Studying Antifatigue Mechanism of Tyr-Pro-Leu-Pro in Exercise Mice Using Label-Free Proteomics

J Agric Food Chem. 2024 Jan 31;72(4):2178-2192. doi: 10.1021/acs.jafc.3c07642. Epub 2024 Jan 23.

Abstract

In our previous study, yeast-derived peptide Tyr-Pro-Leu-Pro (YPLP) was found to prolong treadmill time and relieve muscle fatigue in ICR mice. The present study aimed to further investigate the antifatigue mechanism of YPLP. Three doses of YPLP (10, 25, and 50 mg/kg·d) were given to exercise mice for 4 weeks. Results showed that YPLP reduced the oxidative response via the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway and promoted energy metabolism through the AMP-activated protein kinase (AMPK) pathway. Label-free proteomics results showed that 81 differential abundance proteins (DAPs) were regulated by high-dose YPLP. These DAPs belonged to proteasome, mitochondrial, and muscle proteins. YPLP was mainly involved in proteasome, aminoacyl-tRNA biosynthesis, focal adhesion, and MAPK signal pathways to enhance muscle endurance. Furthermore, real-time quantitative PCR and Western blotting results proved that YPLP upregulated Psmd14 expression and downregulated p38 MAPK expression. Overall, this study revealed the mechanism behind YPLP to alleviate exercise fatigue.

Keywords: antioxidant; metabolic pathway; muscle fatigue; proteomics; yeast-derived peptide.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Dipeptides*
  • Mice
  • Mice, Inbred ICR
  • Proteasome Endopeptidase Complex* / genetics
  • Proteomics*

Substances

  • tyrosyl-proline
  • leucylproline
  • Proteasome Endopeptidase Complex
  • AMP-Activated Protein Kinases
  • Dipeptides