Corticotropin increases the receptor-specific uptake of native low-density lipoprotein (LDL)--but not of oxidized LDL and native or oxidized lipoprotein(a) [Lp(a)]--in HEPG2 cells: no evidence for Lp(a) catabolism via the LDL-receptor.
To understand the interaction of corticotropin (ACTH) and lipid catabolism, we analyzed the influence of ACTH on receptor-mediated lipoprotein uptake and compared the uptake and degradation of human native (N-LDL) and oxidized (Ox-LDL) low-density lipoprotein and native (N-Lp(a)) and oxidized (Ox-Lp(a)) lipoprotein(a) by human hepatoma (HepG2) cells. The receptor affinity of N-LDL, Ox-LDL, N-Lp(a), and Ox-Lp(a) was comparable (Kd, 33, 13, 24, and 13 micrograms/mL medium), whereas the maximum degradative capacity was 10.5-fold higher in N-LDL (Vmax, 1,978 ng/mg cell protein) compared with Ox-LDL (189 ng/mg). In N-LDL, it was 4.5-fold higher than in N-Lp(a) (442 ng/mg) and eightfold higher than in Ox-Lp(a) (246 ng/mg) (P < .05). Addition of ACTH to the cell cultures increased receptor-specific degradation of N-LDL by 44% (2,866 v 1,978 ng/mg, P < .05), whereas changes in Ox-LDL, N-Lp(a), and Ox-Lp(a) showed no significant increase. No differences in uptake specificity were observed with or without ACTH. In addition, a 12-hour preincubation of liver cells with LDL increased Lp(a) uptake by 40% to 50% with (411 v 620 ng/mg) and without (393 v 558 ng/mg) ACTH administration. These data indicate that ACTH elevates receptor-specific uptake of N-LDL, but only to a low extent versus Ox-LDL, N-Lp(a), or Ox-Lp(a). These results support the hypothesis that catabolism of oxidized lipoproteins and Lp(a) through the LDL receptor pathway is only a minor route of lipid metabolism, whereas LDL receptor activity itself can be stimulated by ACTH.
Bartens
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W
Department of Medicine, University of Würzburg, Germany.
Krämer-Guth
A
A
Wanner
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C
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism / Q000493:pharmacokinetics*; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000493:pharmacokinetics*; D009994:Osmolar Concentration; D011973:Receptors, LDL / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D000324:Adrenocorticotropic Hormone