Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MRNA Expression Changes Induced by Myocardial MCU Inhibition

ABSTRACT: Mitochondrial calcium is an important second-messenger controlling fight-or-flight responses in the heart. The molecular identity of MCU (Mitochondrial Calcium Uniporter) was recently discovered allowing us to test this hypothesis in vivo by expressing a myocardial delimited dominant negative form of MCU. We queried mRNA expression changes induced by dominant negative MCU expression in the heart. Neonatal (< 24 h) and 6 week old hearts were harvested from mice expressing the dominant negative MCU construct or wild-type littermates.

ORGANISM(S): Mus musculus

SUBMITTER: Tyler Rasmussen

PROVIDER: E-GEOD-62049 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Inhibition of MCU forces extramitochondrial adaptations governing physiological and pathological stress responses in heart.

Rasmussen Tyler P TP Wu Yuejin Y Joiner Mei-ling A ML Koval Olha M OM Wilson Nicholas R NR Luczak Elizabeth D ED Wang Qinchuan Q Chen Biyi B Gao Zhan Z Zhu Zhiyong Z Wagner Brett A BA Soto Jamie J McCormick Michael L ML Kutschke William W Weiss Robert M RM Yu Liping L Boudreau Ryan L RL Abel E Dale ED Zhan Fenghuang F Spitz Douglas R DR Buettner Garry R GR Song Long-Sheng LS Zingman Leonid V LV Anderson Mark E ME

Proceedings of the National Academy of Sciences of the United States of America 20150707 29

Myocardial mitochondrial Ca(2+) entry enables physiological stress responses but in excess promotes injury and death. However, tissue-specific in vivo systems for testing the role of mitochondrial Ca(2+) are lacking. We developed a mouse model with myocardial delimited transgenic expression of a dominant negative (DN) form of the mitochondrial Ca(2+) uniporter (MCU). DN-MCU mice lack MCU-mediated mitochondrial Ca(2+) entry in myocardium, but, surprisingly, isolated perfused hearts exhibited high ...[more]

PMID: 26153425

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Project description:Understanding toxicity pathways of engineered nanomaterials (ENM) has recently been brought forward as a key step in 21st century ENM risk assessment. Molecular mechanisms linked to phenotypic end points is a step towards the development of toxicity tests based on key events, which may allow for grouping of ENM according to their mechanisms of action. This study identified molecular mechanisms underlying mitochondrial dysfunction in human bronchial epithelial BEAS 2B cells following exposure to one of the most studied multi-walled carbon nanotubes (MWCNTs; Mitsui-7). Asbestos was used as a positive control and a non-carcinogenic glass wool material was included as a negative fibre control. Decreased mitochondrial membrane potential (MMP↓) was observed for MWCNTs at a biologically relevant dose (0.25 μg/cm2) and for asbestos at 2 μg/cm2, but not for glass wool. Extensive temporal transcriptomic and microRNA expression analyses identified a 330-gene signature related to MWCNT- and asbestos-induced MMP↓. Fourty-nine of the MMP↓-associated genes showed highly similar expression patterns over time (six time points) and the majority was found to be regulated by two transcription factors strongly involved in mitochondrial homeostasis, APP and NRF1. In addition, four miRNAs were associated with MMP↓ and one of them, miR-1275, was found to negatively correlate with a large part of the MMP↓-associated genes. Cellular processes such as gluconeogenesis, glucose metabolism, mitochondrial LC-fatty acid β-oxidation and spindle microtubule function were enriched among the MMP↓-associated genes and miRNAs. These results are expected to be useful in the identification of key events in ENM-related toxicity pathways for the development of molecular screening techniques. BEAS 2B cells were exposed to 0.25 and 2 μg/cm2 of MWCNT, asbestos and glass wool (MMVF10) for 1, 4, 6, 12, 24 and 48 hours. Three independent experiments were performed to obtain a total of 3 replicates for each experimental condition. Non-exposed cells for each time point were used as controls. Three samples failed to give adequate quality RNA and a total of 123 samples were hybridized to Affymetrix GeneChip U133 Plus 24-array plates.

Dataset Information

MRNA Expression Changes Induced by Myocardial MCU Inhibition

Publications

Inhibition of MCU forces extramitochondrial adaptations governing physiological and pathological stress responses in heart.

Similar Datasets

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