Molecular Cellular Mechanisms of Peptide Regulation of Melatonin Synthesis in Pinealocyte Culture

It has been demonstrated that short peptides play an important role in the transmission of biological information, modulation of transcription, and restoring genetically conditioned alterations occurring with age. Peptidergic regulation of homeostasis occupies an important place in physiological processes, which lead to the aging of cells, tissues, and organs, consisting in the involution of major regulatory systems-the nervous, the endocrine, and the immune. The effect of AED (Ala-Glu-Asp), KED (Lys-Glu-Asp), KE (Lys-Glu), AEDG (Ala-Glu-Asp-Gly) peptides and their compound on neuronal differentiation of human periodontal ligament stem cells (hPDLSCs) was studied by immunofluorescence and western blot analysis. Growth-Associated Protein 43 (GAP43), which implements neurotransmission mechanisms and neuroplasticity, demonstrated an increased expression in hPDLSCs cultured with a compound of all studied peptides and with KED alone. The peptide compound and KED, increase the expression of Nestin (neurofilament protein), expressed in early neuronal precursors in hPDLSCs cultures. Thus, the compound of peptides AEDG, KE, AED, and KED could promote the neuronal differentiation of hPDLSCs and be a promising tool for the study of peptides as a modulator of neurogenesis in neurodegenerative diseases studied in animal models.

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“…Increased melatonin synthesis in pineal gland during aging. 33,34 3. Induced retinal cells differentiation, retinaprotector.…”

Section: Kementioning

confidence: 99%

Effect of short peptides on neuronal differentiation of stem cells

Caputi

Trubiani

Sinjari

et al. 2019

Int J Immunopathol Pharmacol

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“…The tetrapeptide epitalon in in vivo and in vitro studies has antioxidant activity, regulates the functions of the pineal gland and melatonin synthesis, stimulates neuronal differentiation , has immunostimulating properties, reduces the risk of the development of tumor diseases, regulates the functional activity of the neuroimmunoendocrine system, helps to increase the telomere length in normal fibroblasts and blood and to overcome the Hayflick limit [3,5,7,14,21]. The goal of the work was to study the effect of the peptides vilon (KE) and epitalon (AEDG) on the expression of the ribosome protein L7A and the area of mitochondrial staining with MitoTracker Red in cell cultures of the human thymus and pineal gland.…”

Section: Ribosome Functioning With Agingmentioning

confidence: 99%

Influence of AEDG and KE Peptides on Mitochondrial Staining and the Expression of Ribosomal Protein L7A with Aging of the Human Pineal Gland and Thymus Cell In Vitro

et al. 2021

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New molecular targets for the geroprotective activity of AEDG (epitalon) and KE (vilon) peptides were verified via confocal laser scanning microscopy. It was shown that the aging of pineal and thymic cells in vitro led to a decrease in the staining of MitoTracker Red mitochondria and that there is a compensatory increase in the synthesis of L7A ribosomal protein. AEDG peptide increased the area of MitoTracker Red mitochondrial staining by 1.5 times and decreased by 22% the expression of ribosomal protein L7A in cultures of human pineal-gland cells with aging. KE peptide increased the area of MitoTracker Red mitochondrial staining by 1.5 times and decreased by 15% the expression of ribosomal protein L7A in cultures of human thymic cells with aging. The area of MitoTracker Red mitochondrial staining decreased and the compensatory expression of L7A ribosomal protein increased with aging of the pineal gland and thymic cells. Presumably, AEDG and KE peptides have a tissue-specific effect that normalizes the functions of mitochondria and ribosomes of pinealocytes and thymocytes.

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“…It was shown that the KE peptide regulates the expression of the EPS15, MCM10 homologue, Culline 5, APG5L, FUSED, ZNF01, FLJ12848 fis, ITPK1, SLC7A6, FLJ22439 fis, KIAA69799, FIA, KIAA690099, FLA2 peptides, FLJ10914, Gdap1, MSTP028, MLLT3 and PEPP2, and the synthesis of cytoskeleton proteins, cell proliferation and metabolism, which explains its high biological activity [ 103 ]. The tetrapeptide AEDG (Epitalon) stimulates the activity of the neuroimmunoendocrine system, normalizing the functions of the thymus and cardiovascular system in pathology and ageing through regulation of melatonin synthesis [ 104 ]. Due to its ability to regulate melatonin synthesis, the AEDG peptide can be considered as one of the possible agents in complex COVID-19 therapy.…”

Section: Main Textmentioning

confidence: 99%

Peptides: Prospects for Use in the Treatment of COVID-19

et al. 2020

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There is a vast practice of using antimalarial drugs, RAS inhibitors, serine protease inhibitors, inhibitors of the RNA-dependent RNA polymerase of the virus and immunosuppressants for the treatment of the severe form of COVID-19, which often occurs in patients with chronic diseases and older persons. Currently, the clinical efficacy of these drugs for COVID-19 has not been proven yet. Side effects of antimalarial drugs can worsen the condition of patients and increase the likelihood of death. Peptides, given their physiological mechanism of action, have virtually no side effects. Many of them are geroprotectors and can be used in patients with chronic diseases. Peptides may be able to prevent the development of the pathological process during COVID-19 by inhibiting SARS-CoV-2 virus proteins, thereby having immuno- and bronchoprotective effects on lung cells, and normalizing the state of the hemostasis system. Immunomodulators (RKDVY, EW, KE, AEDG), possessing a physiological mechanism of action at low concentrations, appear to be the most promising group among the peptides. They normalize the cytokines’ synthesis and have an anti-inflammatory effect, thereby preventing the development of disseminated intravascular coagulation, acute respiratory distress syndrome and multiple organ failure.

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Molecular Cellular Mechanisms of Peptide Regulation of Melatonin Synthesis in Pinealocyte Culture

Cited by 16 publications

References 13 publications

Effect of short peptides on neuronal differentiation of stem cells

Effect of short peptides on neuronal differentiation of stem cells

Influence of AEDG and KE Peptides on Mitochondrial Staining and the Expression of Ribosomal Protein L7A with Aging of the Human Pineal Gland and Thymus Cell In Vitro

Peptides: Prospects for Use in the Treatment of COVID-19

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