Evaluation of low doses BPA-induced perturbation of glycemia by toxicogenomics points to a primary role of pancreatic islets and to the mechanism of toxicity
| Autor: | Immacolata Porreca, Concetta Ambrosino, Fulvio D'Angelo, M De Felice, Danila Cuomo, Massimo Mallardo, Emanuele Carchia, P. J. Almeida, Michele Ceccarelli |
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| Přispěvatelé: | Carchia, E, Porreca, I, Almeida, Pj, D'Angelo, F, Cuomo, D, Ceccarelli, M, De Felice, M, Mallardo, M, Ambrosino, C. |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Blood Glucose
Male Cancer Research medicine.medical_specialty endocrine system Immunology BPA-induced glycemia toxicogenomics pancreatic toxicity Biology Toxicogenetics Islets of Langerhans Mice Cellular and Molecular Neuroscience Phenols In vivo Internal medicine medicine Animals Homeostasis Glucose homeostasis Benzhydryl Compounds geography geography.geographical_feature_category Dose-Response Relationship Drug Pancreatic islets Cell Biology Islet Mice Inbred C57BL Endocrinology medicine.anatomical_structure Toxicity Hepatocytes Original Article Toxicogenomics Ex vivo hormones hormone substitutes and hormone antagonists |
| Zdroj: | Cell death and disease 6 (2015). doi:10.1038/cddis.2015.319 info:cnr-pdr/source/autori:Carchia, E.; Porreca, I.; Almeida, P. J.; D'Angelo, F.; Cuomo, D.; Ceccarelli, M.; De Felice, M.; Mallardo, M.; Ambrosino, C./titolo:Evaluation of low doses BPA-induced perturbation of glycemia by toxicogenomics points to a primary role of pancreatic islets and to the mechanism of toxicity/doi:10.1038%2Fcddis.2015.319/rivista:Cell death and disease/anno:2015/pagina_da:/pagina_a:/intervallo_pagine:/volume:6 Cell Death & Disease |
| DOI: | 10.1038/cddis.2015.319 |
| Popis: | Epidemiologic and experimental studies have associated changes of blood glucose homeostasis to Bisphenol A (BPA) exposure. We took a toxicogenomic approach to investigate the mechanisms of low-dose (1 × 10−9M) BPA toxicity in ex vivo cultures of primary murine pancreatic islets and hepatocytes. Twenty-nine inhibited genes were identified in islets and none in exposed hepatocytes. Although their expression was slightly altered, their impaired cellular level, as a whole, resulted in specific phenotypic changes. Damage of mitochondrial function and metabolism, as predicted by bioinformatics analyses, was observed: BPA exposure led to a time-dependent decrease in mitochondrial membrane potential, to an increase of ROS cellular levels and, finally, to an induction of apoptosis, attributable to the bigger Bax/Bcl-2 ratio owing to activation of NF-κB pathway. Our data suggest a multifactorial mechanism for BPA toxicity in pancreatic islets with emphasis to mitochondria dysfunction and NF-κB activation. Finally, we assessed in vitro the viability of BPA-treated islets in stressing condition, as exposure to high glucose, evidencing a reduced ability of the exposed islets to respond to further damages. The result was confirmed in vivo evaluating the reduction of glycemia in hyperglycemic mice transplanted with control and BPA-treated pancreatic islets. The reported findings identify the pancreatic islet as the main target of BPA toxicity in impairing the glycemia. They suggest that the BPA exposure can weaken the response of the pancreatic islets to damages. The last observation could represent a broader concept whose consideration should lead to the development of experimental plans better reproducing the multiple exposure conditions. |
| Databáze: | OpenAIRE |
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