The metabolic fate of apolipoprotein A-I-containing lipoproteins internalized into HepG2 cells: resecreted lipoproteins as a potent inducer for cholesterol efflux.
In a chase study using double-radiolabeled apolipoprotein (apo) A-I-containing lipoproteins (14C-labeled cholesteryl ester and 125I-labeled apolipoprotein) with or without apo A-II (Lp A-I/A-II particle and Lp A-I particle), these lipoproteins internalized into HepG2 cells were demonstrated to be time-dependently released into the medium as trichloroacetic acid (TCA)-precipitable fraction. The molar ratio of 14C/125I-radioactivity of TCA-precipitable fraction in the medium was time-dependently decreased. In Sephacryl S-300 HR chromatography of both circulating mature and resecreted apo A-I-containing lipoproteins in the medium after the chase period, a single major protein peak corresponding to that of high density lipoproteins was detected by absorbance at 280 nm. The 14C-radioactivity in apo A-I-containing lipoproteins resecreted from HepG2 cells after 3-h chase was approximately one-fourth of that in circulating mature apo A-I-containing lipoproteins. Cholesterol mass in resecreted apo A-I-containing lipoproteins was three-tenths of that in circulating mature apo A-I-containing lipoproteins. In a cholesterol efflux experiment using macrophage foam cells labeled with [3H]cholesterol, apo A-I-containing lipoproteins resecreted significantly decreased cholesteryl ester radioactivity in macrophage foam cells, as compared with circulating mature apo A-I-containing lipoproteins. There were no remarkable differences in the metabolic fates and cholesterol efflux from macrophage foam cells between Lp A-I and Lp A-I/A-II particles. These results suggest that a part of apo A-I-containing lipoproteins internalized into HepG2 cells may be resecreted in the form of intact lipoproteins with lower cholesterol content, and apo A-I-containing lipoproteins resecreted may be a potent inducer for cholesterol efflux through the processes of reverse cholesterol transport.
Sasahara
T
T
Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan.
Kobori
S
S
Kasho
M
M
Sato
Y
Y
Nishikawa
T
T
Yano
T
T
Takeda
H
H
Shichiri
M
M
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008114:Liver Neoplasms, Experimental; D051379:Mice; D014238:Trichloroacetic Acid / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014238:Trichloroacetic Acid; D002784:Cholesterol