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

Abstract

Identification of novel peptide motifs in the serpin maspin that affect vascular smooth muscle cell function, BBAMolecular Cell Research (2016Research ( ), doi:10.1016Research ( /j.bbamcr.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 2 AbstractMaspin 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. Graphic AbstractSchematic depiction of the effect of maspin peptides on VSMC behaviours

Angiotensin II, Hypercholesterolemia, and Vascular Smooth Muscle Cells: A Perfect Trio for Vascular Pathology

“…Gene Ontology (GO) analysis identified that the major discriminators between atherosclerotic and non-atherosclerotic patients were those involved with superoxide radical generation, and particularly superoxide dismutase (SOD1) overexpression. An additional protein uncovered in this study was the SERPIN family-related protein SERPINE2, which is note-worthy in that members of the SERPIN family have recently been identified as key regulators of VSMC migration, adhesion, signal transduction and proliferation, linking atherogenic stimuli and VSMC dysfunction [ 30 , 31 ]. Ang II exerts cellular damage via the production of reactive oxygen species in VSMC and its paracrine effects on other cells in proximity in an NAD(P)H-dependent mechanism [ 32 ].…”