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Epigenetic Regulation of “Aged” Heterochromatin by Peptide Bioregulator Cortagen

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Abstract

Peptide bioregulator Cortagen (Ala-Glu-Asp-Pro) in humans demonstrated a pronounced therapeutic effect up on the structural and functional recovery of the damaged peripheral nerve tissue. The synthetic peptide Cortagen was obtained by directed synthesis based on amino acid analysis of natural brain cortex peptide preparation Cortexin. The effect of synthetic peptide bioregulator Cortagen on total, constitutive [pericentromeric, nucleolus organizer regions (NOR)] heterochromatin and facultative (transcriptionally inactive euchromatin) heterochromatin has been studied. We used a molecular-cytogenetic methods: differential scanning calorimetry; activity of ribosomal genes of acrocentric chromosome satellite stalks—NORs; polymorphism of structural pericentromeric C-heterochromatin; variability of the facultative heterochromatin (FH) in cultivated lymphocytes from individuals at the age of 80 and older. We show that peptide bioregulator Cortagen induces unrolling deheterochromatinization (decondensation) of total heterochromatin; activates synthetic processes of ribosomal genes as a result of deheterochromatinization of satellite stalks of acrocentric chromosomes; does not induce deheterochromatinization of pericentromeric structural heterochromatin; and releases repressed genes because of the condensation of euchromatic regions forming FH. Our data are important because it provides new information on the remodeling effects of FH induced by peptide bioregulator Cortagen in aging and aging pathologies, and may lead to the development of a therapeutic treatment.

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References

  • Andriani W, Granstrem O, Romano E et al (2009) Modulatory effects of cortexin and Cortagen on locomotoractivity and anxiety-related behavior in mice. Open Neuropsychopharmacol 2:22–29

    Article  Google Scholar 

  • Anisimov S, Khavinson V, Anisimov V (2004) Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray. Neuroendocrinol Lett 25:87–93

    CAS  PubMed  Google Scholar 

  • Anisimov V, Khavinson V, Mikhailova O (2011) Biogerontology in Russia: from past to future. Biogerontology 12:47–60

    Article  PubMed  Google Scholar 

  • Canzio D, Liao M, Naber N et al (2013) A conformational switch in HP1releases auto-inhibition to drive heterochromatin assembly. Nature 496:377–381

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cardellini E, Cinelli S, Gianfranceschi G et al (2000) Differential scanning calorimetry of chromatin at different level of condensation. Mol Biol Rep 27:175–180

    Article  CAS  PubMed  Google Scholar 

  • Cavazza C, Brizzolara G, Lazarinni G et al (1991) Thermodinamics of condensation of nuclear chromatin. A differential scanning calorimetry of the salt-dependent structural transitions. Biochemistry 30:9060–9072

    Article  CAS  PubMed  Google Scholar 

  • Dialynas G, Vitalini M, Wallrath L (2008) Linking heterochromatin protein 1 (HP1) to cancer progression. Mutat Res 647:13–28

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Elcock L, Bridge J (2010) Exploring the relationship between interphase gene positioning, transcriptional regulation and the nuclear matrix. Biochem Soc Trans 38:263–267

    Article  CAS  PubMed  Google Scholar 

  • Escamilla-Del-Arenal M, Teixeira da Rocha S, Heard E (2011) Evolutionary diversity and developmental regulation of X-chromosome inactivation. Hum Genet 130(2):307–327

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fernandez R, Barragan M, Marchal J et al (2002) New C-band protocol by heat denaturation in the presence of formamide. Hereditas 137:145–148

    Article  CAS  PubMed  Google Scholar 

  • Gao H, Zhang Q, Yu Z, He Q (2014) Cell-penetrating Peptide based intelligent liposomal systems for enhanced drug delivery. Curr Pharm Biotechnol 15:210–219

    Article  CAS  PubMed  Google Scholar 

  • Gilson E, Magdinier F (2009) Chromosomal position effect and aging. In: Tollefsbol TO (ed) Epigenetics and aging. Springer, New York, pp 151–175

    Google Scholar 

  • Hawley R, Arbel T (1993) Yeast genetics and the fall of classical view of meiosis. Cell 72:301–303

    Article  CAS  PubMed  Google Scholar 

  • Herranz M, Esteller M (2007) DNA methylation and histone modifications in patients with cancer. Method Mol Biol 361:25–62

    CAS  Google Scholar 

  • Jokhadze T, Buadze T, Gaiozishvili M et al (2012) Deheterochromatinization of the chromatin in old age induced by oligopeptide bioregulator (Lyz-Glu-Asp-Pro). Georgian Med News 11:76–82

    Google Scholar 

  • Khavinson V, Lezhava T, Monaselidze J et al (2002) Effect of Livagen peptide of chromosome activation in lymphocyte from old people. Bull Exp Biol Med 134:389–392

    Article  CAS  PubMed  Google Scholar 

  • Khavinson V, Lezhava T, Monaselidze J et al (2003) Peptide Epitalon activates chromatin at the old age. Neuroendocrinol Lett 24:329–333

    CAS  PubMed  Google Scholar 

  • Khavinson V, Lin’kova N, Tarnovskaya S et al (2014) Short peptides stimulate serotonin expression in cells of brain cortex. Bull Exp Biol Med 157(1):77–80

