Small-molecule inhibition of MuRF1 prevents early disuse-induced diaphragmatic dysfunction and atrophy
In clinical conditions such as diaphragm paralysis or mechanical ventilation, disuse-induced diaphragmatic dysfunction (DIDD) is a condition that poses a threat to life. MuRF1 is a key E3-ligase involved in regulating skeletal muscle mass, function, and metabolism, which contributes to the onset of...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
11 February 2023
|
| In: |
International journal of molecular sciences
Year: 2023, Volume: 24, Issue: 4, Pages: 1-17 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms24043637 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms24043637 Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/24/4/3637 
|
| Author Notes: | Fernando Ribeiro, Paula K.N. Alves, Luiz R.G. Bechara, Julio C.B. Ferreira, Siegfried Labeit and Anselmo S. Moriscot |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1900448599 | ||
| 003 | DE-627 | ||
| 005 | 20241205165724.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240829s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms24043637 |2 doi | |
| 035 | |a (DE-627)1900448599 | ||
| 035 | |a (DE-599)KXP1900448599 | ||
| 035 | |a (OCoLC)1475309695 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Ribeiro, Fernando |e VerfasserIn |0 (DE-588)1340501570 |0 (DE-627)1900449250 |4 aut | |
| 245 | 1 | 0 | |a Small-molecule inhibition of MuRF1 prevents early disuse-induced diaphragmatic dysfunction and atrophy |c Fernando Ribeiro, Paula K.N. Alves, Luiz R.G. Bechara, Julio C.B. Ferreira, Siegfried Labeit and Anselmo S. Moriscot |
| 264 | 1 | |c 11 February 2023 | |
| 300 | |b Illustrationen | ||
| 300 | |a 17 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 29.08.2024 | ||
| 520 | |a In clinical conditions such as diaphragm paralysis or mechanical ventilation, disuse-induced diaphragmatic dysfunction (DIDD) is a condition that poses a threat to life. MuRF1 is a key E3-ligase involved in regulating skeletal muscle mass, function, and metabolism, which contributes to the onset of DIDD. We investigated if the small-molecule mediated inhibition of MuRF1 activity (MyoMed-205) protects against early DIDD after 12 h of unilateral diaphragm denervation. Wistar rats were used in this study to determine the compound’s acute toxicity and optimal dosage. For potential DIDD treatment efficacy, diaphragm contractile function and fiber cross-sectional area (CSA) were evaluated. Western blotting investigated potential mechanisms underlying MyoMed-205’s effects in early DIDD. Our results indicate 50 mg/kg bw MyoMed-205 as a suitable dosage to prevent early diaphragmatic contractile dysfunction and atrophy following 12 h of denervation without detectable signs of acute toxicity. Mechanistically, treatment did not affect disuse-induced oxidative stress (4-HNE) increase, whereas phosphorylation of (ser632) HDAC4 was normalized. MyoMed-205 also mitigated FoxO1 activation, inhibited MuRF2, and increased phospho (ser473) Akt protein levels. These findings may suggest that MuRF1 activity significantly contributes to early DIDD pathophysiology. Novel strategies targeting MuRF1 (e.g., MyoMed-205) have potential therapeutic applications for treating early DIDD. | ||
| 650 | 4 | |a atrophy | |
| 650 | 4 | |a contractile dysfunction | |
| 650 | 4 | |a diaphragm | |
| 650 | 4 | |a mechanical unloading | |
| 650 | 4 | |a MuRF1 | |
| 650 | 4 | |a MuRF2 | |
| 700 | 1 | |a Alves, Paula K. N. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bechara, Luiz R. G. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ferreira, Julio C. B. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Labeit, Siegfried |d 1960- |e VerfasserIn |0 (DE-588)1033566837 |0 (DE-627)741562375 |0 (DE-576)381187314 |4 aut | |
| 700 | 1 | |a Moriscot, Anselmo S. |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d Basel : Molecular Diversity Preservation International, 2000 |g 24(2023), 4, Artikel-ID 3637, Seite 1-17 |h Online-Ressource |w (DE-627)316340715 |w (DE-600)2019364-6 |w (DE-576)281194653 |x 1422-0067 |7 nnas |a Small-molecule inhibition of MuRF1 prevents early disuse-induced diaphragmatic dysfunction and atrophy |
| 773 | 1 | 8 | |g volume:24 |g year:2023 |g number:4 |g elocationid:3637 |g pages:1-17 |g extent:17 |a Small-molecule inhibition of MuRF1 prevents early disuse-induced diaphragmatic dysfunction and atrophy |
| 856 | 4 | 0 | |u https://doi.org/10.3390/ijms24043637 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.mdpi.com/1422-0067/24/4/3637 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20240829 | ||
| 993 | |a Article | ||
| 994 | |a 2023 | ||
| 998 | |g 1033566837 |a Labeit, Siegfried |m 1033566837:Labeit, Siegfried |d 60000 |d 61600 |e 60000PL1033566837 |e 61600PL1033566837 |k 0/60000/ |k 1/60000/61600/ |p 5 | ||
| 999 | |a KXP-PPN1900448599 |e 4572543143 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"title":[{"title_sort":"Small-molecule inhibition of MuRF1 prevents early disuse-induced diaphragmatic dysfunction and atrophy","title":"Small-molecule inhibition of MuRF1 prevents early disuse-induced diaphragmatic dysfunction and atrophy"}],"language":["eng"],"person":[{"given":"Fernando","role":"aut","display":"Ribeiro, Fernando","family":"Ribeiro"},{"family":"Alves","display":"Alves, Paula K. N.","given":"Paula K. N.","role":"aut"},{"family":"Bechara","display":"Bechara, Luiz R. G.","given":"Luiz R. G.","role":"aut"},{"display":"Ferreira, Julio C. B.","given":"Julio C. B.","role":"aut","family":"Ferreira"},{"role":"aut","given":"Siegfried","display":"Labeit, Siegfried","family":"Labeit"},{"role":"aut","given":"Anselmo S.","display":"Moriscot, Anselmo S.","family":"Moriscot"}],"name":{"displayForm":["Fernando Ribeiro, Paula K.N. Alves, Luiz R.G. Bechara, Julio C.B. Ferreira, Siegfried Labeit and Anselmo S. Moriscot"]},"id":{"eki":["1900448599"],"doi":["10.3390/ijms24043637"]},"physDesc":[{"noteIll":"Illustrationen","extent":"17 S."}],"note":["Gesehen am 29.08.2024"],"relHost":[{"title":[{"title":"International journal of molecular sciences","title_sort":"International journal of molecular sciences"}],"language":["eng"],"part":{"text":"24(2023), 4, Artikel-ID 3637, Seite 1-17","year":"2023","volume":"24","pages":"1-17","extent":"17","issue":"4"},"pubHistory":["1.2000 -"],"disp":"Small-molecule inhibition of MuRF1 prevents early disuse-induced diaphragmatic dysfunction and atrophyInternational journal of molecular sciences","physDesc":[{"extent":"Online-Ressource"}],"id":{"issn":["1422-0067","1661-6596"],"zdb":["2019364-6"],"eki":["316340715"]},"note":["Gesehen am 17.09.20"],"titleAlt":[{"title":"IJMS"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"recId":"316340715","origin":[{"publisherPlace":"Basel","publisher":"Molecular Diversity Preservation International","dateIssuedDisp":"2000-","dateIssuedKey":"2000"}]}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"recId":"1900448599","origin":[{"dateIssuedDisp":"11 February 2023","dateIssuedKey":"2023"}]} | ||
| SRT | |a RIBEIROFERSMALLMOLEC1120 | ||