Treatment with L-type amino acid transporter 1 inhibitor JPH203 enhances protein synthesis in C2C12 myotubes

Excessive muscle protein synthesis causes skeletal muscle hypertrophy. Essential amino acids are substrates for muscle proteins and stimulate muscle protein synthesis. Several essential amino acids are taken up into muscle cells through L-type amino acid transporter 1 (LAT1). However, LAT1 may influence protein synthesis in an amino acid uptake-independent manner. Here, we investigated the effects of LAT1 inhibition on protein synthesis in C2C12 myotubes and the associated mechanisms. JPH203 (50 μM), a selective inhibitor of LAT1, stimulated protein synthesis without changing expression of phosphorylated p70S6K (T389) and 4EBP1 (T37/46), an indicator of mTORC1 activity. Culturing in amino acid-free media did not suppress JPH203-induced protein synthesis. The mTORC1 inhibitor rapamycin (100 nM) did not suppress JPH203-induced protein synthesis. ATP-competitive mTOR inhibitor AZD8055 (1 μM) suppressed JPH203-induced protein synthesis. JPH203 treatment increased intracellular glutamine concentration. These results suggest that inhibition of LAT1 function augments muscle protein synthesis, possibly through the activation of rapamycin-insensitive mTOR signaling; elevated intracellular glutamine levels may contribute to the enhancement of muscle protein synthesis induced by LAT1 inhibition.

• Publication year

  2025

• Venue

  Scientific Reports

• Publication date

  2025-11-19

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/s41598-025-24534-2PMID 41257941PMCID 12630651
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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