that deletion of both [[ABCA1]] and [[ABCG1]] in rod photoreceptors leads to age-related accumulation of cholesterol metabolites in the outer retina, photoreceptor dysfunction, degeneration of rod outer segments, and ultimately blindness. A high-fat diet significantly accelerates rod neurodegeneration and vision loss, further highlighting the role of lipid homeostasis in regulating photoreceptor neurodegeneration and vision.
|mesh-terms=* ATP Binding Cassette Transporter 1
* ATP Binding Cassette Transporter, Subfamily G, Member 1
* Aging
* Animals
* Cholesterol
* Gene Deletion
* Mice
* Retinal Cone Photoreceptor Cells
* Retinal Rod Photoreceptor Cells
* Vision, Ocular
|keywords=* ATP binding cassette transporter G1
* aging
* cholesterol/dietary
* cholesterol/efflux
* eye/retina
* neurons
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071770
}}
{{medline-entry
|title=Elevated COX2 expression and PGE2 production by downregulation of RXRα in senescent macrophages.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24051096
|abstract=Increased systemic level of inflammatory cytokines leads to numerous age-related diseases. In senescent macrophages, elevated prostaglandin E2 (PGE2) production contributes to the suppression of T cell function with aging, which increases the susceptibility to infections. However, the regulation of these inflammatory cytokines and PGE2 with aging still remains unclear. We have verified that cyclooxygenase (COX)-2 expression and PGE2 production are higher in LPS-stimulated macrophages from old mice than that from young mice. Downregulation of RXRα, a nuclear receptor that can suppress NF-κB activity, mediates the elevation of COX2 expression and PGE2 production in senescent macrophages. We also have found less induction of [[ABCA1]] and [[ABCG1]] by RXRα agonist in senescent macrophages, which partially accounts for high risk of atherosclerosis in aged population. Systemic treatment with RXRα antagonist HX531 in young mice increases COX2, [[TNF]]-α, and IL-6 expression in splenocytes. Our study not only has outlined a mechanism of elevated NF-κB activity and PGE2 production in senescent macrophages, but also provides RXRα as a potential therapeutic target for treating the age-related diseases.
|mesh-terms=* Aging
* Animals
* Cell Line
* Cellular Senescence
* Cyclooxygenase 2
* Dinoprostone
* Down-Regulation
* Lipopolysaccharides
* Macrophages
* Mice
* Mice, Inbred C57BL
* NF-kappa B
* Retinoid X Receptor alpha
* Up-Regulation
|keywords=* 9-cis-retinoid acid
* 9cRA
* ABCA1
* ABCG1
* ATP-binding cassette transporter A1
* ATP-binding cassette transporter G1
* Aging
* COX2
* Macrophage
* NF-κB
* PGE2
* RXR
* RXRα
* TLR
* cyclooxygenase 2
* prostaglandin E2
* retinoid X receptor alpha
* toll-like receptor
|full-text-url=https://sci-hub.do/10.1016/j.bbrc.2013.09.047
}}
{{medline-entry
|title=Differential expression and function of [[ABCG1]] and [[ABCG4]] during development and aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19633360
|abstract=[[ABCG1]] and [[ABCG4]] are highly homologous members of the ATP binding cassette (ABC) transporter family that regulate cellular cholesterol homeostasis. In adult mice, [[ABCG1]] is known to be expressed in numerous cell types and tissues, whereas [[ABCG4]] expression is limited to the central nervous system (CNS). Here, we show significant differences in expression of these two transporters during development. Examination of beta-galactosidase-stained tissue sections from Abcg1(-/-)LacZ and Abcg4(-/-)LacZ knockin mice shows that [[ABCG4]] is highly but transiently expressed both in hematopoietic cells and in enterocytes during development. In contrast, [[ABCG1]] is expressed in macrophages and in endothelial cells of both embryonic and adult liver. We also show that [[ABCG1]] and [[ABCG4]] are both expressed as early as E12.5 in the embryonic eye and developing CNS. Loss of both [[ABCG1]] and [[ABCG4]] results in accumulation in the retina and/or brain of oxysterols, in altered expression of liver X receptor and sterol-regulatory element binding protein-2 target genes, and in a stress response gene. Finally, behavioral tests show that Abcg4(-/-) mice have a general deficit in associative fear memory. Together, these data indicate that loss of [[ABCG1]] and/or [[ABCG4]] from the CNS results in changes in metabolic pathways and in behavior.
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily G
* ATP Binding Cassette Transporter, Subfamily G, Member 1
* ATP-Binding Cassette Transporters
* Aging
* Animals
* Behavior, Animal
* Brain
* Central Nervous System
* Conditioning, Classical
* Embryo, Mammalian
* Fear
* Gene Expression Regulation, Developmental
* Lipoproteins
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Microscopy, Electron, Transmission
* Retina
* beta-Galactosidase

