Cellular cholesterol stimulates acute uptake of palmitate by redistribution of fatty acid translocase in type II pneumocytes.
Cholesterol is an abundant lipid of lung surfactant, where its concentration changes relative to phospholipids in response to certain physiological conditions. We investigated the effect of the cellular cholesterol content on uptake and esterification of palmitic acid, and on cellular distribution of fatty acid translocase (FAT/CD36) in alveolar type II cells. Incubation of type II cells with methyl-beta-cyclodextrin-cholesterol complexes increased the cholesterol content of lamellar bodies. The palmitate uptake of type II cells increased in parallel with the cellular cholesterol content. The content of FAT/CD36 increased in membranes and decreased in cytosol in type II cells. The detergent-insoluble fraction (DIGs), isolated from type II cells, was enriched in FAT/CD36 and caveolin-1 after increasing the cellular cholesterol. The total incorporation of labeled palmitic acid into glycerolipids and cholesterol ester (CE) increased by a factor of about 10 when the amount of unbound (14)C-palmitic acid added to type II cells was increased by a factor of about 1000. Under these conditions, a small but significant increase of the palmitate incorporation into PL occurred. Independent from the amount of added palmitate, palmitate incorporation into triacylglycerol decreased and palmitate incorporation into cholesterol ester increased about 40-65-fold. The beta-oxidation of palmitate significantly decreased. We conclude that alveolar type II cells respond to an increase of the cholesterol level with (i) cellular redistribution of FAT/CD36 into DIGs causing enhanced palmitate uptake and increased cholesterol ester-formation, (ii) storage of cholesterol in lamellar bodies, and (iii) induction of the formation of caveolae-like microdomains in the surface membrane, a structure possibly involved in a lamellar body-independent efflux of free cholesterol via the high-density lipoprotein-specific pathway.
Kolleck
Ingrid
I
University Hospital Charité, Department of Neonatology, Humboldt-Universität, D-10098 Berlin, Germany.
Guthmann
Florian
F
Ladhoff
Axel-M
AM
Tandon
Narendra N
NN
Schlame
Michael
M
Rüstow
Bernd
B
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism / Q000502:physiology; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002469:Cell Separation; D002784:Cholesterol / Q000502:physiology*; D004951:Esterification; D015227:Lipid Peroxidation / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008854:Microscopy, Electron; D027361:Organic Anion Transporters / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
D018955:CD36 Antigens; D008562:Membrane Glycoproteins; D027361:Organic Anion Transporters; D019308:Palmitic Acid; D002784:Cholesterol