tailieunhanh - Báo cáo khoa học: Transient silencing of Plasmodium falciparum bifunctional glucose-6-phosphate dehydrogenase) 6-phosphogluconolactonase

The bifunctional enzyme glucose-6-phosphate dehydrogenase-6-phospho-gluconolactonase (G6PD-6PGL) found in Plasmodium falciparum has unique structural and functional characteristics restricted to this genus. This study was designed to examine the effects of RNA-mediated PfG6PD-6PGL gene silencing in cultures ofP. falciparumon the expression of para-site antioxidant defense genes at the transcription level. | ềFEBS Journal Transient silencing of Plasmodium falciparum bifunctional glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase Almudena Crooke1 Amalia Diez1 Philip J. Mason2 t and Jose M. Bautista1 1 Department of Biochemistry and Molecular Biology IV Universidad Complutense de Madrid Facultad de Veterinaria Madrid Spain 2 Haematology Department ImperialCollege Schoolof Medicine Hammersmith Hospital Du Cane Road London UK Keywords antisense RNA dsRNA gene silencing glucose-6-phosphate dehydrogenase malaria Plasmodium falciparum Correspondence . Bautista Departamento de Bioquimica y Biologia Molecular IV Universidad Complutense de Madrid Facultad de Veterinaria Ciudad Universitaria 28040 Madrid Spain Fax 34 91 3943824 Tel 34 91 3943823 E-mail jmbau@ Present address Department of Biochemistry and Molecular Biology IV Universidad Complutense de Madrid Escuela de Optica Madrid Spain tPresent address Division of Hematology Department of InternalMedicine Washington University Schoolof Medicine St Louis USA Received 5 August 2005 revised 2 February 2006 accepted 10 February 2006 The bifunctional enzyme glucose-6-phosphate dehydrogenase-6-phospho-gluconolactonase G6PD-6PGL found in Plasmodium falciparum has unique structural and functional characteristics restricted to this genus. This study was designed to examine the effects of RNA-mediated PfG6PD-6PGL gene silencing in cultures of P. falciparum on the expression of parasite antioxidant defense genes at the transcription level. The highest degree of G6PD-6PGL silencing achieved was 86 at the mRNA level with a recovery to almost normal levels within 24 h indicating only transient diminished expression of the PfG6PD-6PGL gene. PfG6PD-6PGL silencing caused arrest of the trophozoite stage and enhanced gametocyte formation. In addition an immediate transcriptional response was shown by thioredoxin reductase suggesting that P. falciparum G6PD-6PGL plays a physiological role in the specific response of the .

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