Peptide Regulation of Gene Expression and Protein Synthesis in Bronchial Epithelium

Khavinson, V. Kh.; Tendler, Solomon; Vanyushin, B. F.; Kasyanenko, N. A.; Kvetnoy, I. M.; Linkova, N. S.; Ashapkin, Vasily V.; Polyakova, V. O.; Башарина, В С; Bernadotte, Alexandra

doi:10.1007/s00408-014-9620-7

Cited by 23 publications

(18 citation statements)

References 34 publications

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“…Despite its importance, FOXA2 has not been targeted for the development of novel mucoregulators, perhaps due to the complexity in gene regulation, posttranslational modifications, and toxicity associated with its regulation of multiple cellular processes. Recently, the peptide ADEL (Ala-Asp-Glu-Leu) was found to relieve bacterialmediated inflammation and improve lung function while boosting FOXA2 expression (88). Additionally, GLP-1 analogs were shown to reduce mortality and improve lung function in mice with acute obstructive lung disease (89).…”

Section: Discussionmentioning

confidence: 99%

Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis

2020

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Forkhead box (FOX) proteins are transcriptional factors that regulate various cellular processes. This minireview provides an overview of FOXA2 functions, with a special emphasis on the regulation airway mucus homeostasis in both healthy and diseased lungs. FOXA2 plays crucial roles during lung morphogenesis, surfactant protein production, goblet cell differentiation and mucin expression. In healthy airways, FOXA2 exerts a tight control over goblet cell development and mucin biosynthesis. However, in diseased airways, microbial infections and proinflammatory responses deplete FOXA2 expression, resulting in uncontrolled goblet cell hyperplasia and metaplasia, mucus hypersecretion, and impaired mucociliary clearance of pathogens. Furthermore, accumulated mucus clogs the airways and creates a niche environment for persistent microbial colonization and infection, leading to acute exacerbation and deterioration of pulmonary function in patients with chronic lung diseases. Various studies have shown that FOXA2 inhibition is mediated through induction of antagonistic EGFR and IL-13R-STAT6 signaling pathways as well as through posttranslational modifications induced by microbial infections. An improved understanding of how bacterial pathogens inactivate FOXA2 may pave the way for developing therapeutics that preserve the protein's function, which in turn, will improve the mucus status and mucociliary clearance of pathogens, reduce microbial-mediated acute exacerbation and restore lung function in patients with chronic lung diseases.

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Section: Discussionmentioning

confidence: 99%

Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis

2020

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“…ADEL also activateed 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) [44].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of EDR Peptide in Mouse Model of Huntington's Disease

Хавинсон¹,

Линькова²,

Kukanova³

et al. 2017

J Neurol Neurosci

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Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder. The study in functioning and aging of neurons may give an opportunity to regulate these processes. Previous investigations demonstrated the ability of EDR peptide (Glu-Asp-Arg) to penetrate a cell nucleus and stimulate gene expression. The data obtained prompt EDR peptide capability to restore the morphology of spines in striatum neurons in Huntington's disease (HD) mouse model. EDR peptide has been shown by us to bind the DNA in solution (absorption spectroscopy and dynamic light scattering) and in a computer model. The proposed model suggests that EDR peptide binds specific binding site oligo (dCG) along the DNA minor groove.

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“…In order to mimic conditions of the nucleus, some concentration variations allowed us to consider electrostatic interactions between the peptide and DNA. This saline condition has been previously tested and successfully used for the study of biologically active molecules interaction in solution [23].…”

Section: Uv-spectroscopy and Circular Dichroismmentioning

confidence: 99%

Tetrapeptide KEDW Interacts with DNA and Regulates Gene Expression

Khavinson¹,

Tendler²,

Kasyanenko³

et al. 2015

Am. J. Biomed. Sci.

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Peptide KEDW (Lys-Glu-Asp-Trp-NH2) is known to reduce the blood glucose level in rats with streptozotocin-and alloxan-induced diabetes mellitus. Here, we examine the influence of KEDW peptide on cell differentiation and DNA structure. KEDW peptide increased the expression of PDX1, NGN3, PAX6, FOXA2, NKX2-2, NKX6.1, and PAX4 genes but decreased MNX1 and HOXA3 gene expression when added to pancreatic cell culture. Moreover, KEDW peptide caused an increase in expression of PDX1, NGN3, PAX6, FOXA2, NKX2-2, NKX6.1, and PAX4 proteins without affecting synthesis of MNX1 and HOXA3 when added to pancreatic cell culture. Results obtained through physical methods (UV-visible absorption, circular dichroism) and molecular modelling methods suggest that the peptide binds to DNA along the major groove. Experimental and theoretical data provided a 3D model of the stable DNA-peptide complex. We propose that regulation of differentiation factor expression in pancreatic (endocrine) cells by KEDW peptide occurs through specific binding of the peptide to regulatory elements of corresponding genes.

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Peptide Regulation of Gene Expression and Protein Synthesis in Bronchial Epithelium

Cited by 23 publications

References 34 publications

Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis

Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis

Neuroprotective Effect of EDR Peptide in Mouse Model of Huntington's Disease

Tetrapeptide KEDW Interacts with DNA and Regulates Gene Expression

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