Sodium Butyrate and Valproic Acid as Splicing Restoring Agents in Erythroid Cells of b-Thalassemic Patients
نویسندگان
چکیده مقاله:
Background: b-Thalassemia is a common autosomal recessive disorder in human caused by a defect in b-globin chain synthesis. The most common mutations causing b-Thalassemia have been found to be splicing mutations. Most of which activate aberrant cryptic splicing/sites without complete disruption of normal splicing. IVSI-110 mutation, a common splicing mutation, leads to a 90% reduction of normal b-globin synthesis and lead to blood transfusion dependency in the homozygote forms. However, modulation of splicing can be achieved by activation or suppression of transacting factors such as SR (Serine, Arginine) amino acids and hnRNPs (Heterogeneous ribonucleoprotein particle) through drugs. Objectives: The aim of this study was to investigate the effects of NaBu, isoBu and VPA drugs on restoration of splicing of IVSI-110 b-Thalassemia pre-mRNA in human. Materials and Methods: Primary erythroid cells derived from IVSI-110 b-Thalassemia patients were cultured ex vivo and differentiated in the presence of 0.5 and 1 mM of Na-Butyrate (NaBu), 0.5 mM Isobutyramide (isoBu) and 100 mM Valproic acid (VPA). RT- PCR analysis was used to evaluate the effect of the drugs in correction of normal splicing in b-globin mRNAs. Results: Following treatment with NaBu, isoBu and VPA, the level of normal b-globin mRNA in Primary erythroid cells derived from IVSI-110 b-Thalassemia patients, increased 1.7, 1.5, 1.4 fold, respectively relative to normal b-globin mRNAs. Higher splicing restoration was achieved by NaBu, a histone deacetylase inhibitor, known to upregulate the expression of splicing factors. Conclusion: The results highlighted the therapeutic potential of splicing modulation for genetic diseases caused by splicing mutations.
منابع مشابه
Histone deacetylase inhibitors sodium butyrate and valproic acid delay spontaneous cell death in purified rat retinal ganglion cells
PURPOSE Histone deacetylase inhibitors (HDACi) have neuroprotective effects under various neurodegenerative conditions, e.g., after optic nerve crush (ONC). HDACi-mediated protection of central neurons by increased histone acetylation has not previously been demonstrated in rat retinal ganglion cells (RGCs), although epigenetic changes were shown to be associated with cell death after ONC. We i...
متن کاملChanging Pattern of Histone H3 Methylation following treatment of erythroid progenitors derived from cord blood CD133+ cells with sodium butyrate and thalidomide
Background: Human β-like globin genes regulaon during development from embyonic to adult stage results in generaon of different types of hemoglobin with different funcons. As β-thalassemia and sickle cell disease are disorders of β-globin chain, epigenec drugs such as thalidomide and sodium butyrate which can induce γ-globin gene are considered as a novel therapeuc approach. Drugs effec...
متن کاملInvolvement of RbAp48 in erythroid differentiation of murine erythroleukemia cells induced by sodium butyrate
Normal mammalian terminal erythroid differentiation is a precisely regulated process during which the progenitor cells execute particular programs to form a mature erythrocytic phenotype. In the present study, it was found that RbAp48, a histone-binding protein associated with retinoblastoma protein, was upregulated during terminal erythroid maturation in vivo and in vitro. This indicated that ...
متن کاملTrichostatin A treatment modestly reduced progenitor proliferation, while sodium butyrate and valproic acid resulted in concentration-dependent effects on proliferation and apoptosis. Addition of valproic acid uniquely stimulated CD34 proliferation. Sodium butyrate treatment
haematologica | 2010; 95(7)
متن کاملprevalence of hepatitis B among thalassemic patients in Kerman
A prospective case control study was carried out to evaluate the prevalence of HBsAg in 129 thalassemic patients and 113 children as a control group.ELISA was used for serologic investigations. thalassemic patients were aged 8.5+_3.8 years and children of the control group were aged 7.2+_3.8 years.48.1% of the case group and 36.3% of the control group were female and 51.9% of the case group an...
متن کاملمنابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ذخیره در منابع من قبلا به منابع من ذحیره شده{@ msg_add @}
عنوان ژورنال
دوره 14 شماره 1
صفحات 9- 15
تاریخ انتشار 2016-03-01
با دنبال کردن یک ژورنال هنگامی که شماره جدید این ژورنال منتشر می شود به شما از طریق ایمیل اطلاع داده می شود.
کلمات کلیدی
میزبانی شده توسط پلتفرم ابری doprax.com
copyright © 2015-2023