N. S. Lin’kova

Mechanism of biological activity of short peptides: Cell penetration and epigenetic regulation of gene expression

Data on various aspects of the molecular and cellular mechanism of the biological activity of short peptides used as potential drugs were analyzed. Based on the published data and our own results, a possible mechanism of the penetration of short peptides into the cytoplasm and cell nucleus is considered. In addition, the possibility of the involvement of short peptides in the mechanisms of the epigenetic regulation of gene expression via their complimentary interaction with promoter regions of genes in DNA is substantiated.

Peptides Regulate Expression of Signaling Molecules in Kidney Cell Cultures during In Vitro Aging

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.

Short Peptides Stimulate Serotonin Expression in Cells of Brain Cortex

Peptides Glu-Asp-Arg and Lys-Glu-Asp stimulate serotonin expression in aging cultures of brain cortex cells. Peptide regulation of 5-tryptophan hydroxylase gene encoding the enzyme involved in serotonin synthesis was demonstrated by the molecular docking method. The CCTGCC nucleotide sequence in 5-tryptophan hydroxylase gene was found to be complementary to these peptides. Hence, Glu-Asp-Arg and Lys-Glu-Asp peptides epigenetically regulate serotonin synthesis in the brain cortex, which indicates their neuro- and geroprotective activities.

Molecular Aspects of Anti-Atherosclerotic Effects of Short Peptides

We studied molecular mechanisms of the vasoprotective effects of tripeptide T-38 and dipeptide RR-1. Short peptides T-38 and the RR-1 activate the processes of cell renewal in organotypic and dissociated cultures of vascular cells during aging by increasing the expression of Ki-67 and reducing the synthesis of p53 protein. T-38 and RR-1 reduce the synthesis of E-selectin, adhesion molecule involved in the formation of atherosclerotic plaques.

Effect of Low-Intensity Laser Radiation of the Red Spectrum on Some Properties of Erythrocytes in Wistar Rats

Laser radiation of different power had various effects on the properties of erythrocytes. An increase in the radiation power from 2.2 to 25 mW/cm2 was accompanied by a decrease in the erythrocyte sedimentation rate and an increase in erythrocyte filtration index. Radiation of 50 mW/cm2 induced abnormal erythrocyte aggregation. Increasing the time of irradiation at power intensity of 2.2 mW/cm2 did not potentiate its effect on the blood.

Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro

The effect peptides KE, KED, AED and AEDG on proliferation (Ki-67), regeneration and aging (CD98hc), apoptosis (caspase-3), and extracellular matrix remodeling (MMP-9) in skin fibroblasts during their aging in culture were studied by immunofluorescent confocal microscopy. All studied peptides inhibited MMP-9 synthesis that increases during aging of skin fibroblasts and enhanced the expression of Ki-67 and CD98hc that are less intensively synthesized during cell aging. Peptides AED and AEDG suppressed caspase-dependent apoptosis that increases during aging of cell cultures.

Effect of Polypeptides on Cell Proliferation and Apoptosis during Aging

Polypeptide complexes derived from the bronchi, blood vessels, muscles, kidneys, ovaries, testes, and retina stimulated the processes of cell renewal in organotypic cultures of the corresponding organs of young and old animals. A correlation between the intensity of regeneration and animal’ age was revealed. The polypeptide complexes reduced the expression of apoptotic factors p53 and caspase 3 and increased the expression of proliferation protein Ki-67. These results provide the basis for further study of the polypeptide complexes as stimulators of regenerative processes in different tissues during ageing.

Correction to: Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer’s Disease

On the page 553 Acknowledgements should be as follows: The study was supported by the Russian Science Foundation (grant 14-25-00024-P).

Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer’s Disease

In primary culture of mouse hippocampal neurons, peptide EDR (200 ng/ml) under conditions of amyloid synaptotoxicity (a model of Alzheimer’s disease) increased the number of mushroom spines by 71% and returned this parameter to the normal level. Under the same conditions, tripeptide KED (200 ng/ml) increased the number of mushroom spines in hippocampal neurons by 20%. Tripeptide EDR can be recommended for further experimental study as a candidate neuroprotective agent for prevention and treatment of Alzheimer’s disease.

Short Peptides Regulate Gene Expression

Short peptides constitute the system of signal molecules regulating the functions of the organism at the molecular, genetic, subcellular, cellular, and tissue levels. One short peptide can regulate dozens of genes, but the molecular mechanism of this process remains unclear. We suppose that short peptides penetrate through the cytoplasmic and nuclear membrane and bind to DNA. Spatial models of DNA—peptide complexes are constructed for 19 short peptides by the docking method. Some peptides have the same binding sites. Peptides KE and EDP bind agat sequence, peptides KEDW and AED to acct sequence, and peptides AEDL and EDL to ctcc sequence.