Dietary and hypothyroid hypercholesterolemia induces hepatic apolipoprotein E expression in the rat: direct role of cholesterol

FEBS Letters

Bifulco, Maurizio²  Migliaro, Angelo¹  Vitale, Mario¹  Andreozzi, Adriana¹  Laezza, Chiara¹  Damiano, Simona²  Mondola, Paolo²  Santillo, Mariarosaria²  Stingo, Stefania¹  Fiorentino, Laura¹ 

[1] Centro di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’ del CNR and Dipartimento di Biologia e Patologia Cellulare e Molecolare ‘L. Califano’, Università di Napoli ‘Federico II’, Napoli, Italy;Dipartimento di Neuroscienze e della Comunicazione Interumana-Sezione di Fisiologia, Università di Napoli ‘Federico II’, Napoli, Italy

关键词: Apolipoprotein E;    Hypercholesterolemia;    25-OH Cholesterol;    Cyclic AMP;    FAO hepatoma cell;    apo E;    apolipoprotein E;    MVA;    mevalonate;    PTU;    n-propylthiouracil;    FCS;    fetal calf serum;    PMSF;    phenylmethyl-sulfonylfluoride;    FITC;    fluorescein isothiocyanate;    PBS;    phosphate-buffered saline;   

DOI  :  10.1016/S0014-5793(99)01604-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown