Inhibition of glutaminyl cyclase attenuates cell migration modulated by monocyte chemoattractant proteins

Yi Ling Chen, Kai Fa Huang, Wen Chih Kuo, Yan Chung Lo, Yu May Lee, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

QC (glutaminyl cyclase) catalyses the formation of N-terminal pGlu (pyroglutamate) in peptides and proteins. pGlu formation in chemoattractants may participate in the regulation of macrophage activation and migration. However, a clear molecular mechanism for the regulation is lacking. The present study examines the role of QC-mediated pGlu formation on MCPs (monocyte chemoattractant proteins) in inflammation. We demonstrated in vitro the pGlu formation on MCPs by QC using MS. A potent QC inhibitor, PBD150, significantly reduced the N-terminal uncyclized-MCP-stimulated monocyte migration, whereas pGlu-containing MCP-induced cellmigrationwas unaffected.QC small interfering RNA revealed a similar inhibitory effect. Lastly, we demonstrated that inhibiting QC can attenuate cell migration by lipopolysaccharide. These results strongly suggest that QC-catalysed N-terminal pGlu formation of MCPs is required for monocyte migration and provide new insights into the role of QC in the inflammation process. Our results also suggest that QC could be a drug target for some inflammatory disorders.

Original languageEnglish
Pages (from-to)403-412
Number of pages10
JournalBiochemical Journal
Volume442
Issue number2
DOIs
Publication statusPublished - Mar 1 2012
Externally publishedYes

Keywords

  • Chemokine
  • Glutaminyl cyclase (QC)
  • Lipopolysaccharide (LPS)
  • Monocyte
  • Monocyte chemoattractant protein (MCP)
  • Pyroglutamate (pGlu)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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