Lipids

, 44:907 | Cite as

Regulation of HMGCoA Reductase Activity by Policosanol and Octacosadienol, a New Synthetic Analogue of Octacosanol

  • Simonetta Oliaro-Bosso
  • Emanuela Calcio Gaudino
  • Stefano Mantegna
  • Enrico Giraudo
  • Claudia Meda
  • Franca Viola
  • Giancarlo Cravotto
Original Article

Abstract

Octacosa-10,19-dien-1-ol is a newly synthesized long-chain alcohol, an unsaturated analogue of 1-octacosanol, the major component of policosanol, the purified natural mixture of different higher aliphatic alcohols obtained from sugarcane wax. Our efficient synthetic protocol (five steps with 50% overall yield) is well suited for gram scale preparations and a rapid generation of analogues with different degrees of unsaturation. Beneficial effects of policosanol in the prevention of atherosclerosis and thromboembolic disorders have been reported and related to the inhibition of sterol biosynthesis possibly by the regulation of the activity of HMGCoA reductase mediated by AMP-dependent kinase AMPK. We have compared the effect of octacosadienol and policosanol on the regulation of HMGCoA reductase in HUVEC and HepG2 human hepatoma cells. Octacosadienol was as effective as policosanol in inhibiting the upregulation of HMGCoA reductase, in inducing the phosphorylation of AMPK and in downregulating the HMGCoA reductase mRNA.

Keywords

Long-chain alcohols synthesis Octacosadienol Octacosanol HMGCoA reductase Policosanol AMPK phosphorylation 

Abbreviations

AMPK

AMP-activated protein kinase

DMEM

Dulbecco-modified Eagle medium

EDTA

Ethylenediaminetetraacetic acid

EGTA

Ethylene glycol tetraacetic acid

HMGR

HydroxyMethylGlutaryl-Coenzyme A reductase

HUVEC

Human endothelial cells from umbilical cord veins

LDL

Low density lipoproteins

LDM

Lipid-depleted medium

PBS

Phosphate-buffered saline

RT-PCR

Real time-polymerase chain reaction

SDS

Sodium dodecyl sulfate

THF

Tetrahydrofurane

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Copyright information

© AOCS 2009

Authors and Affiliations

  • Simonetta Oliaro-Bosso
    • 1
  • Emanuela Calcio Gaudino
    • 1
  • Stefano Mantegna
    • 1
  • Enrico Giraudo
    • 2
  • Claudia Meda
    • 2
  • Franca Viola
    • 1
  • Giancarlo Cravotto
    • 1
  1. 1.Dipartimento di Scienza e Tecnologia del FarmacoUniversity of TorinoTorinoItaly
  2. 2.Department of Oncological Sciences, Institute for Cancer Research and TreatmentUniversity of Torino School of MedicineCandioloItaly

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