Spatheliachromen mitigates methylglyoxal-induced myotube atrophy by activating Nrf2, inhibiting ubiquitin-mediated protein degradation, and restoring mitochondrial function
Background: Methylglyoxal (MGO) is a potent precursor of glycative stress that leads to oxidative stress and muscle atrophy in diabetes. Spatheliachromen (FPATM-20), derived from Ficus pumila var. awkeotsang, exhibited potential antioxidant activity. Purpose: This study aimed to evaluate the potenti...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2024
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| Sorozat: | EUROPEAN JOURNAL OF PHARMACOLOGY
984 |
| Tárgyszavak: | |
| doi: | 10.1016/j.ejphar.2024.177070 |
| mtmt: | 35590836 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/37029 |
| LEADER | 03036nab a2200313 i 4500 | ||
|---|---|---|---|
| 001 | publ37029 | ||
| 005 | 20250620100512.0 | ||
| 008 | 250620s2024 hu o 000 eng d | ||
| 022 | |a 0014-2999 | ||
| 024 | 7 | |a 10.1016/j.ejphar.2024.177070 |2 doi | |
| 024 | 7 | |a 35590836 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chuang Y.-F. | |
| 245 | 1 | 0 | |a Spatheliachromen mitigates methylglyoxal-induced myotube atrophy by activating Nrf2, inhibiting ubiquitin-mediated protein degradation, and restoring mitochondrial function |h [elektronikus dokumentum] / |c Chuang Y.-F. |
| 260 | |c 2024 | ||
| 300 | |a 15 | ||
| 490 | 0 | |a EUROPEAN JOURNAL OF PHARMACOLOGY |v 984 | |
| 520 | 3 | |a Background: Methylglyoxal (MGO) is a potent precursor of glycative stress that leads to oxidative stress and muscle atrophy in diabetes. Spatheliachromen (FPATM-20), derived from Ficus pumila var. awkeotsang, exhibited potential antioxidant activity. Purpose: This study aimed to evaluate the potential impact and underlying mechanisms of FPATM-20 on MGO-induced myotube atrophy and mitochondrial dysfunction in mouse skeletal C2C12 myotubes. Methods: Atrophic and antioxidant factors were evaluated using immunofluorescence, enzyme-linked immunosorbent assay, and western blotting. Mitochondrial function was assessed using the ATP assay and Seahorse Cell Mito Stress Test. The glycogen content was determined using periodic acid-Schiff staining. Molecular docking was performed to determine the interaction between FPATM-20 and Keap1. Results: In myotubes treated with MGO, FPATM-20 activated the Nrf2 pathway, reduced ROS levels, enhanced antioxidant defense, and increased glycogen content. FPATM-20 improved myotube viability and size, upregulated myosin heavy chain (MyHC) expression, modulated ubiquitin-proteasome molecules (nuclear FoxO3a, atrogin-1, MuRF-1, and p62/SQSTM1), and inhibited apoptosis (Bax/Bcl-2 ratio and cleaved caspase 3). Moreover, FPATM-20 restored mitochondrial function, including mitochondrial membrane potential, mitochondrial oxygen consumption rate, and mitochondrial biogenesis pathway (nuclear PGC-1α/TFAM/FNDC5). The inhibition of Nrf2 with ML385 reversed the effects of FPATM-20 on MGO. Furthermore, molecular docking confirmed the binding of FPATM-20 to Keap1, a suppressor of Nrf2, showing the crucial role of Nrf2 in protective effects. Conclusions: FPATM-20 protects myotubes from MGO toxicity by activating the Nrf2 antioxidant defense, reducing protein degradation and apoptosis, and enhancing mitochondrial function. Thus, FPATM-20 may be a novel agent for preventing skeletal muscle atrophy. © 2024 | |
| 650 | 4 | |a Általános orvostudomány | |
| 700 | 0 | 1 | |a Cheng L. |e aut |
| 700 | 0 | 1 | |a Chang W.-H. |e aut |
| 700 | 0 | 1 | |a Yu Szu-Yin |e aut |
| 700 | 0 | 1 | |a Hsu H.-T. |e aut |
| 700 | 0 | 1 | |a An L.-M. |e aut |
| 700 | 0 | 1 | |a Yen C.-H. |e aut |
| 700 | 0 | 1 | |a Chang F.-R. |e aut |
| 700 | 0 | 1 | |a Lo Y.-C. |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/37029/1/1-s2.0-S001429992400760X-main.pdf |z Dokumentum-elérés |