<abstract xmlns="http://www.w3.org/1999/xhtml"> Background: The alternative splicing of Bcl-x generates the proapoptotic Bcl-xs protein and the antiapoptotic variant Bcl-xl. Previous studies have demonstrated that some chemotherapeutic agents such as emetine, staurosporine, and epigallocatechin gallate (EGCG) in combination with ibuprofen significantly altered the ratio of the Bcl-x variants Bcl-xs/Bcl-xl in various cell lines, suggesting Bcl-x splicing might be affected by the exogenous stimuli.Objective: We investigated the regulative role of imatinib in the alternative pre-mRNA splicing of Bcl-x in K562 cells and the related mechanism.Methods: Cell proliferation was measured using WST assay kit. Cell apoptosis was assayed using an Annexin V-FITC Apoptosis Detection Kit. RT-PCR and western blot assay was used to analyze the mRNA and protein level of alternative splicing of exon 2 in the Bcl-x gene respectively.Results: Imatinib regulated the alternative splicing in the Bcl-x gene in the K562 cells. In addition, we found that hydroxyurea, another agent for the therapy of CML, could enhance the effect of imatinib on the ratio of the Bcl-xl/Bcl-xs. Moreover, the induction of alternative splicing was correlated with protein phosphatase 1 (PP1). Alternatively, pretreatment with calyculin efficiently blocked imatinib-induced alternative splcing in the K562 cells compared with okadaic acid, which showed an important role of PP1 in regulating imatinib-induced splicing.Conclusion: Imatinib regulates the alternative splicing of Bcl-x in K562 cells, which may be associated with the activation of PP1.</abstract>

Background: The alternative splicing of Bcl-x generates the proapoptotic Bcl-xs protein and the antiapoptotic variant Bcl-xl. Previous studies have demonstrated that some chemotherapeutic agents such as emetine, staurosporine, and epigallocatechin gallate (EGCG) in combination with ibuprofen significantly altered the ratio of the Bcl-x variants Bcl-xs/Bcl-xl in various cell lines, suggesting Bcl-x splicing might be affected by the exogenous stimuli.Objective: We investigated the regulative role of imatinib in the alternative pre-mRNA splicing of Bcl-x in K562 cells and the related mechanism.Methods: Cell proliferation was measured using WST assay kit. Cell apoptosis was assayed using an Annexin V-FITC Apoptosis Detection Kit. RT-PCR and western blot assay was used to analyze the mRNA and protein level of alternative splicing of exon 2 in the Bcl-x gene respectively.Results: Imatinib regulated the alternative splicing in the Bcl-x gene in the K562 cells. In addition, we found that hydroxyurea, another agent for the therapy of CML, could enhance the effect of imatinib on the ratio of the Bcl-xl/Bcl-xs. Moreover, the induction of alternative splicing was correlated with protein phosphatase 1 (PP1). Alternatively, pretreatment with calyculin efficiently blocked imatinib-induced alternative splcing in the K562 cells compared with okadaic acid, which showed an important role of PP1 in regulating imatinib-induced splicing.Conclusion: Imatinib regulates the alternative splicing of Bcl-x in K562 cells, which may be associated with the activation of PP1.

Imatinib regulates the alternative pre-mRNA splicing of Bcl-x in K562 cells

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital, Nanchang University,

Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006,

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

{"article-title":"Imatinib regulates the alternative pre-mRNA splicing of Bcl-x in K562 cells"}

Background: The alternative splicing of Bcl-x generates the proapoptotic Bcl-xs protein and the antiapoptotic variant Bcl-xl. Previous studies have...

Imatinib regulates the alternative pre-mRNA splicing of Bcl-x in K562 cells

Article Category: Original article

Publicado en línea: 04 feb 2017

Páginas: 351 - 359

DOI: https://doi.org/10.5372/1905-7415.0603.066

Palabras clave
Alternative splcing, Bcl-x, chronic myelogenous leukemia, imatinib, protein phosphatase 1

© 2017

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Imatinib regulates the alternative pre-mRNA splicing of Bcl-x in K562 cells

Article Category: Original article

Publicado en línea: 04 feb 2017

Páginas: 351 - 359

DOI: https://doi.org/10.5372/1905-7415.0603.066

Palabras claveAlternative splcing, Bcl-x, chronic myelogenous leukemia, imatinib, protein phosphatase 1

© 2017

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Palabras clave
Alternative splcing, Bcl-x, chronic myelogenous leukemia, imatinib, protein phosphatase 1