Identification of novel peptide motifs in the serpin maspin that affect vascular smooth muscle cell function

S.e. Jenkinson, L.j. Brown, J. Ombor, J.a. Milburn, T. Smulders-srinivasan, S. Veuger, D.r. Edwards, R. Bass

    Research output: Contribution to journalArticle

    151 Downloads (Pure)

    Abstract

    Maspin is a non-inhibitory member of the serpin family that affects cell behaviours related to migration and survival. We have previously shown that peptides of the isolated G α-helix (G-helix) domain of maspin show bioactivity. Migration, invasion, adhesion and proliferation of vascular smooth muscle cells (VSMC) are important processes that contribute to the build-up of atherosclerotic plaques. Here we report the use of functional assays of these behaviours to investigate whether other maspin-derived peptides impact directly on VSMC; focusing on potential anti-atherogenic properties. We designed 18 new peptides from the structural moieties of maspin above ten amino acid residues in length and considered them beside the existing G-helix peptides. Of the novel peptides screened those with the sequences of maspin strand 4 and 5 of beta sheet B (S4B and S5B) reduced VSMC migration, invasion and proliferation, as well as increasing cell adhesion. A longer peptide combining these consecutive sequences showed a potentiation of responses, and a 7-mer contained all essential elements for functionality. This is the first time that these parts of maspin have been highlighted as having key roles affecting cell function. We present evidence for a mechanism whereby S4B and S5B act through ERK1/2 and AMP-activated protein kinase (AMPK) to influence VSMC responses.
    Original languageEnglish
    Pages (from-to)336-344
    JournalBiochimica et Biophysica Acta - Molecular Cell Research
    Volume1864
    Issue number2
    Early online date23 Nov 2016
    DOIs
    Publication statusPublished - 28 Feb 2017

    Fingerprint Dive into the research topics of 'Identification of novel peptide motifs in the serpin maspin that affect vascular smooth muscle cell function'. Together they form a unique fingerprint.

  • Cite this