Advanced glycation end-products affect transcription factors regulating insulin gene expression
| Autor: | Daniela Storace, Alessandra Puddu, Patrizio Odetti, Giorgio Luciano Viviani |
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| Rok vydání: | 2010 |
| Předmět: |
Glycation End Products
Advanced endocrine system medicine.medical_specialty medicine.medical_treatment Biophysics FOXO1 Biology digestive system Biochemistry Cell Line Transcription (biology) Glycation Internal medicine Insulin-Secreting Cells medicine Humans Insulin Phosphorylation Molecular Biology Transcription factor Regulation of gene expression Cell Nucleus Homeodomain Proteins Forkhead Box Protein O3 nutritional and metabolic diseases Forkhead Transcription Factors Cell Biology medicine.anatomical_structure Endocrinology Gene Expression Regulation Trans-Activators Beta cell Pancreas hormones hormone substitutes and hormone antagonists |
| Zdroj: | Biochemical and biophysical research communications. 395(1) |
| ISSN: | 1090-2104 |
| Popis: | Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic beta-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression. |
| Databáze: | OpenAIRE |
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