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

Susan E. Ownby, Raymond Hohl

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 coenzyme 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 radio-label 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.

Original languageEnglish (US)
Pages (from-to)185-192
Number of pages8
JournalLipids
Volume37
Issue number2
DOIs
StatePublished - Jan 1 2002

Fingerprint

Farnesol
Lovastatin
Prenylation
Mevalonic Acid
Cholesterol
Terpenes
Protein Prenylation
Cells
geranylgeraniol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Biosynthetic Pathways
Coenzyme A
Radio
Labels
Oxidoreductases
Proteins
Acetates

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Organic Chemistry
  • Cell Biology

Cite this

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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 coenzyme 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 radio-label 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.",
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Farnesol and geranylgeraniol : Prevention and reversion of lovastatin-induced effects in NIH3T3 cells. / Ownby, Susan E.; Hohl, Raymond.

In: Lipids, Vol. 37, No. 2, 01.01.2002, p. 185-192.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Farnesol and geranylgeraniol

T2 - Prevention and reversion of lovastatin-induced effects in NIH3T3 cells

AU - Ownby, Susan E.

AU - Hohl, Raymond

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