A pilot study on nitration/dysfunction of NK1 segment of myogenic stem cell activator HGF

Alaa Elgaabari, Nana Imatomi, Hirochika Kido, Miyumi Seki, Sakiho Tanaka, Yuji Matsuyoshi, Takashi Nakashima, Shoko Sawano, Wataru Mizunoya, Takahiro Suzuki, Mako Nakamura, Judy E. Anderson, Ryuichi Tatsumi

Research output: Contribution to journalArticlepeer-review

Abstract

Protein tyrosine residue (Y) nitration, a post-translational chemical-modification mode, has been associated with changes in protein activity and function; hence the accumulation of specific nitrated proteins in tissues may be used to monitor the onset and progression of pathological disorders. To verify the possible impact of nitration on postnatal muscle growth and regeneration, a pilot study was designed to examine the nitration/dysfunction of hepatocyte growth factor (HGF), a key ligand that is released from the extracellular tethering and activates myogenic stem satellite cells to enter the cell cycle upon muscle stretch and injury. Exposure of recombinant HGF (a hetero-dimer of α- and β-chains) to peroxynitrite induces Y nitration in HGF α-chain under physiological conditions. Physiological significance of this finding was emphasized by Western blotting that showed the NK1 segment of HGF (including a K1 domain critical for signaling-receptor c-met binding) undergoes nitration with a primary target of Y198. Peroxynitrite treatment abolished HGF-agonistic activity of the NK1 segment, as revealed by in vitro c-met binding and bromodeoxyuridine-incorporation assays. Importantly, direct-immunofluorescence microscopy of rat lower hind-limb muscles from two aged-groups (2-month-old “young” and 12-month-old “retired/adult”) provided in vivo evidence for age-related nitration of extracellular HGF (Y198). Overall, findings provide the insight that HGF/NK1 nitration/dysfunction perturbs myogenic stem cell dynamics and homeostasis; hence NK1 nitration may stimulate progression of muscular disorders and diseases including sarcopenia.

Original languageEnglish
Article number101295
JournalBiochemistry and Biophysics Reports
Volume31
DOIs
Publication statusPublished - Sep 2022

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry

Fingerprint

Dive into the research topics of 'A pilot study on nitration/dysfunction of NK1 segment of myogenic stem cell activator HGF'. Together they form a unique fingerprint.

Cite this