Altered Oxygen Utilisation in Rat Left Ventricle and Soleus after 14 Days, but not 2 Days, of Environmental Hypoxia
Horscroft, James A
Burgess, Sarah L
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Horscroft, J. A., Burgess, S. L., Hu, Y., & Murray, A. (2015). Altered Oxygen Utilisation in Rat Left Ventricle and Soleus after 14 Days, but not 2 Days, of Environmental Hypoxia. PLoS One, 10 (e0138564)https://doi.org/10.1371/journal.pone.0138564
The effects of environmental hypoxia on cardiac and skeletal muscle metabolism are dependent on the duration and severity of hypoxic exposure, though factors which dictate the nature of the metabolic response to hypoxia are poorly understood. We therefore set out to investigate the time-dependence of metabolic acclimatisation to hypoxia in rat cardiac and skeletal muscle. Rats were housed under normoxic conditions, or exposed to short-term (2 d) or sustained (14 d) hypoxia (10% O_2), after which samples were obtained from the left ventricle of the heart and the soleus for assessment of metabolic regulation and mitochondrial function. Mass-corrected maximal oxidative phosphorylation was 20% lower in the left ventricle following sustained but not short-term hypoxia, though no change was observed in the soleus. After sustained hypoxia, the ratio of octanoyl carnitine- to pyruvate- supported respiration was 11% and 12% lower in the left ventricle and soleus, respectively, whilst hexokinase activity increased by 33% and 2.1-fold in these tissues. mRNA levels of PPARα targets fell after sustained hypoxia in both tissues, but those of PPARα remained unchanged. Despite decreased Ucp3 expression after short-term hypoxia, UCP3 protein levels and mitochondrial coupling remained unchanged. Protein carbonylation was 40% higher after short-term but not sustained hypoxic exposure in the left ventricle, but was unchanged in the soleus at both timepoints. Our findings therefore demonstrate that 14 days, but not 2 days, of hypoxia induces a loss of oxidative capacity in the left ventricle but not the soleus, and a substrate switch away from fatty acid oxidation in both tissues.
JAH received a PhD Studentship from the Biotechnology and Biological Sciences Research Council (Grant number: BB/F016581/1, www.bbsrc.ac.uk (http://www.bbsrc.ac.uk/). SLB received no specific funding for this work. HY received a Departmental Summer Studentship Bursary from Imperial College, London (www.imperial.ac.uk (http://www.imperial.ac.uk/)). AJM received an academic fellowship from the Research Councils UK (www.rcuk.ac.uk (http://www.rcuk.ac.uk/)). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Isaac Newton Trust (1044(y))
External DOI: https://doi.org/10.1371/journal.pone.0138564
This record's URL: https://www.repository.cam.ac.uk/handle/1810/250544
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Licence URL: http://creativecommons.org/licenses/by/4.0/