20(s)‑ginseonside‑Rg3 modulation of AMPK/FoxO3 signaling to attenuate mitochondrial dysfunction in a dexamethasone‑injured C2C12 myotube‑based model of skeletal atrophy in vitro.

Abstract

Muscle atrophy, a side effect from administration of the anti‑inflammatory medication dexamethasone (DEX), is preventable by concomitant administration of the major monomeric constituent of Panax ginseng C.A. Meyer, 20(S)‑ginsenoside Rg3 (S‑Rg3). Putative S‑Rg3‑associated prevention of DEX‑induced muscle atrophy may involve S‑Rg3 mitigation of DEX‑induced mitochondrial dysfunction. In the present study, MTT assays revealed enhanced cell viability following S‑Rg3 treatment of DEX‑injured C2C12 myotubes. Subsequent PCR and western blotting results demonstrated S‑Rg3‑induced reduction of expression of muscle atrophy F‑box protein (atrogin‑1) and muscle RING‑finger protein‑1, proteins previously linked to muscle atrophy. Additionally, S‑Rg3 treatment of DEX‑injured myotubes led to aggregation of Rg3 monomers in cells and dose‑dependent increases in cellular mitochondrial basal respiratory oxygen consumption rate and intracellular ATP levels compared with their levels in untreated DEX‑injured myotubes. In addition, S‑Rg3 treatment significantly reversed DEX‑induced reductions of expression of key mitochondrial respiratory electron transport chain subunits of protein complexes II, III and V in DEX‑injured myotube cells. Furthermore, S‑Rg3 alleviation of mitochondrial dysfunction associated with DEX‑induced injury of C2C12 myotubes was linked to S‑Rg3‑associated decreases in both forkhead box O3 (FoxO3) protein expression and phosphorylation of AMP‑activated protein kinase (AMPK). Collectively, these results implicate S‑Rg3 modulation of signaling within the AMPK‑FoxO3 pathway as a putative mechanism underlying S‑Rg3 alleviation of DEX‑induced muscle atrophy.

• Authors: Manying Wang, Rui Jiang, Jianzeng Liu, Xiaohao Xu, Guang Sun, Daqing Zhao, Liwei Sun
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 23 Issue 5 (05 2021) ISSN: 1791-3004 [Electronic] Greece
• PMID: 33649814 (Publication Type: Journal Article)

Chemical References

• Electron Transport Chain Complex Proteins
• Forkhead Box Protein O3
• Ginsenosides
• Glucocorticoids
• Muscle Proteins
• Tripartite Motif Proteins
• ginsenoside Rg3
• Dexamethasone
• Adenosine Triphosphate
• Fbxo32 protein, mouse
• SKP Cullin F-Box Protein Ligases
• Trim63 protein, mouse
• Ubiquitin-Protein Ligases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (genetics, metabolism)
• Adenosine Triphosphate (metabolism)
• Animals
• Cell Line
• Cell Survival (drug effects, genetics)
• Dexamethasone (pharmacology)
• Electron Transport Chain Complex Proteins (genetics, metabolism)
• Forkhead Box Protein O3 (genetics, metabolism)
• Gene Expression Regulation (drug effects)
• Ginsenosides (pharmacology)
• Glucocorticoids (pharmacology)
• Mice
• Mitochondria, Muscle (drug effects, metabolism)
• Models, Biological
• Muscle Fibers, Skeletal (cytology, drug effects, metabolism)
• Muscle Proteins (genetics, metabolism)
• Muscular Atrophy (genetics, metabolism, prevention & control)
• SKP Cullin F-Box Protein Ligases (genetics, metabolism)
• Signal Transduction (drug effects, genetics)
• Tripartite Motif Proteins (genetics, metabolism)
• Ubiquitin-Protein Ligases (genetics, metabolism)