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The Effect of β-GPA on the Markers of Anabolic and Catabolic Signaling Pathways in Rat Soleus Muscle at the Initial Stage of Hindlimb Unloading

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract—

Molecular mechanisms initiating the development of atrophic changes in a mammalian postural muscle remain unclear. We have suggested that AMP-activated protein kinase (AMPK) may play an important role in the regulation of anabolic and catabolic signaling pathways in postural muscle at the initial stage of mechanical unloading, since skeletal muscle inactivation can lead to changes in the balance of intramuscular high-energy phosphates. Beta-guanidinopropionic acid (β-GPA) can act as a modulator of the balance of high-energy phosphates, application of which can reduce the content of intracellular high-energy phosphates. The purpose of this study was to assess signaling pathways of protein synthesis and degradation in rat soleus muscle after preliminary treatment with β-GPA followed by 1-day hindlimb unloading. The experiments were performed on male Wistar rats, which were divided into the following groups: (1) vivarium control (C); (2) vivarium control + β-GPA (C + GPA); (3) 1-day hindlimb unloading (HU); and (4) 1-day hindlimb unloading + β-GPA (HU + GPA). β-GPA was administered daily by intraperitoneal injections (400 mg/kg). The content of the key signaling proteins (AMPK, ACC, p70S6K, 4E-BP1, and FOXO3) was determined by gel electrophoresis followed by immunoblotting. The expression of mRNA of ubiquitin ligases (MuRF1 and MAFbx) was evaluated by real-time PCR. A prevention of reduction in phosphorylation of AMPK, ACC and 4E-BP1 and the return to control values of the increased level of p70S6K phosphorylation were observed in the group with 1-day unloading and β-GPA pretreatment. The phosphorylation of AKT and FOXO3, as well as the expression levels of MuRF1 and MAFbx in the HU + GPA group did not differ from the HU group. The obtained data indicate that the AMPK activity may play an important role in the modulation of anabolic mTORC1-signaling in rat soleus muscle at the early stage of simulated microgravity.

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ACKNOWLEDGMENTS

The work was supported by the Russian Science Foundation (project no. 17-75-20 152).

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Authors and Affiliations

  1. Institute of Biomedical Problems, Russian Academy of Sciences, 123007, Moscow, Russia

    N. A. Vilchinskaya, E. P. Mochalova, I. I. Paramonova, S. P. Belova, T. M. Mirzoev & B. S. Shenkman

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  1. N. A. Vilchinskaya
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  2. E. P. Mochalova
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  3. I. I. Paramonova
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  4. S. P. Belova
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  5. T. M. Mirzoev
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  6. B. S. Shenkman
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Correspondence to T. M. Mirzoev.

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The authors state that there is no conflict of interest.

All procedures with animals were approved by the Biomedicine Ethics Committee of the Institute of Biomedical Problems of the Russian Academy of Sciences/Physiology section of the Russian Bioethics Committee (protocol no. 447 of March 28, 2017). All experiments were performed in accordance with the guidelines and recommendations of the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

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Translated by E. Puchkov

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Vilchinskaya, N.A., Mochalova, E.P., Paramonova, I.I. et al. The Effect of β-GPA on the Markers of Anabolic and Catabolic Signaling Pathways in Rat Soleus Muscle at the Initial Stage of Hindlimb Unloading. Biochem. Moscow Suppl. Ser. A 14, 1–6 (2020). https://doi.org/10.1134/S1990747819060102

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  • DOI: https://doi.org/10.1134/S1990747819060102

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