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2010 | 32 | 5 |

Tytuł artykułu

HMG-CoA reductase limits artemisinin biosynthesis and accumulation in Artemisia annua L. plants

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
In vivo modulation of HMG-CoA reductase (HMGR) activity and its impact on artemisinin biosynthesis as well as accumulation were studied through exogenous supply of labeled HMG-CoA (substrate), labeled MVA (the product), and mevinolin (the competitive inhibitor) using twigs of Artemisia annua L. plants collected at the preflowering stage. By increasing the concentration (2–16 µM) of HMG-CoA (3-¹⁴C), incorporation of labeled carbon into artemisinin was enhanced from 7.5 to 17.3 nmol (up to 130%). The incorporation of label (¹⁴C) into MVA and artemisinin was inhibited up to 87.5 and 82.9%, respectively, in the presence of 200 µM mevinolin in incubation medium containing 12 µM HMG-CoA (3-¹⁴C). Interestingly, by increasing the concentration of MVA (2-¹⁴C) from 2 to 18 µM, incorporation of label (¹⁴C) into artemisinin was enhanced from 10.5 to 35 nmol (up to 233%). When HMG-CoA (3-¹⁴C) concentration was increased from 12 to 28 µM in the presence of 150 µM mevinolin, the inhibitions in the incorporation of label (¹⁴C) into MVA and artemisinin were, however, reversed and the labels were found to approach their values in twigs fed with 12 µM HMG-CoA (3-¹⁴C) without mevinolin. In another experiment, 14.2% inhibition in artemisinin accumulation was observed in twigs in the presence of 175 µM fosmidomycin, the competitive inhibitor of 1-deoxy-D-xylulose 5-phosphate reductase (DXR). HMG-CoA reductase activity and artemisinin accumulation were also increased by 18.6 to 24.5% and 30.7 to 38.4%, respectively, after 12 h of treatment, when growth hormones IAA (100 ppm), GA₃ (100 ppm) and IAA + GA₃ (50 + 50 ppm) were sprayed on A. annua plants at the pre-flowering stage. The results obtained in this study, hence, demonstrate that the mevalonate pathway is the major contributor of carbon supply to artemisinin biosynthesis and HMGR limits artemisinin synthesis and its accumulation in A. annua plants.

Słowa kluczowe

Wydawca

-

Rocznik

Tom

32

Numer

5

Opis fizyczny

p.859-866,fig.,ref.

Twórcy

autor
  • Department of Biotechnology, Faculty of Science, Centre for Transgenic Plant Development, Jamia Hamdard, New Delhi 110062, India
autor
  • Department of Biotechnology, Faculty of Science, Centre for Transgenic Plant Development, Jamia Hamdard, New Delhi 110062, India
autor
  • Department of Botany, Faculty of Science, Jamia Hamdard, New Delhi 110062, India
autor
  • Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia
autor
  • Department of Biotechnology, Faculty of Science, Centre for Transgenic Plant Development, Jamia Hamdard, New Delhi 110062, India
autor
  • Department of Biotechnology, Faculty of Science, Centre for Transgenic Plant Development, Jamia Hamdard, New Delhi 110062, India
autor
  • Department of Biochemistry, Faculty of Science, Jamia Hamdard, New Delhi 110062, India
autor
  • Department of Biotechnology, Faculty of Science, Centre for Transgenic Plant Development, Jamia Hamdard, New Delhi 110062, India

