| Autor: |
Belova SP; Myology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia., Zaripova K; Myology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia., Sharlo K; Myology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia., Kostrominova TY; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine-Northwest, Gary, Indiana., Shenkman BS; Myology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia., Nemirovskaya TL; Myology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2022 Nov 01; Vol. 133 (5), pp. 1149-1163. Date of Electronic Publication: 2022 Oct 13. |
| DOI: |
10.1152/japplphysiol.00415.2022 |
| Abstrakt: |
Current study tested a hypothesis that during skeletal muscle unloading, calcium-dependent signaling pathways, markers of protein synthesis, and expression of E3 ubiquitin ligases can be regulated by metformin. Thirty-two male Wistar rats were randomly assigned into one of four groups: nontreated control (3C), control rats treated with metformin (3CM), 3 days of unloading/hindlimb suspension with placebo (3HS), and 3 days of unloading treated with metformin (3HSM). In soleus muscle of HS group level of phospho-AMP-activated protein kinase (p-AMPK) was decreased by 46% while ATP content was increased by 49% when compared with the control group. There was an increase of the level of phospho-CaMK II (483%) and an upregulation of Calcineurin (CaN), SERCA2a, and Calpain-1 mRNA expression (87%, 41%, and 62%, respectively, P < 0.05) in the HS group relative to the control. HS group also had increased mRNA expression of MuRF1, MAFbx, and ubiquitin (167%, 146%, and 191%, respectively, P < 0.05) when compared with the control soleus muscle. Metformin treatment impeded unloading-induced changes in soleus muscle. In conclusion, metformin treatment during 3 days of soleus muscle unloading: 1 ) prevented the decrease of p-AMPK and increase of ATP content; 2 ) affected regulation of calcium-dependent signaling pathways via level of CaMK II phosphorylation or CaMK II, CaN, SERCA2a, and Calpain-1 mRNA expression; 3 ) attenuated an increase in the expression of critical markers of ubiquitin-proteasome pathways MuRF1, MAFbx, and ubiquitin while not affecting the unloading-induced increase of ULK-1 marker of autophagic/lysosomal pathway. NEW & NOTEWORTHY Current study for the first time tested the hypothesis that during 3 days of soleus muscle unloading, calcium-dependent signaling pathways, markers of protein synthesis, and the expression of E3 ubiquitin ligases can be regulated by metformin. Treatment with metformin during unloading: prevented the decrease of p-AMPK and increase of ATP content, affected regulation of calcium-dependent signaling pathways, and attenuated an increase of critical markers of ubiquitin-proteasome pathways. Nevertheless, metformin treatment has not prevented soleus muscle atrophy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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