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789777
}}
{{medline-entry
|title=Age-associated decrease of high-density lipoprotein-mediated reverse cholesterol transport activity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19405812
|abstract=High-density lipoproteins (HDL) are considered atheroprotective in contrast to low-density lipoproteins (LDL), which are atherogenic in their oxidized form. A growing body of evidence suggests that HDL exert part of their antiatherogenic effect by counteracting LDL oxidation as well as their proinflammatory effect. However, a number of studies, carried over the past 30 years, have shown that cholesterol efflux plays a major role in the atheroprotective effects of HDL and cholesterol homeostasis. These studies have further identified the scavenger receptor type B-I (SR-BI), the adenosine triphosphate (ATP)-binding cassette transporters ATP-binding cassette subfamily A1 ([[ABCA1]]), ATP-binding cassette subfamily G1 ([[ABCG1]]) and [[ABCG4]], the liver X receptor/retinoid X receptor (LXR/RXR) and peroxisome proliferator-activated receptorgamma(PPAR gamma) transcription factors, the HDL components apolipoprotein A-I (apoA-I), lecithin-cholesterol acyltransferase (LCAT), and phospholipids as additional mediators of cholesterol transport. Cholesterol efflux occurs via three independent pathways: (1) aqueous diffusion, (2) nonspecific efflux via SR-BI receptors, and (3) specific efflux via cholesterol-responsive members of the ABC superfamily. Whereas aqueous diffusion and scavenger receptor class B, type I (SR-BI)-mediated efflux transport free cholesterol to a wide variety of cholesterol acceptors (particles containing phospholipids, HDL, and lipidated apo-lipoproteins; LDL, etc), the [[ABCA1]] pathway mediates the transport of cholesterol in a unidirectional manner, mainly to lipid-poor apoA-I. In contrast, the [[ABCG1]] pathway is responsible for the transport of cholesterol to all the subfamily members of HDL. Although HDL-mediated cholesterol efflux is apoA-I-dependent, recent studies have suggested an involvement of the enzyme paraoxonase 1 ([[PON1]]). Cholesterol efflux is carried on by a number of factors such as genetic mutations, smoking, stress, and high-fat diets. It is attenuated with aging due to changes in the composition and structure of HDL, especially the phosphatidylcholine/sphingomyelin ratio, the fluidity of the phospholipidic layer, the concentration of apoA-I, and the activity of [[PON1]]. This review summarizes the findings that cholesterol homeostasis is disrupted with aging as a consequence of dysfunctional cholesterol efflux and the impairment of physiological functions.
|mesh-terms=* ATP-Binding Cassette Transporters
* Aging
* Animals
* Biological Transport
* Cardiovascular Diseases
* Cholesterol
* Humans
* Lipoproteins, HDL

|full-text-url=https://sci-hub.do/10.1089/rej.2009.0840
}}
{{medline-entry
|title=LXR signaling couples sterol metabolism to proliferation in the acquired immune response.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18614014
|abstract=Cholesterol is essential for membrane synthesis; however, the mechanisms that link cellular lipid metabolism to proliferation are incompletely understood. We demonstrate here that cellular cholesterol levels in dividing T cells are maintained in part through reciprocal regulation of the LXR and SREBP transcriptional programs. T cell activation triggers induction of the oxysterol-metabolizing enzyme [[SULT2B1]], consequent suppression of the LXR pathway for cholesterol transport, and promotion of the SREBP pathway for cholesterol synthesis. Ligation of LXR during T cell activation inhibits mitogen-driven expansion, whereas loss of LXRbeta confers a proliferative advantage. Inactivation of the sterol transporter [[ABCG1]] uncouples LXR signaling from proliferation, directly linking sterol homeostasis to the antiproliferative action of LXR. Mice lacking LXRbeta exhibit lymphoid hyperplasia and enhanced responses to antigenic challenge, indicating that proper regulation of LXR-dependent sterol metabolism is important for immune responses. These results implicate LXR signaling in a metabolic checkpoint that modulates cell proliferation and immunity.
|mesh-terms=* Aging
* Animals
* Cell Proliferation
* DNA-Binding Proteins
* Humans
* Liver X Receptors
* Lymphocyte Activation
* Mice
* Mice, Inbred C57BL
* Orphan Nuclear Receptors
* Receptors, Cytoplasmic and Nuclear
* Signal Transduction
* Sterol Regulatory Element Binding Protein 2
* Sterols
* T-Lymphocytes

