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Tissue specificity of mitochondrial adaptations in rats after 4 weeks of normobaric hypoxia

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Abstract

Purpose

Exposure to hypoxia has been suggested to activate multiple adaptive pathways so that muscles are better able to maintain cellular energy homeostasis. However, there is limited research regarding the tissue specificity of this response. The aim of this study was to investigate the influence of tissue specificity on mitochondrial adaptations of rat skeletal and heart muscles after 4 weeks of normobaric hypoxia (FiO2: 0.10).

Methods

Twenty male Wistar rats were randomly assigned to either normobaric hypoxia or normoxia. Mitochondrial respiration was determined in permeabilised muscle fibres from left and right ventricles, soleus and extensorum digitorum longus (EDL). Citrate synthase activity and the relative abundance of proteins associated with mitochondrial biogenesis were also analysed.

Results

After hypoxia exposure, only the soleus and left ventricle (both predominantly oxidative) presented a greater maximal mass-specific respiration (+48 and +25%, p < 0.05) and mitochondrial-specific respiration (+75 and +28%, p < 0.05). Citrate synthase activity was higher in the EDL (0.63 ± 0.08 vs 0.41 ± 0.10 µmol min− 1 µg− 1) and lower in the soleus (0.65 ± 0.17 vs 0.87 ± 0.20 µmol min− 1 µg− 1) in hypoxia with respect to normoxia. There was a lower relative protein abundance of PGC-1α (−25%, p < 0.05) in the right ventricle and a higher relative protein abundance of PGC-1β (+43%, p < 0.05) in the left ventricle of rats exposed to hypoxia, with few differences for protein abundance in the other muscles.

Conclusion

Our results show a muscle-specific response to 4 weeks of normobaric hypoxia. Depending on fibre type, and the presence of ventricular hypertrophy, muscles respond differently to the same degree of environmental hypoxia.

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Data availability

All data generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

EDL:

Extensorum digitorum longus

HIF-1α:

Hypoxia-inducible factor 1α

PGC-1:

Peroxisome proliferator-activated receptor γ coactivator 1

CI to CV:

Complex I to V

HYP:

Hypoxic group

CON:

Control group

LV:

Left heart ventricle

RV:

Right heart ventricle

CS:

Citrate synthase

BSA:

Bovine serum albumin

EA:

Enzymatic activity

RCR:

Respiratory control ratio

SD:

Standard deviation

SE:

Standard error

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Acknowledgements

The authors would like to acknowledge and thank Prof Antonio Zaza, for providing the setup for the study and Riccardo Rizzetto, who cared for the rats. We thank also Dr Simone Porcelli for helping with the mitochondrial respiration analysis.

Funding

This study was funded by Fondo di Ateneo per la Ricerca (FAR)—University of Milano-Bicocca.

Author information

Author notes

  1. Alessandra Ferri and Alice Panariti have contributed equally to this work.

Authors and Affiliations

  1. Institute for Health and Sport, Victoria University, Melbourne, Australia

    Alessandra Ferri & David J. Bishop

  2. School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

    Alessandra Ferri, Alice Panariti, Giuseppe Miserocchi, Gaia Buoli Comani & Ilaria Rivolta

  3. Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy

    Marcella Rocchetti

  4. School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia

    David J. Bishop

Authors
  1. Alessandra Ferri
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  2. Alice Panariti
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  3. Giuseppe Miserocchi
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  4. Marcella Rocchetti
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  5. Gaia Buoli Comani
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  6. Ilaria Rivolta
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  7. David J. Bishop
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Contributions

AF, GM, IR and DJB: conception and design; AF, AP, IR and DJB: collection and assembly of data; MR: provision of study materials; GM: funding support; AF, AP, MR, IR, GBC and DJB: data analysis; AF, AP, GM, IR and DJB: data interpretation; AF, AP, IR and DJB: manuscript writing; AF, AP, GM, MR, IR, GBC and DJB: manuscript approval.

Corresponding authors

Correspondence to Ilaria Rivolta or David J. Bishop.

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Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Communicated by Guido Ferretti.

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Ferri, A., Panariti, A., Miserocchi, G. et al. Tissue specificity of mitochondrial adaptations in rats after 4 weeks of normobaric hypoxia. Eur J Appl Physiol 118, 1641–1652 (2018). https://doi.org/10.1007/s00421-018-3897-9

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  • DOI: https://doi.org/10.1007/s00421-018-3897-9

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