Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading

Skeletal muscle unloading results in atrophy. We hypothesized that pannexin 1 ATP-permeable channel (PANX1) is involved in the response of muscle to unloading. We tested this hypothesis by blocking PANX1, which regulates efflux of ATP from the cytoplasm. Rats were divided into six groups (eight rats...

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Main Authors: Ksenia A. Zaripova, Ekaterina P. Kalashnikova, Svetlana P. Belova, Tatiana Y. Kostrominova, Boris S. Shenkman, Tatiana L. Nemirovskaya
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/19/10444
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author Ksenia A. Zaripova
Ekaterina P. Kalashnikova
Svetlana P. Belova
Tatiana Y. Kostrominova
Boris S. Shenkman
Tatiana L. Nemirovskaya
author_facet Ksenia A. Zaripova
Ekaterina P. Kalashnikova
Svetlana P. Belova
Tatiana Y. Kostrominova
Boris S. Shenkman
Tatiana L. Nemirovskaya
author_sort Ksenia A. Zaripova
collection DOAJ
description Skeletal muscle unloading results in atrophy. We hypothesized that pannexin 1 ATP-permeable channel (PANX1) is involved in the response of muscle to unloading. We tested this hypothesis by blocking PANX1, which regulates efflux of ATP from the cytoplasm. Rats were divided into six groups (eight rats each): non-treated control for 1 and 3 days of the experiments (1C and 3C, respectively), 1 and 3 days of hindlimb suspension (HS) with placebo (1H and 3H, respectively), and 1 and 3 days of HS with PANX1 inhibitor probenecid (PRB; 1HP and 3HP, respectively). When compared with 3C group there was a significant increase in ATP in soleus muscle of 3H and 3HP groups (32 and 51%, respectively, <i>p</i> < 0.05). When compared with 3H group, 3HP group had: (1) lower mRNA expression of E3 ligases MuRF1 and MAFbx (by 50 and 38% respectively, <i>p</i> < 0.05) and MYOG (by 34%, <i>p</i> < 0.05); (2) higher phosphorylation of p70S6k and p90RSK (by 51 and 35% respectively, <i>p</i> < 0.05); (3) lower levels of phosphorylated eEF2 (by 157%, <i>p</i> < 0.05); (4) higher level of phosphorylated GSK3β (by 189%, <i>p</i> < 0.05). In conclusion, PANX1 ATP-permeable channels are involved in the regulation of muscle atrophic processes by modulating expression of E3 ligases, and protein translation and elongation processes during unloading.
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spelling doaj.art-1fc17c16a5c948eeb4223a5d420c6eac2023-11-22T16:09:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191044410.3390/ijms221910444Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle UnloadingKsenia A. Zaripova0Ekaterina P. Kalashnikova1Svetlana P. Belova2Tatiana Y. Kostrominova3Boris S. Shenkman4Tatiana L. Nemirovskaya5Institute of Biomedical Problems, RAS, 123007 Moscow, RussiaInstitute of Biomedical Problems, RAS, 123007 Moscow, RussiaInstitute of Biomedical Problems, RAS, 123007 Moscow, RussiaDepartment of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine-Northwest, Gary, IN 46408, USAInstitute of Biomedical Problems, RAS, 123007 Moscow, RussiaInstitute of Biomedical Problems, RAS, 123007 Moscow, RussiaSkeletal muscle unloading results in atrophy. We hypothesized that pannexin 1 ATP-permeable channel (PANX1) is involved in the response of muscle to unloading. We tested this hypothesis by blocking PANX1, which regulates efflux of ATP from the cytoplasm. Rats were divided into six groups (eight rats each): non-treated control for 1 and 3 days of the experiments (1C and 3C, respectively), 1 and 3 days of hindlimb suspension (HS) with placebo (1H and 3H, respectively), and 1 and 3 days of HS with PANX1 inhibitor probenecid (PRB; 1HP and 3HP, respectively). When compared with 3C group there was a significant increase in ATP in soleus muscle of 3H and 3HP groups (32 and 51%, respectively, <i>p</i> < 0.05). When compared with 3H group, 3HP group had: (1) lower mRNA expression of E3 ligases MuRF1 and MAFbx (by 50 and 38% respectively, <i>p</i> < 0.05) and MYOG (by 34%, <i>p</i> < 0.05); (2) higher phosphorylation of p70S6k and p90RSK (by 51 and 35% respectively, <i>p</i> < 0.05); (3) lower levels of phosphorylated eEF2 (by 157%, <i>p</i> < 0.05); (4) higher level of phosphorylated GSK3β (by 189%, <i>p</i> < 0.05). In conclusion, PANX1 ATP-permeable channels are involved in the regulation of muscle atrophic processes by modulating expression of E3 ligases, and protein translation and elongation processes during unloading.https://www.mdpi.com/1422-0067/22/19/10444muscle unloadingpannexin channel 1MuRF1MAFbx
spellingShingle Ksenia A. Zaripova
Ekaterina P. Kalashnikova
Svetlana P. Belova
Tatiana Y. Kostrominova
Boris S. Shenkman
Tatiana L. Nemirovskaya
Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading
International Journal of Molecular Sciences
muscle unloading
pannexin channel 1
MuRF1
MAFbx
title Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading
title_full Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading
title_fullStr Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading
title_full_unstemmed Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading
title_short Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading
title_sort role of pannexin 1 atp permeable channels in the regulation of signaling pathways during skeletal muscle unloading
topic muscle unloading
pannexin channel 1
MuRF1
MAFbx
url https://www.mdpi.com/1422-0067/22/19/10444
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