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Dietary and hypothyroid hypercholesterolemia induces hepatic apolipoprotein E expression in the rat: direct role of cholesterol
Author(s) -
Santillo Mariarosaria,
Migliaro Angelo,
Mondola Paolo,
Laezza Chiara,
Damiano Simona,
Stingo Stefania,
Fiorentino Laura,
Andreozzi Adriana,
Vitale Mario,
Bifulco Maurizio
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01604-x
Subject(s) - medicine , endocrinology , apolipoprotein b , forskolin , cholesterol , propylthiouracil , western blot , intracellular , apolipoprotein e , secretion , biology , chemistry , biochemistry , hormone , gene , disease , stimulation
Apolipoprotein E (apo E) exerts a protective effect against atherosclerosis, related to its role in intracellular cholesterol removal and remnants clearance. In this study we investigated the effect of dietary and hypothyroid hypercholesterolemia, induced respectively by a high cholesterol diet and by propylthiouracil, on hepatic apo E expression in Wistar male rats. The Northern and Western blot analysis of hepatic mRNA and protein levels showed a 2–3‐fold increase of apo E in hypercholesterolemic rats compared to controls. The incubation of FAO rat hepatoma cells with 25‐OH cholesterol and mevalonate led to a three‐fold increase of apo E mRNA, demonstrating a direct role of cholesterol on apo E expression. This effect was completely abolished by elevating intracellular cAMP levels with forskolin. Immunoblot and immunofluorescence analysis revealed that 25‐OH cholesterol/mevalonate strongly increased also apo E protein synthesis and secretion in FAO cells. Our data demonstrate that hypercholesterolemia, apart of the cause (diet or hypothyroidism) induces liver apo E expression in the rat and that this effect can be directly related, via cAMP, to cholesterol.

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