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Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions

  • Authors:
    • Kamil Kobak
    • Monika Kasztura
    • Magdalena Dziegala
    • Jacek Bania
    • Violetta Kapuśniak
    • Waldemar Banasiak
    • Piotr Ponikowski
    • Ewa A. Jankowska
  • View Affiliations / Copyright

    Affiliations: Laboratory for Applied Research on Cardiovascular System, Department of Heart Diseases, Wrocław Medical University, 50‑981 Wrocław, Poland, Department of Food Hygiene and Consumer Health, Wroclaw University of Environmental and Life Sciences, 50‑375 Wroclaw, Poland, Department of Histology and Embryology, Wroclaw University of Environmental and Life Sciences, 50‑375 Wroclaw, Poland, Centre for Heart Diseases, Military Hospital, 50‑981 Wrocław, Poland
    Copyright: © Kobak et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2678-2686
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    Published online on: February 12, 2018
       https://doi.org/10.3892/ijmm.2018.3481
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Abstract

There is clinical evidence that patients with heart failure and concomitant iron deficiency have increased skeletal muscle fatigability and impaired exercise tolerance. It was expected that a skeletal muscle cell line subjected to different degrees of iron availability and/or concomitant hypoxia would demonstrate changes in cell morphology and in the expression of atrophy markers. L6G8C5 rat skeletal myocytes were cultured in normoxia or hypoxia at optimal, reduced or increased iron concentrations. Experiments were performed to evaluate the iron content in cells, cell morphology, and the expression of muscle specific atrophy markers [Atrogin1 and muscle‑specific RING‑finger 1 (MuRF1)], a gene associated with the atrophy/hypertrophy balance [mothers against decapentaplegic homolog 4 (SMAD4)] and a muscle class‑III intermediate filament protein (Desmin) at the mRNA and protein level. Hypoxic treatment caused, as compared to normoxic conditions, an increase in the expression of Atrogin‑1 (P<0.001). Iron‑deficient cells exhibited morphological abnormalities and demonstrated a significant increase in the expression of Atrogin‑1 (P<0.05) and MuRF1 (P<0.05) both in normoxia and hypoxia, which indicated activation of the ubiquitin proteasome pathway associated with protein degradation during muscle atrophy. Depleted iron in cell culture combined with hypoxia also induced a decrease in SMAD4 expression (P<0.001) suggesting modifications leading to atrophy. In contrast, cells cultured in a medium enriched with iron during hypoxia exhibited inverse changes in the expression of atrophy markers (both P<0.05). Desmin was upregulated in cells subjected to both iron depletion and iron excess in normoxia and hypoxia (all P<0.05), but the greatest augmentation of mRNA expression occurred when iron depletion was combined with hypoxia. Notably, in hypoxia, an increased expression of Atrogin‑1 and MuRF1 was associated with an increased expression of transferrin receptor 1, reflecting intracellular iron demand (R=0.76, P<0.01; R=0.86, P<0.01). Hypoxia and iron deficiency when combined exhibited the most detrimental impact on skeletal myocytes, especially in the context of muscle atrophy markers. Conversely, iron supplementation in in vitro conditions acted in a protective manner on these cells.
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Copy and paste a formatted citation
Spandidos Publications style
Kobak K, Kasztura M, Dziegala M, Bania J, Kapuśniak V, Banasiak W, Ponikowski P and Jankowska EA: Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions. Int J Mol Med 41: 2678-2686, 2018.
APA
Kobak, K., Kasztura, M., Dziegala, M., Bania, J., Kapuśniak, V., Banasiak, W. ... Jankowska, E.A. (2018). Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions. International Journal of Molecular Medicine, 41, 2678-2686. https://doi.org/10.3892/ijmm.2018.3481
MLA
Kobak, K., Kasztura, M., Dziegala, M., Bania, J., Kapuśniak, V., Banasiak, W., Ponikowski, P., Jankowska, E. A."Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions". International Journal of Molecular Medicine 41.5 (2018): 2678-2686.
Chicago
Kobak, K., Kasztura, M., Dziegala, M., Bania, J., Kapuśniak, V., Banasiak, W., Ponikowski, P., Jankowska, E. A."Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions". International Journal of Molecular Medicine 41, no. 5 (2018): 2678-2686. https://doi.org/10.3892/ijmm.2018.3481
Copy and paste a formatted citation
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Spandidos Publications style
Kobak K, Kasztura M, Dziegala M, Bania J, Kapuśniak V, Banasiak W, Ponikowski P and Jankowska EA: Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions. Int J Mol Med 41: 2678-2686, 2018.
APA
Kobak, K., Kasztura, M., Dziegala, M., Bania, J., Kapuśniak, V., Banasiak, W. ... Jankowska, E.A. (2018). Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions. International Journal of Molecular Medicine, 41, 2678-2686. https://doi.org/10.3892/ijmm.2018.3481
MLA
Kobak, K., Kasztura, M., Dziegala, M., Bania, J., Kapuśniak, V., Banasiak, W., Ponikowski, P., Jankowska, E. A."Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions". International Journal of Molecular Medicine 41.5 (2018): 2678-2686.
Chicago
Kobak, K., Kasztura, M., Dziegala, M., Bania, J., Kapuśniak, V., Banasiak, W., Ponikowski, P., Jankowska, E. A."Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions". International Journal of Molecular Medicine 41, no. 5 (2018): 2678-2686. https://doi.org/10.3892/ijmm.2018.3481
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