Zarbock, Ralf and Kaltenborn, Eva and Frixel, Sabrina and Wittmann, Thomas and Liebisch, Gerhard and Schmitz, Gerd and Griese, Matthias (2015) ABCA3 protects alveolar epithelial cells against free cholesterol induced cell death. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1851 (7). pp. 987-995. ISSN 1388-1981, 0006-3002
Full text not available from this repository. (Request a copy)Abstract
Diffuse parenchymal lung diseases (DPLDs) are characterized by chronic inflammation and fibrotic remodeling of the interstitial tissue. A small fraction of DPLD cases can be genetically defined by mutations in certain genes, with ABCA3 being the gene most commonly affected. However, the pathomechanisms underlying ABCA3-induced DPLD are far from clear. To investigate whether ABCA3 plays a role in cellular cholesterol homeostasis, phospholipids, free cholesterol, and cholesteryl esters were quantified in cells stably expressing ABCA3 using mass spectrometry. Cellular free cholesterol and lipid droplets were visualized by filipin or oil red staining, respectively. Expression of SREBP regulated genes was measured using qPCR. Cell viability was assessed using the XTT assay. We found that wild type ABCA3 reduces cellular free cholesterol levels, induces the SREBP pathway, and renders cells more resistant to loading with exogenous cholesterol. Moreover, ABCA3 mutations found in patients with DPLD interfere with this protective effect of ABCA3, resulting in free cholesterol induced cell death. We conclude that ABCA3 plays a previously unrecognized role in the regulation of cellular cholesterol levels. Accumulation of free cholesterol as a result of a loss of ABCA3 export function represents a novel pathomechanism in ABCA3-induced DPLD. (C) 2015 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTERSTITIAL LUNG-DISEASE; ENDOPLASMIC-RETICULUM STRESS; HIGH-THROUGHPUT QUANTIFICATION; FATAL SURFACTANT DEFICIENCY; PULMONARY SURFACTANT; II CELLS; MESENCHYMAL TRANSITION; INTRACELLULAR VESICLES; RESPIRATORY-FAILURE; TRANSPORTER ABCA3; Diffuse parenchymal lung disease; ABC transporter; ABCA3; Pulmonary surfactant; Cholesterol |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Jul 2019 12:55 |
| Last Modified: | 10 Jul 2019 12:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5286 |
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