Visit our Expo - Redox and Inflammation signaling 2012

Session XVII : Cell signaling in health and disease Poster XVII, 34
Induction of accumulation of $-globin mRNA in human erythroid cells treated with
psoralens
Ilaria Lampronti1, Nicoletta Bianchi1, Cristina Zuccato1, Francesco Dall’Acqua2,
Margherita Zennaro1, Daniela Vedaldi2, Giampietro Viola2 and Roberto Gambari1,3.
1Department of Biochemistry and Molecular Biology, University of Ferrara,
2Department of Pharmaceutical Sciences, University of Padova, 3GenTech-for-Thal,
Laboratory for the Development of Pharmacological and Pharmacogenomic Therapy of
Thalassemia, Ferrara
The identification of potential therapeutic agents for treatment of hematological diseases,
including #-thalassemia and sickle cell anemia (SCA), can be based on pharmacologicallymediated
regulation of the expression of human $-globin genes, leading to an increase of the
production of fetal hemoglobin (HbF). DNA-binding drugs appear to be of great interest and
represent a promising approach to control gene expression. Among molecules able to interact
with DNA, psoralens and related compounds could be relevant. In this study, we analysed
several linear and angular psoralens. To verify the activity of these furano-cumarins, we
employed two experimental cell systems, the human leukemic K562 cell line for preliminary
studies and the two-phase liquid culture of human erythroid progenitors isolated from normal
donors for further analysis on the most active compounds. Erythroid differentiation was
analysed by benzidine-staining; expression of $-globin genes by quantitative RT-PCR assays
using the Perkin-Elmer 7700 Sequence Detector. The results of our investigation suggest that
angelicin, bergapten and several structurally-related compounds (trimethylangelicin, psoralen,
8-methoxy-psoralen, 4-methyl-psoralen and 5’-methyl-psoralen) are powerful inducers of
erythroid differentiation and $-globin mRNA accumulation both in K562 cells and in human
erythroid precursors. The activity of trimethylangelicin and 8-methoxy-psoralen were found
higher than that displayed by hydroxyurea, commonly used as HbF inducers in $-thalassemia
and SCA patients. Our results could have practical impact, as it is well know that an increase
in $-globin mRNA and fetal hemoglobin production could ameliorate the clinical status of
patients with $-thalassemia and sickle cell anemia.
Work supported by CIB, AVLT (Associazione Veneta per la Lotta alla Talassemia), EU
(Fondi Strutturali Obiettivo 2), Fondazione CARIPARO (Cassa di Risparmio Padova-
Rovigo), ER-SPINNER and PRRIITT.
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