Abstract
We investigated the role of the intrinsic mevalonate cascade in DNA synthesis and cell cycle progression in human peripheral blood mononuclear cells (PBMC) stimulated by phytohemagglutinin (PHA). PHA stimulated the expression of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase mRNA prior to the DNA synthesis (S phase). Pravastatin, an HMG-CoA reductase inhibitor, inhibited DNA synthesis and blocked the entry to S phase in PHA-stimulated PBMC. Mevalonate restored these inhibitory effects. Thus, we examined two major metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP) and farnesyl-pyrophosphate (FPP), using a novel liposome system for uptake into the cells. GGPP, not FPP, restored the pravastatin-induced inhibitions. These data indicated that 1) the intrinsic mevalonate cascade plays critical roles for the entry to S phase and DNA synthesis, and that 2) GGPP is an essential metabolite of mevalonate cascade for cell cycle progression in PBMC stimulated by PHA.
Citations
Apr 12, 2000·Plant Physiology·K OkadaY Kamiya
Sep 19, 2006·FEBS Letters·Tomohiko YoshidaIchiro Tatsuno
Jan 13, 2006·Neurobiology of Disease·S L Cole, R Vassar
Feb 27, 2004·Biochemical and Biophysical Research Communications·Masami FuseIchiro Tatsuno
Mar 16, 2002·European Journal of Biochemistry·Yajaira SuárezMiguel A Lasunción
Jan 17, 2002·Bone·E R Van BeekS E Papapoulos
Feb 3, 2005·Journal of Lipid Research·Carlos FernándezMiguel A Lasunción
Dec 24, 2014·Journal of Dental Research·Y NagaokaK Okabe
Jan 19, 2000·Circulation·D J MaronM F Linton
Jun 15, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Mansoor Mozayan, Tony J F Lee
Oct 3, 1998·The Journal of Biological Chemistry·T TanakaA Hirai
Jul 12, 2019·Scientific Reports·Shou TanakaIchiro Tatsuno
Nov 1, 2017·JCO Clinical Cancer Informatics·Sherif M El-RefaiJeffery C Talbert
Aug 3, 2017·Molecular Medicine Reports·Noriko IshiharaIchiro Tatsuno
Jul 27, 2001·Biochimica Et Biophysica Acta·J Martínez-BotasM A Lasunción
Apr 2, 1999·Biochimica Et Biophysica Acta·T KainouM Kawamukai
Mar 21, 2003·Biochemical and Biophysical Research Communications·Renu WadhwaSunil C Kaul
Jul 30, 2003·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Anu TöyräsJukka Mönkkönen
Apr 18, 2020·Molecular Therapy. Methods & Clinical Development·Ying GongWilfred T V Germeraad