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Article

The Role of Glycogen Synthase Kinase-3 in the Regulation of Ribosome Biogenesis in Rat Soleus Muscle under Disuse Conditions

Myology Laboratory, Institute of Biomedical Problems RAS, 123007 Moscow, Russia
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Author to whom correspondence should be addressed.
Academic Editor: Rasmus Kjøbsted
Int. J. Mol. Sci. 2022, 23(5), 2751; https://doi.org/10.3390/ijms23052751
Received: 29 December 2021 / Revised: 16 February 2022 / Accepted: 28 February 2022 / Published: 2 March 2022
(This article belongs to the Special Issue Advances in Skeletal Muscle Function and Metabolism)
It is well-established that prolonged exposure to real or simulated microgravity/disuse conditions results in a significant reduction in the rate of muscle protein synthesis (PS) and loss of muscle mass. Muscle protein synthesis is largely dependent upon translational capacity (ribosome content), the regulation of which is poorly explored under conditions of mechanical unloading. Glycogen synthase kinase-3 (GSK-3) (a negative regulator of PS) is known to be activated in rat soleus muscle under unloading conditions. We hypothesized that inhibition of GSK-3 activity under disuse conditions (hindlimb suspension, HS) would reduce disuse-induced downregulation of ribosome biogenesis in rat soleus muscle. Wistar rats were randomly divided into four groups: (1) vivarium control (C), (2) vivarium control + daily injections (4 mg/kg) of AR-A014418 (GSK-3 inhibitor) for 7 days, (3) 7-day HS, (4) 7-day HS + daily injections (4 mg/kg) of AR-A014418. GSK-3beta and glycogen synthase 1 (GS-1) phosphorylation levels were measured by Western-blotting. The key markers of ribosome biogenesis were assessed via agarose gel-electrophoresis and RT-PCR. The rate of muscle PS was assessed by puromycin-based SUnSET method. As expected, 7-day HS resulted in a significant decrease in the inhibitory Ser9 GSK-3beta phosphorylation and an increase in GS-1 (Ser641) phosphorylation compared to the C group. Treatment of rats with GSK-3 inhibitor prevented HS-induced increase in GS1 (Ser641) phosphorylation, which was indicative of GSK-3 inhibition. Administration of GSK-3 inhibitor partly attenuated disuse-induced downregulation of c-Myc expression as well as decreases in the levels of 45S pre-rRNA and 18S + 28S rRNAs. These AR-A014418-induced alterations in the markers of ribosome biogenesis were paralleled with partial prevention of a decrease in the rate of muscle PS. Thus, inhibition of GSK-3 during 7-day HS is able to partially attenuate the reductions in translational capacity and the rate of PS in rat soleus muscle. View Full-Text
Keywords: soleus muscle; hindlimb unloading; simulated microgravity; GSK-3; ribosome biogenesis; muscle protein synthesis; c-Myc; 18S rRNA; 28S rRNA soleus muscle; hindlimb unloading; simulated microgravity; GSK-3; ribosome biogenesis; muscle protein synthesis; c-Myc; 18S rRNA; 28S rRNA
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MDPI and ACS Style

Rozhkov, S.V.; Sharlo, K.A.; Shenkman, B.S.; Mirzoev, T.M. The Role of Glycogen Synthase Kinase-3 in the Regulation of Ribosome Biogenesis in Rat Soleus Muscle under Disuse Conditions. Int. J. Mol. Sci. 2022, 23, 2751. https://doi.org/10.3390/ijms23052751

AMA Style

Rozhkov SV, Sharlo KA, Shenkman BS, Mirzoev TM. The Role of Glycogen Synthase Kinase-3 in the Regulation of Ribosome Biogenesis in Rat Soleus Muscle under Disuse Conditions. International Journal of Molecular Sciences. 2022; 23(5):2751. https://doi.org/10.3390/ijms23052751

Chicago/Turabian Style

Rozhkov, Sergey V., Kristina A. Sharlo, Boris S. Shenkman, and Timur M. Mirzoev. 2022. "The Role of Glycogen Synthase Kinase-3 in the Regulation of Ribosome Biogenesis in Rat Soleus Muscle under Disuse Conditions" International Journal of Molecular Sciences 23, no. 5: 2751. https://doi.org/10.3390/ijms23052751

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