Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kobayashi, S; Lackey, T; Huang, Y; Bisping, E; Pu, WT; Boxer, LM; Liang, Q.
Transcription factor gata4 regulates cardiac BCL2 gene expression in vitro and in vivo.
FASEB J. 2006; 20(6):800-802
Doi: 10.1096/fj.05-5426fje
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Bisping Egbert Hubertus
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- The transcription factor GATA-4 protects cardiomyocytes against doxorubicin-induced cardiotoxicity. Here, we report the identification of Bcl2 as a direct target gene of GATA4 that may mediate the prosurvival function of GATA4 in cardiomyocytes. Bcl2 transcript and protein levels were reduced by doxorubicin in neonatal rat ventricular cardiomyocytes (NRVC) and in mouse heart as determined by RT-PCR and Western blot analysis. The reduction in Bcl2 was prevented by overexpression of GATA4 in NRVC and in transgenic mouse heart. Also, expression of GATA4 increased baseline Bcl2 levels by 30% in NRVC and 2.7-fold in transgenic heart, indicating the sufficiency of GATA4 to up-regulate Bcl2 gene expression. GATA4 knockdown by siRNA reduced Bcl2 levels by 48% in NRVC, suggesting that GATA4 is required for Bcl2 constitutive gene expression. Transfection of HEK cells with GATA4 plasmids activated Bcl2 promoter and elevated Bcl2 protein levels. Deletion and mutagenesis analysis revealed that a consensus GATA motif at base -266 on the promoter conserved across multiple species is partially responsible for the promoter activity. Electrophoretic mobility shift and chromatin immunoprecipitation assays demonstrate that GATA4 directly bound to this GATA site. Together, these results indicate that GATA4 positively regulates cardiac Bcl2 gene expression in vitro and in vivo.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antibiotics, Antineoplastic - pharmacology
- Cells, Cultured -
- Doxorubicin - pharmacology
- GATA4 Transcription Factor - genetics GATA4 Transcription Factor - metabolism
- Gene Expression Regulation -
- Humans -
- Mice -
- Mice, Transgenic -
- Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism
- Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism
- Rats -
- Rats, Sprague-Dawley -
- bcl-X Protein - metabolism
- Find related publications in this database (Keywords)
- cardiomyocyte
- promoter
- doxorubicin
- cardiotoxicity