Peptide Regulation of Gene Expression and Protein Synthesis in Bronchial Epithelium

• Published in: Lung 2014-10, Vol.192 (5), p.781-791
• Main Authors: Khavinson, V. Kh, Tendler, S. M., Vanyushin, B. F., Kasyanenko, N. A., Kvetnoy, I. M., Linkova, N. S., Ashapkin, V. V., Polyakova, V. O., Basharina, V. S., Bernadotte, A.
• Format: Article
• Language: English
• Subjects: Analysis; Binding Sites; Bronchi - drug effects; Bronchi - metabolism; Bronchitis; Care and treatment; Cell culture; Cell Differentiation; Cell Line; Cell Proliferation; DNA - chemistry; DNA - metabolism; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelium; Gene expression; Gene Expression Regulation - drug effects; Genetic aspects; Humans; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Nucleic Acid Conformation; Oligopeptides - metabolism; Oligopeptides - pharmacology; Peptides; Physiological aspects; Pneumology/Respiratory System; Protein Biosynthesis - drug effects; Protein synthesis; Respiratory diseases; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; Risk factors; RNA, Messenger - metabolism; Time Factors
• ISSN: 0341-2040; 1432-1750; 1432-1750
• DOI: 10.1007/s00408-014-9620-7

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.