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Khavinson V.Kh.,RAS Pavlov Institute of Physiology | Tendler S.M.,Karolinska University Hospital | Tendler S.M.,Saint Petersburg Institute of Bioregulation and Gerontology | Vanyushin B.F.,Moscow State University | And 7 more authors.
Lung | Year: 2014

Introduction: Some studies have shown that peptides have high treatment potential due to their biological activity, harmlessness, and tissue-specific action. Tetrapeptide Ala-Asp-Glu-Leu (ADEL) was effective on models of acute bacterial lung inflammation, fibrosis, and toxic lung damage in several studies. Methods: We measured Ki67, Mcl-1, p53, CD79, and NOS-3 protein levels in the 1st, 7th, and 14th passages of bronchoepithelial human embryonic cell cultures. Gene expression of NKX2-1, SCGB1A1, SCGB3A2, FOXA1, FOXA2, MUC4, MUC5AC, and SFTPA1 was measured by real-time polymerase chain reaction. Using the methods of spectrophotometry, viscometry, and circular dichroism, we studied the ADEL-DNA interaction in vitro. Results: Peptide ADEL regulates the levels of Ki67, Mcl-1, p53, CD79, and NOS-3 proteins in cell cultures of human bronchial epithelium in various passages. The strongest activating effect of peptide ADEL on bronchial epithelial cell proliferation through Ki67 and Mcl-1 was observed in "old" cell cultures. ADEL regulates the expression of genes involved in bronchial epithelium differentiation: NKX2-1, SCGB1A1, SCGB3A2, FOXA1, and FOXA2. ADEL also activates several genes, which reduced expression correlated with pathological lung development: MUC4, MUC5AC, and SFTPA1. Spectrophotometry, viscometry, and circular dichroism showed ADEL-DNA interaction, with a binding region in the major groove (N7 guanine). Conclusions: ADEL can bind to specific DNA regions and regulate gene expression and synthesis of proteins involved in the differentiation and maintenance of functional activity of the bronchial epithelium. Through activation of some specific gene expression, peptide ADEL may protect the bronchial epithelium from pulmonary pathology. ADEL also may have a geroprotective effect on bronchial tissue. © 2014 Springer Science+Business Media New York.


Khavinson V.Kh.,RAS Pavlov Institute of Physiology | Linkova N.S.,Saint Petersburg Institute of Bioregulation and Gerontology | Kvetnoy I.M.,Saint Petersburg Institute of Bioregulation and Gerontology | Kvetnaia T.V.,Saint Petersburg Institute of Bioregulation and Gerontology | Polyakova V.O.,Saint Petersburg Institute of Bioregulation and Gerontology
Bulletin of Experimental Biology and Medicine | Year: 2012

The effects of epithalone and vilone peptides on the synthesis of melatonin and factors involved in this process, arylalkylamine-N-acetyltransferase (AANAT) enzyme and pCREB transcription protein, were studied in rat pinealocyte culture. Epithalone stimulated AANAT and pCREB synthesis and increased melatonin level in culture medium. Simultaneous addition of norepinephrine and peptides into the culture potentiated the expression of AANAT and pCREB. © 2012 Springer Science+Business Media, Inc.


Khavinson V.Kh.,RAS Pavlov Institute of Physiology | Lin'kova N.S.,Saint Petersburg Institute of Bioregulation and Gerontology | Polyakova V.O.,Russian Academy of Medical Sciences | Durnova A.O.,Russian Academy of Medical Sciences | And 2 more authors.
Bulletin of Experimental Biology and Medicine | Year: 2014

We studied the effect of polypeptide complex isolated from calf kidney and short peptides T-31 (AED) and T-35 (EDL) on the expression of signaling molecules, markers of cell renewal (Ki-67, p53), remodeling of the extracellular matrix (MMP-14), and immune response (IL-8) in primary kidney cell cultures during aging. The complex of renal polypeptides and T-31 peptide activate cell renewal processes during aging of the renal epithelium, while gelatinase MMP-14 is the target of T-35 peptide. © 2014 Springer Science+Business Media.


Khavinson V.,Saint Petersburg Institute of Bioregulation and Gerontology | Ribakova Y.,Russian Academy of Medical Sciences | Kulebiakin K.,Moscow State University | Vladychenskaya E.,Moscow State University | And 3 more authors.
Rejuvenation Research | Year: 2011

The synthetic tripeptide pinealon (Glu-Asp-Arg) demonstrates dose-dependent restriction of reactive oxygen species (ROS) accumulation in cerebellar granule cells, neutrophils, and pheochromocytoma (PC12) cells, induced by oxidative stress stimulated by receptor-dependent or-independent processes. At the same time, pinealon decreases necrotic cell death measured by the propidium iodide test. The protective effect of pinealon is accompanied with a delayed time course of ERK 1/2 activation and modification of the cell cycle. Because restriction of ROS accumulation and cell mortality is saturated at lower concentrations, whereas cell cycle modulation continues at higher concentrations of pinealon, one can conclude that besides its known antioxidant activity, pinealon is able to interact directly with the cell genome. © 2011 Mary Ann Liebert, Inc.


