title: Metabolism of farnesyl diphosphate in tobacco BY-2 cells treated with squalestatin.
abstract: Plant isoprenoids represent a large group of compounds with a wide range of physiological functions. In the cytosol, isoprenoids are synthesized via the classical acetate/mevalonate pathway. In this pathway, farnesyl diphosphate (FPP) occupies a central position, from which isoprene units are dispatched to the different classes of isoprenoids, with sterols as the major end products. The present work deals with effects of squalestatin (SQ) on the metabolism of FPP in proliferating and synchronized cultured tobacco cv. Bright Yellow-2 cells. SQ is a potent inhibitor of squalene synthase (SQS), the first committed enzyme in the sterol pathway. At nanomolar concentrations, SQ severely impaired cell growth and sterol biosynthesis, as attested by the rapid decrease in SQS activity. At the same time, it triggered a several-fold increase in both the enzymic activity and mRNA levels of 3-hydroxy-3-methylglutaryl CoA reductase. When SQ was added to cells synchronized by aphidicolin treatment, it was found to block the cell cycle at the end of G(1) phase, but no cell death was induced. Tobacco cells were also fed exogenous tritiated trans-trans farnesol, the allylic alcohol derived from FPP, in the presence and absence of SQ. Evidence is presented that this compound was incorporated into sterols and ubiquinone Q(10). In the presence of SQ, the sterol pathway was inhibited, but no increase in the radioactivity of ubiquinone was observed, suggesting that this metabolic channel was already saturated under normal conditions.
authors.affiliation: Institut de Biologie Moléculaire des Plantes du CNRS (FRE 2161), Département des Isoprénoïdes, 28 rue Goethe, 67083 Strasbourg, France. ma.hartmann@ibmp-ulp.u-strasbg.fr
authors.forename: M A
authors.initials: MA
authors.lastname: Hartmann
authors.forename: L
authors.initials: L
authors.lastname: Wentzinger
authors.forename: A
authors.initials: A
authors.lastname: Hemmerlin
authors.forename: T J
authors.initials: TJ
authors.lastname: Bach
mesh_terms: D016590:Aphidicolin / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003067:Coenzymes; D005204:Farnesol / Q000378:metabolism; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D016193:G1 Phase; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010947:Plants, Toxic; D011106:Polyisoprenyl Phosphates / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D012717:Sesquiterpenes; D019346:Sodium Acetate / Q000378:metabolism; D013261:Sterols / Q000096:biosynthesis; D014026:Nicotiana / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014233:Tricarboxylic Acids / Q000494:pharmacology*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000096:biosynthesis
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002250:Carbon Radioisotopes; D003067:Coenzymes; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D013261:Sterols; D014233:Tricarboxylic Acids; C075117:squalestatin 1; D014451:Ubiquinone; D016590:Aphidicolin; D019346:Sodium Acetate; D005204:Farnesol; C004808:farnesyl pyrophosphate; D006903:Hydroxymethylglutaryl CoA Reductases; D013186:Farnesyl-Diphosphate Farnesyltransferase; C024989:coenzyme Q10