کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5913540 1570404 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Imatinib inhibits the expression of SCO2 and FRATAXIN genes that encode mitochondrial proteins in human Bcr-Abl+ leukemia cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Imatinib inhibits the expression of SCO2 and FRATAXIN genes that encode mitochondrial proteins in human Bcr-Abl+ leukemia cells
چکیده انگلیسی
Imatinib mesylate (IM/Gleevec®), a selective inhibitor of chimeric Bcr-Abl tyrosine kinase, was developed as a first line drug to treat CML and ALL Ph+ patients. Earlier studies have shown that hemin counteracts the IM-induced cell killing in human K-562 CML cells. In this study, we investigated whether IM disrupts the heme-dependent Cytochrome c Oxidase (COX) Biosynthesis and Assembly Pathway (HDCBAP) in Bcr-Abl+ and Bcr-Abl− cells by affecting the expression of key-genes. Cells were exposed to IM and evaluated at time intervals for cell growth, cell death, expression of various genes by RT-PCR analysis as well as Sco2 mature protein levels by western blot analysis and COX enzymatic activity. IM at 1 μM induced extensive cell growth inhibition and cell death as well as marked suppression of the expression of SCO2 and FRATAXIN (FXN) genes in human K-562 and KU-812 Bcr-Abl+ CML cells. IM also reduced the protein level of mature Sco2 mitochondrial protein as well as COX activity in these cell lines. However, treatment of human MOLT-4 Bcr-Abl− cells with 1 μM and even with higher concentrations (4 × 10− 5 M) of IM neither reduced the expression of SCO2 and FXN genes nor suppressed the protein level of mature Sco2 protein and COX activity. Our findings indicate that SCO2 and FXN genes, involved in HDCBAP, are repressed by IM in human Bcr-Abl+ CML cells and may represent novel target sites in leukemia therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Blood Cells, Molecules, and Diseases - Volume 53, Issues 1–2, June–August 2014, Pages 84-90
نویسندگان
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