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Modified HMG‐CoA reductase and LDLr regulation is deeply involved in age‐related hypercholesterolemia
Author(s) -
Pallottini Valentina,
Martini Chiara,
Cavallini Gabriella,
Donati Alessio,
Bergamini Ettore,
Notarnicola Maria,
Caruso Maria Gabriella,
Trentalance Anna
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20951
Subject(s) - sterol regulatory element binding protein , ldl receptor , hmg coa reductase , reductase , coenzyme a , cholesterol , endocrinology , medicine , transcription (linguistics) , transcription factor , pcsk9 , biology , receptor , enzyme , chemistry , biochemistry , sterol , lipoprotein , gene , linguistics , philosophy
Abstract During the ageing process in rats hypercholesterolemia occurs in concert with full activation, lowered degradation rate and an unchanged level of the rate limiting cholesterol biosynthesis enzyme, 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMG‐CoAR). The molecular bases of the HMG‐CoAR unchanged level and lowered degradation rate in aged rats is not clear. In fact no data are available during ageing, on transcription and degradation of HMG‐CoAR, so well defined in adult animal. So, aim of this work was to measure mRNA levels of the enzyme and the level of the proteins of the regulatory complex responsible of the cholesterol metabolism. To complete the picture, the level of sterol regulatory element binding proteins (SREBPs), SREBP cleavage activating protein, and insulin‐induced gene has been measured. The levels of other related proteins, whose transcription is SREBP dependent, that is low density lipoprotein receptor (LDLr) and Caveolin 1, have been also measured. The age‐related reduced Insigs levels, joined to a reduced insulin sensitivity, could explain the decreased degradation rate of the HMG‐CoAR and the increased active SREBP‐2. The SREBP‐2 in particular seems to be committed in multiple way to gene transcription. The obtained data represent a good contribution to explain the age‐related hypercholesterolemia. J. Cell. Biochem. 98: 1044–1053, 2006. © 2006 Wiley‐Liss, Inc.