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. 2024 Mar 18;13(6):919.
doi: 10.3390/foods13060919.

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways

Mohammad Sadiq Amin  1   2   3 , Binbin Yu  1   2 , Dongjing Wu  1   2 , Yujia Lu  4 , Wei Wu  5 , Jing Wang  6 , Yuhao Zhang  1   2 , Yu Fu  1   2
Affiliations

Zein-Derived Peptides from Corn Promote the Proliferation of C2C12 Myoblasts via Crosstalk of mTORC1 and mTORC2 Signaling Pathways

Mohammad Sadiq Amin et al. Foods. .

Abstract

Dietary protein supplementation has emerged as a promising strategy in combating sarcopenia. Furthermore, searching for alternatives of animal proteins has been a hot topic. The present study aimed to investigate the effects of zein peptides on C2C12 myoblasts and explore their potential molecular mechanisms. The proliferative, cell cycle, and anti-apoptotic activities of zein peptides were evaluated. Peptidomics analysis and transcriptome sequencing were employed to explore the structure-activity relationship and underlying molecular mechanisms. The results indicated that zein peptides (0.05-0.2 mg/mL) exerted a significant proliferation-promoting impact on C2C12 cells, via increasing cell viability by 33.37 to 42.39%. Furthermore, zein peptides significantly increased S phase proportion and decreased the apoptosis rate from 34.08% (model group) to 28.96% in C2C12 cells. In addition, zein peptides exhibited a pronounced anti-apoptotic effect on C2C12 cells. Zein peptides are abundant in branch-chain amino acids, especially leucine. Transcriptomics analysis revealed that zein peptides can promote proliferation, accelerate cell cycle, and improve protein synthesis of muscle cells through mTORC1 and mTORC2 signaling pathways.

Keywords: anti-apoptotic; cell cycle; cell proliferation; mTOR pathway; molecular mechanism; myoblast; zein peptides.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Effects of zein peptides on proliferation of C2C12 cells. Different letters above the columns indicate that the means of different groups were significantly different at 24 or 48 h (p < 0.05).
Figure 2
Figure 2
Effects of zein peptides on cell cycle of C2C12 cells analyzed using flow cytometry and the percentage of cell population distribution in G0/G1, S, or G2/M. Different letters above the columns indicate that the means of different groups were significantly different (p < 0.05).
Figure 3
Figure 3
Effects of zein peptides on the apoptosis of C2C12 cells. Q1 represents necrotic cells; Q2, late apoptotic cells; Q3, live cells; Q4, early apoptotic cells; and the apoptosis rate is the ratio of early and late apoptotic cells (Q2 + Q4). (A–C) denote zein peptides, model, and control in the prevention group, respectively. (D–F) denote zein peptides, model, and control in the treatment group, respectively. (G,H) represent cell distribution percentage (%) of prevention group and treatment group, respectively. Different letters above the columns indicate that the means of different groups were significantly different (p < 0.05).
Figure 4
Figure 4
Volcano diagram of differentially expressed genes from zein peptides-treated group and control group. The genes with significantly up-regulated expression are in red, the genes with significantly down-regulated expression are in blue, and the genes with no significantly differential expression are in gray.
Figure 5
Figure 5
The proposed signaling pathway in zein peptides-treated C2C12 cells.
See this image and copyright information in PMC

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