Cargando…
The regulatory mechanisms of myogenin expression in doxorubicin-treated rat cardiomyocytes
Doxorubicin, an anthracycline antibiotic, has been used as an anti-neoplastic drug for almost 60 years. However, the mechanism(s) by which anthracyclines cause irreversible myocardial injury remains unclear. In order to delineate possible molecular signals involved in the myocardial toxicity, we ass...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741940/ https://www.ncbi.nlm.nih.gov/pubmed/26452256 |
_version_ | 1782414104836702208 |
---|---|
author | Liu, Shu-Ting Huang, Shih-Ming Ho, Ching-Liang Yen, Li-Chen Huang, Chi-Jung Lin, Wei-Shiang Chan, James Yi-Hsin |
author_facet | Liu, Shu-Ting Huang, Shih-Ming Ho, Ching-Liang Yen, Li-Chen Huang, Chi-Jung Lin, Wei-Shiang Chan, James Yi-Hsin |
author_sort | Liu, Shu-Ting |
collection | PubMed |
description | Doxorubicin, an anthracycline antibiotic, has been used as an anti-neoplastic drug for almost 60 years. However, the mechanism(s) by which anthracyclines cause irreversible myocardial injury remains unclear. In order to delineate possible molecular signals involved in the myocardial toxicity, we assessed candidate genes using mRNA expression profiling in the doxorubicin-treated rat cardiomyocyte H9c2 cell line. In the study, it was confirmed that myogenin, an important transcriptional factor for muscle terminal differentiation, was significantly reduced by doxorubicin in a dose-dependent manner using both RT-PCR and western blot analyses. Also, it was identified that the doxorubicin-reduced myogenin gene level could not be rescued by most cardio-protectants. Furthermore, it was demonstrated how the signaling of the decreased myogenin expression by doxorubicin was altered at the transcriptional, post-transcriptional and translational levels. Based on these findings, a working model was proposed for relieving doxorubicin-associated myocardial toxicity by down-regulating miR-328 expression and increasing voltage-gated calcium channel β1 expression, which is a repressor of myogenin gene regulation. In summary, this study provides several lines of evidence indicating that myogenin is the target for doxorubicin-induced cardio-toxicity and a novel therapeutic strategy for doxorubicin clinical applications based on the regulatory mechanisms of myogenin expression. |
format | Online Article Text |
id | pubmed-4741940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-47419402016-03-17 The regulatory mechanisms of myogenin expression in doxorubicin-treated rat cardiomyocytes Liu, Shu-Ting Huang, Shih-Ming Ho, Ching-Liang Yen, Li-Chen Huang, Chi-Jung Lin, Wei-Shiang Chan, James Yi-Hsin Oncotarget Research Paper Doxorubicin, an anthracycline antibiotic, has been used as an anti-neoplastic drug for almost 60 years. However, the mechanism(s) by which anthracyclines cause irreversible myocardial injury remains unclear. In order to delineate possible molecular signals involved in the myocardial toxicity, we assessed candidate genes using mRNA expression profiling in the doxorubicin-treated rat cardiomyocyte H9c2 cell line. In the study, it was confirmed that myogenin, an important transcriptional factor for muscle terminal differentiation, was significantly reduced by doxorubicin in a dose-dependent manner using both RT-PCR and western blot analyses. Also, it was identified that the doxorubicin-reduced myogenin gene level could not be rescued by most cardio-protectants. Furthermore, it was demonstrated how the signaling of the decreased myogenin expression by doxorubicin was altered at the transcriptional, post-transcriptional and translational levels. Based on these findings, a working model was proposed for relieving doxorubicin-associated myocardial toxicity by down-regulating miR-328 expression and increasing voltage-gated calcium channel β1 expression, which is a repressor of myogenin gene regulation. In summary, this study provides several lines of evidence indicating that myogenin is the target for doxorubicin-induced cardio-toxicity and a novel therapeutic strategy for doxorubicin clinical applications based on the regulatory mechanisms of myogenin expression. Impact Journals LLC 2015-10-07 /pmc/articles/PMC4741940/ /pubmed/26452256 Text en Copyright: © 2015 Liu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Liu, Shu-Ting Huang, Shih-Ming Ho, Ching-Liang Yen, Li-Chen Huang, Chi-Jung Lin, Wei-Shiang Chan, James Yi-Hsin The regulatory mechanisms of myogenin expression in doxorubicin-treated rat cardiomyocytes |
title | The regulatory mechanisms of myogenin expression in doxorubicin-treated rat cardiomyocytes |
title_full | The regulatory mechanisms of myogenin expression in doxorubicin-treated rat cardiomyocytes |
title_fullStr | The regulatory mechanisms of myogenin expression in doxorubicin-treated rat cardiomyocytes |
title_full_unstemmed | The regulatory mechanisms of myogenin expression in doxorubicin-treated rat cardiomyocytes |
title_short | The regulatory mechanisms of myogenin expression in doxorubicin-treated rat cardiomyocytes |
title_sort | regulatory mechanisms of myogenin expression in doxorubicin-treated rat cardiomyocytes |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741940/ https://www.ncbi.nlm.nih.gov/pubmed/26452256 |
work_keys_str_mv | AT liushuting theregulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT huangshihming theregulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT hochingliang theregulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT yenlichen theregulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT huangchijung theregulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT linweishiang theregulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT chanjamesyihsin theregulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT liushuting regulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT huangshihming regulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT hochingliang regulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT yenlichen regulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT huangchijung regulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT linweishiang regulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes AT chanjamesyihsin regulatorymechanismsofmyogeninexpressionindoxorubicintreatedratcardiomyocytes |