title: Impact of the loss of caveolin-1 on lung mass and cholesterol metabolism in mice with and without the lysosomal cholesterol transporter, Niemann-Pick type C1.
abstract: Caveolin-1 (Cav-1) is a major structural protein in caveolae in the plasma membranes of many cell types, particularly endothelial cells and adipocytes. Loss of Cav-1 function has been implicated in multiple diseases affecting the cardiopulmonary and central nervous systems, as well as in specific aspects of sterol and lipid metabolism in the liver and intestine. Lungs contain an exceptionally high level of Cav-1. Parameters of cholesterol metabolism in the lung were measured, initially in Cav-1-deficient mice (Cav-1(-/-)), and subsequently in Cav-1(-/-) mice that also lacked the lysosomal cholesterol transporter Niemann-Pick C1 (Npc1) (Cav-1(-/-):Npc1(-/-)). In 50-day-old Cav-1(-/-) mice fed a low- or high-cholesterol chow diet, the total cholesterol concentration (mg/g) in the lungs was marginally lower than in the Cav-1(+/+) controls, but due to an expansion in their lung mass exceeding 30%, whole-lung cholesterol content (mg/organ) was moderately elevated. Lung mass (g) in the Cav-1(-/-):Npc1(-/-) mice (0.356±0.022) markedly exceeded that in their Cav-1(+/+):Npc1(+/+) controls (0.137±0.009), as well as in their Cav-1(-/-):Npc1(+/+) (0.191±0.013) and Cav-1(+/+):Npc1(-/-) (0.213±0.022) littermates. The corresponding lung total cholesterol contents (mg/organ) in mice of these genotypes were 6.74±0.17, 0.71±0.05, 0.96±0.05 and 3.12±0.43, respectively, with the extra cholesterol in the Cav-1(-/-):Npc1(-/-) and Cav-1(+/+):Npc1(-/-) mice being nearly all unesterified (UC). The exacerbation of the Npc1 lung phenotype and increase in the UC level in the Cav-1(-/-):Npc1(-/-) mice imply a regulatory role of Cav-1 in pulmonary cholesterol metabolism when lysosomal sterol transport is disrupted.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, USA. Electronic address: dorothy.mundy@utsouthwestern.edu.
authors.forename: Dorothy I
authors.initials: DI
authors.lastname: Mundy
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, USA. Electronic address: adam.lopez@utsouthwestern.edu.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Lopez
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, USA. Electronic address: kenneth.posey@utsouthwestern.edu.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Posey
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, USA. Electronic address: jen-chieh.chuang@UTSouthwestern.edu.
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Chuang
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, USA. Electronic address: charina.ramirez@utsouthwestern.edu.
authors.forename: Charina M
authors.initials: CM
authors.lastname: Ramirez
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, USA. Electronic address: philipp.scherer@utsouthwestern.edu.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, USA. Electronic address: stephen.turley@utsouthwestern.edu.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Turley
mesh_terms: D000818:Animals; D001692:Biological Transport; D021941:Caveolae / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000172:deficiency / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D047908:Intracellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D000077296:Niemann-Pick C1 Protein; D009929:Organ Size; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1; D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins; D002784:Cholesterol
keywords: Cellular cholesterol trafficking; Cholesterol feeding; Cholesterol synthesis; Pulmonary dysfunction; Relative organ weight
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