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Quintens R.,Catholic University of Leuven | Quintens R.,Radiobiology Unit | Singh S.,University of Texas Southwestern Medical Center | Lemaire K.,Catholic University of Leuven | And 22 more authors.
PLoS ONE | Year: 2013

Oxidative phosphorylation in mitochondria is responsible for 90% of ATP synthesis in most cells. This essential housekeeping function is mediated by nuclear and mitochondrial genes encoding subunits of complex I to V of the respiratory chain. Although complex IV is the best studied of these complexes, the exact function of the striated muscle-specific subunit COX6A2 is still poorly understood. In this study, we show that Cox6a2-deficient mice are protected against high-fat diet-induced obesity, insulin resistance and glucose intolerance. This phenotype results from elevated energy expenditure and a skeletal muscle fiber type switch towards more oxidative fibers. At the molecular level we observe increased formation of reactive oxygen species, constitutive activation of AMP-activated protein kinase, and enhanced expression of uncoupling proteins. Our data indicate that COX6A2 is a regulator of respiratory uncoupling in muscle and we demonstrate that a novel and direct link exists between muscle respiratory chain activity and diet-induced obesity/insulin resistance. © 2013 Quintens et al. Source


Quintens R.,Radiobiology Unit | Moreels M.,Radiobiology Unit | Tabury K.,Radiobiology Unit | MacAeva E.,Radiobiology Unit | And 6 more authors.
European Space Agency, (Special Publication) ESA SP | Year: 2013

In order to better understand and define the biological risks of cosmic radiation, it is important to identify biomarkers for exposure and for predicting individual sensitivity to radiation-induced biological damage. Our study aims at identifying new biomarkers for radiation exposure to low and high linear energy transfer (LET) radiation. We will focus on the use of gene, exon and/or cytokine expression signatures in human peripheral blood mononuclear cells (PBMCs) as biomarkers. These data will be integrated with those from DNA double strand break (DSB) repair kinetics in order to identify biomarkers of individual radiosensitivity. Our preliminary data indicate that gene/exon expression signatures can be used to accurately predict radiation doses of below 0.1 Gy (X-rays). Additionally, specific exon signatures may further enhance the sensitivity of prediction. Also, we found that there is a very strong overlap between gene expression changes in response to high doses (1 Gy) of low (X-ray) and high-LET (C-ions; 50-75 keV/μm) irradiation. However, we also identified genes that only responded to either X-rays or C-ions, suggesting that LET-specific gene signatures may also be identified. © 2013 European Space Agency. Source


Abou-El-Ardat K.,Radiobiology Unit | Abou-El-Ardat K.,Ghent University | Monsieurs P.,Radiobiology Unit | Anastasov N.,Helmholtz Center Munich | And 7 more authors.
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis | Year: 2012

The high doses of radiation received in the wake of the Chernobyl incident and the atomic bombing of Hiroshima and Nagasaki have been linked to the increased appearance of thyroid cancer in the children living in the vicinity of the site. However, the data gathered on the effect of low doses of radiation on the thyroid remain limited. We have examined the genome wide transcriptional response of a culture of TPC-1 human cell line of papillary thyroid carcinoma origin with a RET/PTC1 translocation to various doses (0.0625, 0.5, and 4. Gy) of X-rays and compared it to response of thyroids with a RET/PTC3 translocation and against wild-type mouse thyroids irradiated with the same doses using Affymetrix microarrays. We have found considerable overlap at a high dose of 4. Gy in both RET/PTC-positive systems but no common genes at 62.5. mGy. In addition, the response of RET/PTC-positive system at all doses was distinct from the response of wild-type thyroids with both systems signaling down different pathways. Analysis of the response of microRNAs in TPC-1 cells revealed a radiation-responsive signature of microRNAs in addition to dose-responsive microRNAs. Our results point to the fact that a low dose of X-rays seems to have a significant proliferative effect on normal thyroids. This observation should be studied further as opposed to its effect on RET/PTC-positive thyroids which was subtle, anti-proliferative and system-dependent. © 2011 Elsevier B.V. Source


Moreels M.,Radiobiology Unit | Quintens R.,Radiobiology Unit | De Vos W.,Ghent University | Beck M.,Radiobiology Unit | And 11 more authors.
European Space Agency, (Special Publication) ESA SP | Year: 2013

On Earth, most radiation exposures (medical and natural background) consist of low-linear energy transfer (LET) photons. In space, astronauts are exposed to higher doses and to more varied types of radiation. Cosmic radiation mainly consists of high-energy protons and high-Z and -energy (HZE) particles. These high-LET particles are predicted to account for most of the radiation induced health effects. In this regard, further analysis of the biological effects of HZE particles is essential. In the present study, endothelial cells were irradiated with different doses of nickel ions produced in the synchrotron at GSI (Darmstadt, Germany). After different time points, RNA was extracted for genome-wide analysis and supernatants were collected for multiplex cytokine assay. DNA double strand breaks were detected using γH2AX staining. Our results demonstrated that nickel irradiation induced molecular and cellular changes in human endothelial cells. Further analysis is ongoing to confirm the obtained data and to further explore the biological effects after nickel ion exposure. © 2013 European Space Agency. Source

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