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

Lipids
Susan E Ownby, Raymond J Hohl

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 microM FOH and 125 microM 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 pro...Continue Reading

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Citations

Jul 12, 2014·Sports Medicine·Zsolt Murlasits, Zsolt Radák
Jan 14, 2016·Bioscience, Biotechnology, and Biochemistry·Hsin-Jung HoMichio Komai
Jul 27, 2006·Molecular Reproduction and Development·Emilia RungHåkan Billig
Dec 23, 2009·International Journal of Cancer. Journal International Du Cancer·Ruth ChuSylvia Fong
Jan 6, 2018·Bioscience, Biotechnology, and Biochemistry·Hsin-Jung HoMichio Komai
Feb 22, 2005·International Journal of Cancer. Journal International Du Cancer·Yoshihisa YanoTomohiro Yano
Oct 14, 2005·The Journal of Biological Chemistry·Shubha MurthyRaymond J Hohl
Sep 11, 2004·Lipids·Sarah A Holstein, Raymond J Hohl
Oct 8, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·María T MonteroMiguel A Lasunción
Sep 6, 2013·Experimental Biology and Medicine·Nicolle V FernandesHuanbiao Mo

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