Cell‐physiological effects of elastin derived (VGVAPG)_n oligomers in a unicellular model system

Abstract

Elastin is one of the most significant components of the extracellular matrix, which supports the stretchiness of the blood vessels via its helical structure and cross-links. Enzymatic decomposition of this protein could induce chemotactic responses of cell populations in the surrounding tissues by several peptide sequences, e.g. XGXXPG. In our present work the VGVAPG variant and its oligomers were studied. The objective of the experiments was to learn (i) whether the chemotactic effect of these peptides is general in different levels of phylogeny: (ii) whether increasing the number of monomer units influences the chemotactic behaviour of the cell? The trimer had the strongest chemoattractant effect in a wide concentration range (10(-12) - 10(-7) M), while the monomer and the pentamer were chemorepellent. All tri-, tetra-, penta- and hexamers could chemotactically select subpopulations with a high chemotactic responsiveness to the identical peptide, in the long term. With regard to its repellent effect, the pentamer had a negative effect on phagocytosis. All six oligomers had a growth-promoter effect in Tetrahymena. The characteristic cell-physiological effects of VGVAPG oligomers signal that molecules of the extracellular matrix can induce identical responses even in lower levels of phylogeny, e.g. in the Ciliates.

Locally generated VGVAPG and VAPG elastin‐derived peptides amplify melanoma invasion via the galectin‐3 receptor

“…To find an explanation for the diverse activities of the 2 elastin-derived peptides, the Circular Dichroism (CD) spectra of VAPG were measured in water and trifluoroethanol respectively (data not shown). However comparing the spectra of VAPG with the previously measured spectra of VGVAPG, 59 no significant difference could be seen. In both cases the CD spectra in water reflect the presence of different conformations, a mixture of unordered extended conformers.…”

“…59 H-VPVGGA-OH and H-PGVA-OH were synthesized also stepwise on Wang resin (capacity, 0.9 mmol/g), with Fmoc technique using N,N-diisopropylcarbodiimide/1-hydroxybenzotriazole as coupling agent. The peptides were cleaved from the resin with a mixture of trifluoroacetic acid, triisiopropyl silane, water (95:2.5:2.5); then resin was filtered off and the solvent was evaporated in vacuo.…”