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.
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.
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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