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Lipids

, Volume 37, Issue 2, pp 185–192 | Cite as

Farnesol and geranylgeraniol: Prevention and reversion of lovastatin-induced effects in NIH3T3 cells

  • Susan E. Ownby
  • Raymond J. HohlEmail author
Articles

Abstract

Mevalonic acid-derived intermediates in the cholesterol biosynthetic pathway have been recognized as being critical to the isoprenylation of a variety of growth-regulating proteins, including those of the RAS superfamily. Treatment of cells with lovastatin, a hydroxymethylglutaryl coenyme A (HMG-CoA) reductase inhibitor, depletes cells of mevalonic acid and thus blocks the isoprenylation of proteins in the RAS superfamily. In NIH3T3 cells pretreated with lovastatin, subsequent addition of farnesol (FOH), but not geranylgeraniol (GGOH), reverses lovastatin’s block of RAS isoprenylation. Neither FOH nor GGOH prevents lovastatin-induced inhibition of RAS isoprenylation when added to cells concurrently with lovastatin. In intact cells, 167 μM FOH and 125 μM GGOH decrease incorporation of [14C]acetate into cholesterol by approximately 50 and 75%, respectively. Results suggest that the radiolabel from either [3H]FOH or [3H]GGOH is incorporated into cholesterol. Co-treatment of cells with lovastatin or mevalonic acid did not significantly alter [3H]FOH or [3H]GGOH incorporation into cholesterol. Lovastatin induces cell rounding; GGOH, but not FOH, both prevents and reverses lovastatin-induced cell rounding. These results provide additional evidence for the existence of a novel “isoprenoid shunt” that differentially utilizes FOH and GGOH as metabolic precursors for isoprenoids that have been depleted by lovastatin treatment.

Keywords

Lovastatin NIH3T3 Cell Farnesol Mevalonic Acid Bovine Calf Serum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

CPSR-1

controlled processes serum replacements-1

FOH

farnesol

GGOH

geranylgeraniol

HMG-CoA

hydroxymethylglutaryl coenzyme A

IgG

immunoglobulin G

LOV

lovastatin

M

modified

Rf

relative mobility

U

unmodified

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Copyright information

© AOCS Press 2001

Authors and Affiliations

  1. 1.Department of Pharmacology, College of MedicineUniversity of IowaIowa City

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