    Article  CAS  PubMed  Google Scholar 

  • Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705

    Article  CAS  PubMed  Google Scholar 

  • Lehner B, Sandner B, Marschallinger J et al (2011) The dark side of BrdU in neural stem cell biology: detrimental effects on cell cycle, differentiation and survival. Cell Tissue Res 345(3):313–328

    Article  CAS  PubMed  Google Scholar 

  • Lezhava T (1984) Heterochromatinization as a key factor of aging. Mech Ageing Dev 28:279–288

    Article  CAS  PubMed  Google Scholar 

  • Lezhava T (2001) Chromosome and aging: genetic conception of aging. Biogerontology 2:253–260

    Article  CAS  PubMed  Google Scholar 

  • Lezhava T (2006) Human chromosomes and aging from 80 to 114 years. Nova Biomedical, New York, USA

    Google Scholar 

  • Lezhava T, Bablishvili N (2003) Reactivation of heterochromatin induced by sodium hydrophosphate at the old age. Proc Georg Acad Sci Biol Ser B 1:1–5

    Google Scholar 

  • Lezhava T, Khavinson V, Monaselidze J et al (2004) Vilon-induced reactivation of chromatin in cultured lymphocytes from old people. Biogerontology 4:73–79

    Article  Google Scholar 

  • Lezhava T, Monaselidze J, Jokhadze T et al (2011) Gerontology research in Georgia. Biogerontology 12:87–91

    Article  PubMed Central  PubMed  Google Scholar 

  • Li E, Zhang Y (2014) DNA methylation in mammals. Cold Spring Harb Perspect Biol. doi:10.1101/cshperspect.a019133

    PubMed  Google Scholar 

  • Lobov I, Podgornaya O (1999) The role of the nuclear matrix proteins in heterochromatin assembly. Cytologia 41:562–573

    CAS  Google Scholar 

  • Lundgren M, Chow C, Sabbattini P et al (2000) Transcription factor dosage affects changes in higher order chromatin structure associated with activation of heterochromatin gene. Cell 103:733–743

    Article  CAS  PubMed  Google Scholar 

  • Mazin A (2009) Suicidal function of DNA methylation in age-related genome disintegration. Ageing Res Rev 8:314–327

    Article  CAS  PubMed  Google Scholar 

  • Monaselidze J, Abuladze M, Asatiani N et al (2006) Characterization of chromium-induced apoptosis in cultured mammalian cells. A different scanning calorimetry study. Thermochemia Acta 441:8–15

    Article  CAS  Google Scholar 

  • Monaselidze J, Bregadze V, Barbakadze Sh, et al (2008) Influence of metal ions of thermodina stability of leukemic DNA in vivo. Microcalorimetry investigation, Proceeding of the 10th International Symposium of Metal Ions in Biology and Medicine, Bastia France May 19–22 ed. Philippe Collery 10:451–457

  • Patil S, Lubs H (1971) Classification of 9 h regions of human acrocentric chromosomes. Humangenetik 13:157–159

    Article  CAS  PubMed  Google Scholar 

  • Prokofieva-Belgovskaya A (1986) Chromatin regions of chromosomes. Nauka, Moskow

    Google Scholar 

  • Stitou S, de la Diaz Guardia R, Jimenes R, Bugrous M (2000) Inactive ribosomal cistrons are spread throughout the B chromosomes of Rattus (Rodential Muridal) implactions for their origin and evolution. Chromosome Res 8:305–311

    Article  CAS  PubMed  Google Scholar 

  • Trere D (2000) Ag-NOR staining and quantification. Micron 31:127–131

    Article  CAS  PubMed  Google Scholar 

  • Trojer P, Reinberg D (2007) Facultative Heterochromatin. Is there a distinctive molecular signature? Mol Cell 28:1–13

    Article  CAS  PubMed  Google Scholar 

  • Vaquero A (2009) The conserved role of sirtuins in chromatin regulation. Int J De Biol 53:303–322

    CAS  Google Scholar 

  • Yu Z, Li J, Zhu J et al (2014) A synthetic transmembrane segment derived from TRPV4 channel self-assembles into potassium-like channels to regulate vascular smooth muscle cell membrane potential. J Mat Chem B 2:3809–3818

    Article  CAS  Google Scholar 

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Acknowledgments

This article is dedicated to the memory of Professor A.A. Prokofieva-Belgovskaya from her grateful students.

Conflict of interest

Teimuraz Lezhava, Jamlet Monaselidze, Tinatin Jokhadze and Maia Gaiozishvili confirm that this article content has no conflicts of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Human and Animal Rights

Samples of peripheral venous blood were obtained from individuals of 80 years and older, and from 20 to 40 years old individuals. Biological material (peripheral blood) was collected out in accordance with international requirements, Research object-isolated lymphocytes for cultivation (in vitro). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain studies with animal subjects.

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Lezhava, T., Monaselidze, J., Jokhadze, T. et al. Epigenetic Regulation of “Aged” Heterochromatin by Peptide Bioregulator Cortagen. Int J Pept Res Ther 21, 157–163 (2015). https://doi.org/10.1007/s10989-014-9443-7

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  • DOI: https://doi.org/10.1007/s10989-014-9443-7

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