Abstract
Short peptides, vesugen and D-7, stimulated the synthesis of the proliferation-associated protein Ki-67, the expression of which decreased during aging in tissue-specific cell cultures obtained from young and old animals and in dissociated vascular endothelial cell cultures. Molecular docking methods were used to reveal the possibility of binding the vesugen and D-7 peptides to the promoter regions of the MKI67 gene, which encodes the Ki-67 protein. Both peptides have contact through the CATC sequence with core promoter 5'-agcctcaaccatcaggaaaacaagagt-3', which is located in the MKI67 gene (ENSG00000148773) from -14 to +12 bp relative to the transcriptional initiation site. Thus, the vasoprotective effect of vesugen, which was previously revealed in elder people, can be manifested through epigenetic regulation of the Ki-67 gene expression.
Similar content being viewed by others
References
Bashkireva, A.S. and Artamonova, V.G., Peptidergic correction of neurotic sates of the lorry drivers, Usp. Gerontol., 2012, vol. 25, no. 4, pp. 718–728.
Kitachev, K.V., Sazonov, A.B., Kozlov, K.L., et al., Role of vasoactive peptide for treatment of chronic arterial insufficiency of low limb, Usp. Gerontol., 2013, vol. 26, no. 2, pp. 292–296.
Pal’tsev, M.A., Kvetnoi, I.M., Polyakova, V.O., et al., Signal molecules: place and role in individual diagnostics, treatment, and prophylactics of important social diseases, Mol. Med., 2012, no. 5, pp. 3–8.
Anisimov, V.N. and Khavinson, V.Kh., Peptide bioregulation of aging: results and prospects, Biogerontology, 2010, vol. 11, no. 2, pp. 139–149.
Fedoreyeva, L.I., Kireev, I.I., Khavinson, V.Kh., and Vanyushin, B.F., Penetration of short fluorescence labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA, Biochemistry, 2011, vol. 76, no. 11, pp. 1505–1516.
Grigor’ev, E.I., Khavinson, V.Kh., Malinin, V.V., et al., Role of aqueous medium in mechanisms underlying the influence of immunoactive peptides in ultralow doses, Bull. Exp. Biol. Med., 2003, vol. 136, no. 2, pp. 150–154.
Huang, H., Kozekov, I.D., Kozekova, A., et al., Minor groove orientation of the KWKK peptide tethered via the N-terminal amine to the acrolein-derived 1,N2gamma-hydroxypropanodeoxyguanosine lesion with a trimethylene linkage, Biochemistry, 2010, vol. 27, no. 49, pp. 6155–6164.
Khavinson, V.Kh. and Malinin, V.V., Gerontological Aspects of Genome Peptide Regulation, Basel, Switzerland: Karger AG, 2005.
Khavinson, V.Kh., Grigoriev, E.I., Malinin, V.V., and Ryzhak, G.A., US Patent 7851449, 2010.
Khavinson, V.Kh., Solov’ev, A.Yu., Tarnovskaya, S.I., and Lin’kova, N.S., Mechanism of biological activity of short peptides: cell penetration and epigenetic regulation of gene expression, Biol. Bull. Rev., 2013, vol. 3, no. 6, pp. 451–455.
Khavinson, V.Kh., Linkova, N.S., Pronyaeva, V.E., et al., A method of creating a cell monolayer based on organotypic culture for screening of physiologically active substances, Bull. Exp. Biol. Med., 2012, vol. 153, no. 5, pp. 795–799.
Khavinson, V.Kh., Nikolsky, I.S., Nikolskaya, V.V., et al., Effect of tripeptides on lymphoid and stem cells, Bull. Exp. Biol. Med., 2011, vol. 151, no. 6, pp. 722–725.
Khavinson, V.Kh., Polyakova, V.O., Linkova, N.S., et al., Peptides regulate cortical thymocytes differentiation, proliferation, and apoptosis, J. Amino Acids, 2011, vol. 2011, pp. 1–5.
Khavinson, V.Kh., Tarnovskaya, S.I., Linkova, N.S., et al., Short cell-penetrating peptides: a model of interactions with gene promoter site, Bull. Exp. Biol. Med., 2013, vol. 154, no. 3, pp. 403–408.
Lin’kova, N.S., Polyakova, V.O., Trofimov, A.V., et al., Peptidergic regulation of thymocyte differentiation, proliferation, and apoptosis during aging of the thymus, Bull. Exp. Biol. Med., 2011, vol. 151, no. 2, pp. 239–242.
Chemical Computing Group, Molecular Operating Environment, 2012.
Olivieri, F., Recchioni, R., Marcheselli, F., et al., Cellular senescence in cardiovascular diseases: potential age-related mechanisms and implications for treatment, Curr. Pharm. Des., 2013, vol. 19, no. 9, pp. 1710–1719.
Pei, D.-S., Qian, G.-W., Tian, H., et al., Analysis of human Ki-67 gene promoter and identification of the Sp1 binding sites for Ki-67 transcription, Tumour Biol., 2012, vol. 33, no. 1, pp. 257–266. doi: 10.1007/s13277011-0277-z
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © V.Kh. Khavinson, S.I. Tarnovskaya, N.S. Linkova, E.O. Gutop, E.V. Elashkina, 2014, published in Uspekhi Gerontologii, 2014, Vol. 27, No. 1, pp. 108–114.
Rights and permissions
About this article
Cite this article
Khavinson, V.K., Tarnovskaya, S.I., Linkova, N.S. et al. Epigenetic aspects of peptidergic regulation of vascular endothelial cell proliferation in aging. Adv Gerontol 5, 219–224 (2015). https://doi.org/10.1134/S2079057015040116
Published:
Issue Date:
DOI: https://doi.org/10.1134/S2079057015040116