Protein Hydrolysate from Spirulina platensis Prevents Dexamethasone-Induced Muscle Atrophy via Akt/Foxo3 Signaling in C2C12 Myotubes

Abstract

Loss of muscle mass is the primary symptom of sarcopenia. Protein intake is recommended to prevent muscle mass loss, and Spirulina platensis, a microalga with high protein content, is a potential protein supplement. Here, we evaluated the differentiation ability of C2C12 cells and the inhibitory effect of Spirulina hydrolysates (SPH) prepared by Collupulin on dexamethasone (DEX)-treated C2C12 cells. SPH contained 578.27 mg/g protein and 92.30 mg/g branched-chain amino acids. SPH increased C2C12 myotube length and diameter, likely owing to increased MyoD1 and Myf5 expression. Inhibition of increased Atrogin-1, MuRF-1, and FoxO3 expression by SPH in DEX-treated C2C12 cells suppressed DEX-induced muscle atrophy. Moreover, SPH inhibited the DEX-induced increase in cytosolic p-Akt protein expression and suppressed the increase in nuclear FoxO3a protein expression, thereby suppressing the increase in the protein expression of the ubiquitin-proteasome-related factors Atrogin-1 and MuRF-1, which are involved in muscle atrophy. SPH suppressed DEX-induced muscle atrophy by activating the Akt/FoxO3a pathway. SPH promoted C2C12 myoblast differentiation into myotubes and inhibited DEX-induced myotube atrophy by suppressing Atrogin-1 and MuRF-1 expression and regulating the FoxO3a transcription factor. Collectively, SPH can be used as a functional food to inhibit muscle atrophy and promote muscle regeneration.

Potential of Food Protein-Derived Bioactive Peptides against Sarcopenia: A Comprehensive Review

“…And, SPH was determined to suppress muscle atrophy in C 2 C 12 cells through up-regulating MyoD1, Myf5, and myogenin and inhibiting Atrogin-1 and MuRF-1 to inhibit the Akt/FoxO3a signaling pathway. 91 Similarly, the antisarcopenic peptide from whey protein was also reported to play a key role via this mechanism. After confirming the antisarcopenic activity of WP-S, Shin et al 67 investigated its underlying molecular mechanism.…”

“…Lee et al reported that the expression levels of Atrogin-1 and MuRF-1 were decreased in C 2 C 12 cells treated with PYP1-5, showing the potential mechanism of PYP1-5 to suppress MPD via UPP. And, SPH was determined to suppress muscle atrophy in C 2 C 12 cells through up-regulating MyoD1, Myf5, and myogenin and inhibiting Atrogin-1 and MuRF-1 to inhibit the Akt/FoxO3a signaling pathway . Similarly, the antisarcopenic peptide from whey protein was also reported to play a key role via this mechanism.…”

“…A previous study was conducted to evaluate the antisarcopenic effect of SPH on dexamethasone-treated C 2 C 12 cells. The results showed that SPH suppressed muscle atrophy mainly through Akt/forkhead box protein (FoxO) 3a signaling pathway, in particular, increasing MyoD1, Myf5, and myogenin as well as inhibiting Atrogin-1, MuRF-1, and FoxO3a . However, there is scanty research on the microbial-derived peptide, which could be of great potential to serve as an antisarcopenic strategy.…”

“…The results showed that SPH suppressed muscle atrophy mainly through Akt/forkhead box protein (FoxO) 3a signaling pathway, in particular, increasing MyoD1, Myf5, and myogenin as well as inhibiting Atrogin-1, MuRF-1, and FoxO3a. 91 However, there is scanty research on the microbial-derived peptide, which could be of great potential to serve as an antisarcopenic strategy. Therefore, more research should be performed in this field in the future.…”

Tetrahedral Framework Nucleic Acids Inhibit Muscular Mitochondria-Mediated Apoptosis and Ameliorate Muscle Atrophy in Sarcopenia

“…MYH7 and Desmin are two key proteins for the sarcomere structure and were significantly increased in the tFNAs treatment groups. To better understand the impact of DEX and tFNAs treatment on myogenic regulating factors, we measured the mRNA expression levels of MyoD and MyoG, the initial transcription factors for the differentiation of myocytes, along with Atrogin and MuRF1 that are related to muscle cell senescence . We detected that the expressions of MyoD and MyoG were both suppressed in the DEX group while Atrogin and MuRF1 were highly expressed.…”