Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA173421 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To compare expression profiles in the cardiomyocytes with wild type top2b and those with top2b deletion after in vivo treatment of mice with doxorubicin or drug vehicle Doxorubicin is widely used in modern cancer treatments, despite the advent of targeted therapy. However, a dose-dependent cardiotoxicity often limits its clinical use. The prevailing theory hypothesizes that doxorubicin-induced cardiotoxicity is the result of reactive oxygen species (ROS) generation due to redox-cycling of doxorubicin. Here we showed that cardiomyocyte-specific deletion of Topoisomerase II beta (Top2b) markedly reduced DNA double-strand breaks, apoptosis, and functional damages in doxorubicin-treated hearts. To investigate transcriptomic changes after doxorubicin treatment in wild type mouse and mouse with cardiac specific deletion of Top2b, we examined the expression profiles in 4 groups of mice (3/group), ie. wildtype mice with or without doxorubicin treatment and mice with Top2b deletion in the cardiomyocytes with or without doxorubicin treatment. Mice were treated with doxorubicin (25mg/kg, i.p.) or PBS (drug vehicle) for 16 hr or 72 hr. The heart was removed and cardiomyocytes were isolated by using a Langendorff apparatus. After purification, total RNA was extracted from the cardiomyocytes, purified, and used for gene expression analysis. Compared with that in control cardiomyocytes or cardiomyocytes with Top2b deletion, doxorubicin caused a significant expression change in the genome of cardiomyocytes from the wildtype mice. Among the changes, multiple genes encoding mitochondrial structural protein and components of the respiratory chain complexes were down-regulated 72 hr after treatment while multiple genes in the p53 pathway were up-regulated 16 hr after treatment in the wildtype cardiomyocytes. Expression changes were examined in 2 groups of mice (wild type and conditional knockout of top2b in the cardiomyocytes) treated with doxorubicin or PBS for 16 or 72 hours
2012-10-28 | E-GEOD-40289 | biostudies-arrayexpress
Project description:To compare expression profiles in the cardiomyocytes with wild type top2b and those with top2b deletion after in vivo treatment of mice with doxorubicin or drug vehicle Doxorubicin is widely used in modern cancer treatments, despite the advent of targeted therapy. However, a dose-dependent cardiotoxicity often limits its clinical use. The prevailing theory hypothesizes that doxorubicin-induced cardiotoxicity is the result of reactive oxygen species (ROS) generation due to redox-cycling of doxorubicin. Here we showed that cardiomyocyte-specific deletion of Topoisomerase II beta (Top2b) markedly reduced DNA double-strand breaks, apoptosis, and functional damages in doxorubicin-treated hearts. To investigate transcriptomic changes after doxorubicin treatment in wild type mouse and mouse with cardiac specific deletion of Top2b, we examined the expression profiles in 4 groups of mice (3/group), ie. wildtype mice with or without doxorubicin treatment and mice with Top2b deletion in the cardiomyocytes with or without doxorubicin treatment. Mice were treated with doxorubicin (25mg/kg, i.p.) or PBS (drug vehicle) for 16 hr or 72 hr. The heart was removed and cardiomyocytes were isolated by using a Langendorff apparatus. After purification, total RNA was extracted from the cardiomyocytes, purified, and used for gene expression analysis. Compared with that in control cardiomyocytes or cardiomyocytes with Top2b deletion, doxorubicin caused a significant expression change in the genome of cardiomyocytes from the wildtype mice. Among the changes, multiple genes encoding mitochondrial structural protein and components of the respiratory chain complexes were down-regulated 72 hr after treatment while multiple genes in the p53 pathway were up-regulated 16 hr after treatment in the wildtype cardiomyocytes.
2012-10-28 | GSE40289 | GEO
Project description:Anthracyclines are potent chemotherapeutic agents known for their efficacy in treating various cancers via inhibition of topoisomerase II alpha (TOP2A). However, their clinical use is limited due to cardiotoxicity, primarily attributed to off-target inhibition of topoisomerase II beta (TOP2B) in cardiomyocytes. The well-accepted mechanism involves TOP2B inhibition as a key driver of this toxicity. Here, we identify a novel mechanism of anthracycline-induced cardiotoxicity (AIC) involving upregulated TOP2B expression and its direct impact on cardiomyocyte function. Our data show that doxorubicin significantly increased TOP2B protein levels in cardiomyocytes in AIC mouse model. The cardiomyocyte-specific, tamoxifen-inducible TOP2B transgenic mice exhibited pathophysiological features consistent with doxorubicin-induced cardiotoxicity, even without exposure to anthracyclines. Additionally, we discovered that TOP2B binds to SMYD1, a histone methyltransferase critical for muscle cell function. Mutations in SMYD1 are known to cause cardiomyopathy and heart failure in humans, and loss of Smyd1 in mice results in a phenotype resembling AIC. More importantly, TOP2B ASO pretreatment can succussfully prevent the AIC in TOP2B transgenic mice and AIC mouse models. Our findings reveal a novel role for TOP2B in AIC, demonstrating that its upregulation disrupts SMYD1 function in cardiomyocytes, contributing to cardiotoxicity. This study also highlights the therapeutic potential of targeting TOP2B using ASO for preventing AIC in cancer patients, offering new insights into cardioprotective strategies
2026-05-05 | PXD077277 | Pride
Project description:We created mice, which are deficient for Myc specifically in cardiac myocytes by crossing crossed Myc-floxed mice (Mycfl/fl) and MLC-2VCre/+ mice. Serial analysis of earlier stages of gestation revealed that Myc-deficient mice died prematurely at E13.5-14.5. Morphological analyses of E13.5 Myc-null embryos showed normal ventricular size and structure; however, decreased cardiac myocyte proliferation and increased apoptosis was observed. BrdU incorporation rates were also decreased significantly in Myc-null myocardium. Myc-null mice displayed a 3.67-fold increase in apoptotic cardiomyocytes by TUNEL assay. We examined global gene expression using oligonucleotide microarrays. Numerous genes involved in mitochondrial death pathways were dysregulated including Bnip3L and Birc2. Keywords: wildtype vs Myc-null
2007-06-30 | GSE7162 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description: Not available
| S-EPMC11335981 | biostudies-literature
Project description: Not available
| S-EPMC4490682 | biostudies-literature
Project description: Not available
| S-EPMC395764 | biostudies-literature
Project description: Not available
| S-EPMC5321798 | biostudies-literature
Project description: Not available
| S-EPMC5728457 | biostudies-literature