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2626438
}}
{{medline-entry
|title=Distinct spatio-temporal expression of ABCA and ABCG transporters in the developing and adult mouse brain.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16181433
|abstract=Using in situ hybridization for the mouse brain, we analyzed developmental changes in gene expression for the ATP-binding cassette (ABC) transporter subfamilies [[ABCA1]]-4 and 7, and [[ABCG1]], 2, 4, 5 and 8. In the embryonic brains, [[ABCA1]] and A7 were highly expressed in the ventricular (or germinal) zone, whereas [[ABCA2]], A3 and G4 were enriched in the mantle (or differentiating) zone. At the postnatal stages, [[ABCA1]] was detected in both the gray and white matter and in the choroid plexus. On the other hand, [[ABCA2]], A3 and A7 were distributed in the gray matter. In addition, marked up-regulation of [[ABCA2]] occurred in the white matter at 14 days-of-age when various myelin protein genes are known to be up-regulated. In marked contrast, [[ABCA4]] was selective to the choroid plexus throughout development. [[ABCG1]] was expressed in both the gray and white matters, whereas [[ABCG4]] was confined to the gray matter. [[ABCG2]] was diffusely and weakly detected throughout the brain at all stages examined. Immunohistochemistry of [[ABCG2]] showed its preferential expression on the luminal membrane of brain capillaries. Expression signals for [[ABCG5]] and G8 were barely detected at any stages. The distinct spatio-temporal expressions of individual ABCA and G transporters may reflect their distinct cellular expressions in the developing and adult brains, presumably, to regulate and maintain lipid homeostasis in the brain.
|mesh-terms=* ATP-Binding Cassette Transporters
* Aging
* Animals
* Animals, Newborn
* Brain
* Embryo, Mammalian
* Immunohistochemistry
* In Situ Hybridization
* Mice
* Mice, Inbred C57BL
* Tissue Distribution

|full-text-url=https://sci-hub.do/10.1111/j.1471-4159.2005.03369.x
}}
{{medline-entry
|title=LXRbeta is required for adipocyte growth, glucose homeostasis, and beta cell function.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15831500
|abstract=Liver X receptors (LXR) alpha and beta are nuclear oxysterol receptors with established roles in cholesterol, lipid, and carbohydrate metabolism. Although LXRs have been extensively studied in liver and macrophages, the importance for development and metabolism of other tissues and cell types is not as well characterized. We demonstrate here that although LXRalpha and LXRbeta are not required for adipocyte development per se, LXRbeta is required for the increase in adipocyte size that normally occurs with aging and diet-induced obesity. Similar food intake and oxygen consumption in LXRbeta-/- mice suggests that reduced storage of lipid in adipose tissue is not due to altered energy balance. Despite reduced amounts of adipose tissue, LXRbeta-/- mice on a chow diet have insulin sensitivity and levels of adipocyte hormones similar to wild type mice. However, these mice are glucose-intolerant due to impaired glucose-induced insulin secretion. Lipid droplets in pancreatic islets may result from accumulation of cholesterol esters as analysis of islet gene expression reveals that LXRbeta is required for expression of the cholesterol transporters, [[ABCA1]] and [[ABCG1]]. Our data establish novel roles for LXRbeta in adipocyte growth, glucose homeostasis, and beta cell function.
|mesh-terms=* Adipocytes
* Adipose Tissue
* Aging
* Animals
* Body Composition
* Carbohydrate Metabolism
* Cholesterol
* DNA-Binding Proteins
* Diet
* Glucose
* Immunoassay
* Insulin
* Islets of Langerhans
* Lipid Metabolism
* Liver
* Liver X Receptors
* Macrophages
* Male
* Mice
* Mice, Transgenic
* Obesity
* Orphan Nuclear Receptors
* Oxygen
* Oxygen Consumption
* Pyruvic Acid
* Receptors, Cytoplasmic and Nuclear
* Reverse Transcriptase Polymerase Chain Reaction
* Time Factors

|full-text-url=https://sci-hub.do/10.1074/jbc.M412564200
}}