Bibliografia

  • Abdin MZ, Israr M, Rehman RU, Jain SK (2003) Artemisinin a novel antimalarial drug: biochemical and molecular approaches for enhanced production. Planta Med 69:289–299
  • Akhila A, Thakur RS, Popli SP (1987) Biosynthesis of artemisinin in Artemisia annua. Phytochem 16:1927–1930
  • Borrmann S, Szlezak N, Faucher JF, Matsiegui PB, Neubauer R, Biner RK, Lell B, Kremsner PG (2001) Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a doubleblind, randomized, placebo-controlled study. J Infec Dis 184:1363–1366
  • Bradford MM (1976) A rapid and sensitive method for quantification of microgram quantities of protein utilizing the principle of protein-dye-binding. Anal Biochem 72:248–254
  • Chappell J, Wolf F, Proulx J, Cuellar R, Saunders C (1995) Is the reaction catalyzed by 3-Hydroxy-3-Methylglutaryl Coenzyme A reductase a rate-limiting step for isoprenoid biosynthesis in plants? Plant Physiol 109:1337–1343
  • Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR (2001) The anti-malarial artesunate is also active against cancer. Int J Oncol 18:767–773
  • Farooqi HA, Shukla A, Sharma S, Khan A (1996) Effect of plant age and GA₃ on artemisinin and essential oil yield in Artemisia annua L. J Herbs Spices Med Plants 4:73–80
  • Fulzele DP, Sipahimalani AT, Heble MR (1995) Tissue culture of Artemisia annua L. plantlets cultures in bioreactor. J Biotechnol 40:139–143
  • Gondet L, Weber T, Maillot-Vernior P, Benveniste P, Bach TJ (1992) Regulatory role of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase in a tobacco mutant that over produce sterols. Biochem Biophys Res Comm 186:888–893
  • Jung M, Schinazi RF (1994) Synthesis and in vitro anti-human immunodeficiency virus acivity of artemisinin (Qinghaousu) related trioxanes. Bioorg Med Chem Lett 4:934–941
  • Kudakasseril GJ, Lukem L, Stabam EJ (1987) Effect of sterol inhibitors on incorporation of 14C-isopentenyl pyrophosphate into artemisinin by a cell free system from Artemisia annua tissue culture and plants. Planta Med 53:280–284
  • Lange BM, Wildung MK, MacCaskill D, Croteau R (1998) A family of transketolases that directs isoprenoid biosynthesis via mevalonate- independent pathway. Proc Nat Acad Sci USA 95:21000–22104
  • Laughlin JC (1994) Effect of agricultural production of artemisinin: a review. Trans Royal Soc Trop Med Hyg 88(Suppl 1):21–22
  • Newton P, White N (1999) Malaria: new development in treatment and prevention. Annual Review Med 50:179–192
  • Rodriguez-Concepcion M, Gruissem M (1999) Arachidonic acid alters tomato HMG expression and fruit growth and induces 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent lycopene accumulation. Plant Physiol 119:41–48
  • Romero MR, Efferth T, Serrano MA, Castano B, Macias R, Briz O, Marin JJ (2005) Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an ‘in vitro’ system. Antiviral Res 68:75–83
  • Russell DW (1985) 3-Hydroxy-3-methylglutaryl-CoA reductases from pea seedlings. Methods Enzymol 110:26–40
  • Russell DW, Davidson H (1982) Regulation of HMG-CoA reductases activity in pea seedlings: contrasting responses to different hormones, and hormone-product interaction, suggest hormonal modulation of activity. Biochem Biophys Res Comm 104:1537–1543
  • Sen R, Bandyopadhyay S, Dutta A, Mandal G, Ganguly S, Saha P (2007) Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania dovani promastigotes. J Med Microbiol 56:1213–1218
  • Singh NP, Lai H (2001) Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. Life Sci 70:49–56
  • Smith T, Weathers PJ, Cheetham RD (1997) Effects of gibberellic acid on hairy root cultures of Artemisia annua: growth and artemisinin production. In Vitro Cell Dev Biol Plant 33:75–79
  • Stermer BA, Bostock MB (1987) Involvement of 3-Hydroxy-3-methylglutaryl-CoA reductase in the regulation of sesquiterpenois phytoalexin synthesis in potato. Plant Physiol 84:404–408
  • Towler MJ, Weathers PJ (2007) Evidence of artemisinin production from IPP stemming from both mevalonate and non-mevalanate pathways. Plant Cell Rep 26:2129–2136
  • Utzinger J, Xiao S, N’Goran EK, Berquist R, Tanner M (2001) The potential of artemether for the control of schistosomiasis. Int J Parasitol 31:1549–1562
  • Van Agtmael MA, Eggetle TA, Van Boxtel CJ (1999) Artemisinin drugs in the treatment of malaria: from medicinal herb to registered medication. Trends Pharmacol Sci 20:199–204
  • Weathers PJ, Bunk G, Macoy MC (2005) The effect of phytohormones on growth and artemisinin production in Artemisia annua hairy roots. J In Vitro Cell Dev Biol Plant 41(1):47–53
  • Whipkey A, Simon JE, Charles DJ, Janick J (1992) In vitro production of artemisinin from Artemisia annua L. Phytother Res 1:15–25
  • Wills RBH, Scurr EV (1975) Mevalonic acid concentrations in fruit and vegetable tissues. Phytochem Reports 14:1643
  • Zhang YS, Ye HC, Liu BY, Wang H, Li GF (2005) Exogenous GA₃ and Flowering Induce the Conversion of Artemisinic Acid to Artemisinin in Artemisia annua Plants. Rus J Plant Physiol 52(1):58–62
  • Zhao SS, Zeng MY (1986) Determination of Qinghaosuin in Artemisia annua L. by high performance liquid chromatography. Chinese J Pharma Anal 6:3–5

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

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