title: Identification of novel peptide motifs in the serpin maspin that affect vascular smooth muscle cell function.
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.
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK; Institute of Cardiovascular Sciences, Institute for Biomedical Research, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: Jenkinson
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Brown
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.
authors.forename: J
authors.initials: J
authors.lastname: Ombor
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Milburn
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.
authors.forename: T
authors.initials: T
authors.lastname: Smulders-Srinivasan
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.
authors.forename: S
authors.initials: S
authors.lastname: Veuger
authors.affiliation: Faculty of Medicine and Health Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Edwards
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK. Electronic address: r.bass@uea.ac.uk.
authors.forename: R
authors.initials: R
authors.lastname: Bass
mesh_terms: D000595:Amino Acid Sequence; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D020935:MAP Kinase Signaling System; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology*; D015843:Serpins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D019012:Integrin beta1; D010446:Peptide Fragments; C085344:SERPIN-B5; D015843:Serpins
keywords: Adhesion; Invasion; Maspin; Migration; Proliferation; Serpin peptide