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Monomeric C-mannosyl tryptophan is a degradation product of autophagy in cultured cells.

Authors
  • Minakata, Shiho1
  • Inai, Yoko1
  • Manabe, Shino2, 3
  • Nishitsuji, Kazuchika1
  • Ito, Yukishige4
  • Ihara, Yoshito5
  • 1 Department of Biochemistry, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, 641-0012, Japan. , (Japan)
  • 2 Laboratory of Functional Molecule Chemistry, Pharmaceutical Department and Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo, 142-8501, Japan. , (Japan)
  • 3 Research Center for Pharmaceutical Development, Graduate School of Pharmaceutical Sciences & Faculty of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan. , (Japan)
  • 4 RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. , (Japan)
  • 5 Department of Biochemistry, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, 641-0012, Japan. [email protected] , (Japan)
Type
Published Article
Journal
Glycoconjugate Journal
Publisher
Springer-Verlag
Publication Date
Oct 01, 2020
Volume
37
Issue
5
Pages
635–645
Identifiers
DOI: 10.1007/s10719-020-09938-8
PMID: 32803368
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

C-Mannosyl tryptophan (C-Man-Trp) is a unique glycosylated amino acid present in various eukaryotes. The C-Man-Trp structure can be found as a monomeric form or a part of post-translational modifications within polypeptide chains in living organisms. However, the mechanism of how monomeric C-Man-Trp is produced has not been fully investigated. In this study, we assessed levels of cellular C-Man-Trp by ultra performance liquid chromatography with a mass spectrometry assay system, and investigated whether the cellular C-Man-Trp is affected by autophagy induction. The intracellular C-Man-Trp level was significantly increased under serum and/or amino acid starvation in A549, HaCaT, HepG2, NIH3T3, and NRK49F cells. The increase in C-Man-Trp was also observed in NIH3T3 cells treated with rapamycin, an autophagy inducer. The up-regulation of C-Man-Trp caused by starvation was reversed by the inhibition of lysosomal enzymes. We further showed that C-Man-Trp is produced by incubating a synthetic C-mannosylated peptide (C-Man-Trp-Ser-Pro-Trp) or thrombospondin (TSP) in a lysosomal fraction that was prepared from a mouse liver, which provides supporting evidence that C-Man-Trp is a degradation product of the C-mannosylated peptide or protein following lysosome-related proteolysis. Taken together, we propose that the autophagic pathway is a novel pathway that at least partly contributes to intracellular C-Man-Trp production under certain conditions, such as nutrient starvation.

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