Mendzheritskii A.M.,Pedagogical Institute of the South Federal University | Karantysh G.V.,Pedagogical Institute of the South Federal University | Abramchuk V.A.,Pedagogical Institute of the South Federal University | Ryzhak G.A.,Saint Petersburg Institute of Bioregulation and Gerontology
Advances in Gerontology | Year: 2014

The effects of peptide geroprotectors, such as cortexin and pinealon, on the training of rats of different ages and the caspase-3 system in their brain structures were studied in the experimental model of acute hypoxic hypoxy. Regional changes were identified in the activity and the content of caspase-3 in the cerebral cortex and brainstem structures of young and old rats under the influence of peptide preparations. It is suggested that the functional state of the caspase-3 system in the brain is one of the reasons for the ability of animals to learn. Compared with cortexin, pinealon has a greater positive effect on the learning of both young and old animals in the Morris labyrinth. © 2014 Pleiades Publishing, Ltd.


Khavinson V.K.,Saint Petersburg Institute of Bioregulation and Gerontology
Uspekhi fiziologicheskikh nauk | Year: 2013

The review considers literature data and own results of research of cytokines functions and their effects on hemostatic system and life span. The data of age-related changes in the hemostatic system is presented in this article. A big part of the review is devoted to the action of regulatory peptides (RP) on various body systems. It is established that the RP can normalize the expression of cytokine genes in humans and animals with stress and pathological conditions. Effect of RP on the cytokines has geroprotective action, which is based on anti-oxidant, anti-inflammatory action, stimulation of cell proliferation and differentiation, as well as a normalizing effect on the immune system and hemostasis.


Sidorenko A.V.,European Center for Social Welfare Policy and Research | Mikhailova O.N.,Saint Petersburg Institute of Bioregulation and Gerontology
Advances in Gerontology | Year: 2014

In this article, government policies on ageing in the CIS countries and Georgia (CIS+) are discussed. The implementation process of the Madrid International Plan of Action on Aging (MIPAA) from 2002 to 2012 was chosen as a framework for analyzing the government policy on ageing. The article begins with a concise overview of the demographic situation in the CIS+ countries, which belong to various stages of demographic transition. In conclusion, policy goals for implementing MIPAA during its third implementation cycle (2013-2017) are presented. © 2014 Pleiades Publishing, Ltd.


PubMed | Saint Petersburg Institute of Bioregulation and Gerontology
Type: | Journal: Journal of amino acids | Year: 2012

The processes of differentiation, proliferation, and apoptosis were studied in a cell culture of human cortical thymocytes under the influence of short peptides T-32 (Glu-Asp-Ala) and T-38 (Lys-Glu-Asp). Peptides T-32 and T-38 amplified cortical thymocytes differentiation towards regulatory T cells, increased their proliferative activity, and decreased the level of apoptosis. Moreover, peptides under study stimulated proliferative and antiapoptotic activity of the mature regulatory T cells.


PubMed | Saint Petersburg Institute of Bioregulation and Gerontology
Type: Journal Article | Journal: Rejuvenation research | Year: 2011

The synthetic tripeptide pinealon (Glu-Asp-Arg) demonstrates dose-dependent restriction of reactive oxygen species (ROS) accumulation in cerebellar granule cells, neutrophils, and pheochromocytoma (PC12) cells, induced by oxidative stress stimulated by receptor-dependent or -independent processes. At the same time, pinealon decreases necrotic cell death measured by the propidium iodide test. The protective effect of pinealon is accompanied with a delayed time course of ERK 1/2 activation and modification of the cell cycle. Because restriction of ROS accumulation and cell mortality is saturated at lower concentrations, whereas cell cycle modulation continues at higher concentrations of pinealon, one can conclude that besides its known antioxidant activity, pinealon is able to interact directly with the cell genome.


PubMed | Saint Petersburg Institute of Bioregulation and Gerontology
Type: | Journal: Current aging science | Year: 2016

We have provided an overview, based on the literature and our data. In accordance with the theory of D. Harman free radical processes cause damages that can accumulate and contribute to aging of the organism. Atherosclerosis and diabetes are developing for a long time so they are manifested predominantly in old age. We found an increase in the level of free radical peroxidation products and decrease in the activity of antioxidant enzymes in the tissues of animals with experimental atherosclerosis. Similar changes were found by in the blood of patients with atherosclerosis and aortic autopsy material with atherosclerotic lesions. Thus, it was revealed that oxidative stress occured under atherosclerosis, and we attributed the arteriosclerosis to free radical pathologies. Later it was discovered by different authors that oxidized low density lipoproteins (LDL) and malonyldialdehyde-modified LDL accumulated during atherogenesis, causing damages of vascular wall. Under diabetic hyperglycemia glucose co-oxidized during free radical lipoperoxidation. This process promoted the transformation of oxidative stress to carbonyl stress with accumulation of biologically active dicarbonyls, including glyoxal and methylglyoxal. We show that the glyoxal-modified LDL were captured by cultured macrophages with a higher efficiency than the MDA-modified LDL. This could facilitate the more rapid development of lipoidosis in the vessel wall (due to the formation of foam cells) and manifestation of atherosclerosis under diabetes. We found that in patients with diabetes there was a sharp decrease in the activity of antioxidant enzymes as a result of the modification of the active center under development of carbonyl stress. We expressed a hypothesis about a common molecular mechanism of vascular wall damages under atherosclerosis and diabetes.

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