Modified HMG-CoA reductase and LDLr regulation is deeply involved in age-related hypercholesterolemia

Valentina Pallottini, Chiara Martini, Gabriella Cavallini, Alessio Donati, Ettore Bergamini, Maria Notarnicola, Maria Gabriella Caruso, Anna Trentalance

Research output: Contribution to journalArticle

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 (HMC-CoAR). The molecular bases of the HMC-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 HMC-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 lipoprotei n receptor (LDLr) and Caveolin 1, have been also measured. The age-related reduced lnsigs levels, joined to a reduced insulin sensitivity, could explain the decreased degradation rate of the HMC-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.

Original languageEnglish
Pages (from-to)1044-1053
Number of pages10
JournalJournal of Cellular Biochemistry
Volume98
Issue number5
DOIs
Publication statusPublished - Aug 1 2006

Keywords

  • Ageing
  • Cholesterol
  • HMG-CoA reductase
  • Insig
  • LDLr
  • Rat liver
  • SCAP
  • SREBPs

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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