Bisphenol A Modulates Autophagy and Exacerbates Chronic Kidney Damage in Mice
| Autor: | Emilio González Parra, Sebastian Mas, José Luis Morgado-Pascual, Alberto Ruiz Priego, Sandra Rayego-Mateos, Marta Ruiz-Ortega |
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| Přispěvatelé: | [Priego,AR, Parra,EG, Mas,S] Division of Nephrology and Hypertension, IIS-Fundación Jiménez Díaz-UAM/IRSIN, Madrid, Spain. [Morgado-Pascual,JL] Cellular Biology, Physiology and Immunology Department, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Cordoba, Spain. [Ruiz-Ortega,M, Rayego-Mateos,S] Molecular and Cellular Biology in Renal and Vascular Pathology, IIS-Fundación Jiménez Díaz, Universidad Autónoma Madrid Faculty of Medicine, Madrid, Spain., This work was supported by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119, PI20/00140, DTS20/00083, PI16/01298, Red de Investi gación Renal REDINREN: RD16/0009 to M.R-O), Comunidad Autónoma de Madrid FEDER-a way to build Europe (B2017/BMD-3751 NOVELREN-CM to M.R-O), Juan de la Cierva incorporacion grant: IJC2018-035187-I to S.R-M, Juan de la Cierva de Formacion grant: FJC2019-042028-I to J.M-P and Fundacion Conchita Rabago grant to A.R.P, 'Convocatoria Dinamización Europa Investigación 2019' MINECO (EIN2019-103294 to M.R-O and SR-M), Innovation programme under the Marie Skłodowska-Curie grant of the European Union’s Horizon 2020 (IMProve-PD ID: 812699) to M.R-O and Sociedad Española de Nefrologia to S.R-M |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice Inbred Strains::Mice Inbred C57BL [Medical Subject Headings] Autophagosome maturation 030232 urology & nephrology Riñón Apoptosis Anatomy::Urogenital System::Urinary Tract::Kidney::Nephrons::Kidney Tubules [Medical Subject Headings] Kidney medicine.disease_cause Diseases::Female Urogenital Diseases and Pregnancy Complications::Female Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Renal Insufficiency Chronic [Medical Subject Headings] Antioxidants Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antioxidants [Medical Subject Headings] Mice 0302 clinical medicine Bisphenol A Organisms::Eukaryota::Animals [Medical Subject Headings] oxidative stress Biology (General) Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings] Spectroscopy Chemistry Diseases::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases [Medical Subject Headings] Estrés oxidativo General Medicine Computer Science Applications Kidney Tubules medicine.anatomical_structure Female Kidney Diseases MAP1LC3B hormones hormone substitutes and hormone antagonists medicine.medical_specialty endocrine system autophagy QH301-705.5 ATG5 Autofagia Article Catalysis Cell Line Proinflammatory cytokine Inorganic Chemistry 03 medical and health sciences Phenols Bisfenol A glicidil metacrilato Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons Cyclic::Hydrocarbons Aromatic::Benzene Derivatives::Phenols [Medical Subject Headings] Internal medicine medicine Animals Humans Benzhydryl Compounds Renal Insufficiency Chronic Physical and Theoretical Chemistry Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Autophagy [Medical Subject Headings] Molecular Biology QD1-999 Inflamación urogenital system Organic Chemistry Autophagy fibrosis Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons Cyclic::Hydrocarbons Aromatic::Benzene Derivatives::Benzhydryl Compounds [Medical Subject Headings] medicine.disease Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings] Mice Inbred C57BL Oxidative Stress 030104 developmental biology Endocrinology inflammation Oxidative stress Kidney disease |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 13 International Journal of Molecular Sciences, Vol 22, Iss 7189, p 7189 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22137189 |
| Popis: | BACKGROUND: Bisphenol A (BPA) is a ubiquitous environmental toxin that accumulates in chronic kidney disease (CKD). Our aim was to explore the effect of chronic exposition of BPA in healthy and injured kidney investigating potential mechanisms involved. METHODS: In C57Bl/6 mice, administration of BPA (120 mg/kg/day, i.p for 5 days/week) was done for 2 and 5 weeks. To study BPA effect on CKD, a model of subtotal nephrectomy (SNX) combined with BPA administration for 5 weeks was employed. In vitro studies were done in human proximal tubular epithelial cells (HK-2 line). RESULTS: Chronic BPA administration to healthy mice induces inflammatory infiltration in the kidney, tubular injury and renal fibrosis (assessed by increased collagen deposition). Moreover, in SNX mice BPA exposure exacerbates renal lesions, including overexpression of the tubular damage biomarker Hepatitis A virus cellular receptor 1 (Havcr-1/KIM-1). BPA upregulated several proinflammatory genes and increased the antioxidant response [Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme Oxygenase-1 (Ho-1) and NAD(P)H dehydrogenase quinone 1 (Nqo-1)] both in healthy and SNX mice. The autophagy process was modulated by BPA, through elevated autophagy-related gene 5 (Atg5), autophagy-related gene 7 (Atg7), Microtubule-associated proteins 1A/1B light chain 3B (Map1lc3b/Lc3b) and Beclin-1 gene levels and blockaded the autophagosome maturation and flux (p62 levels). This autophagy deregulation was confirmed in vitro. CONCLUSIONS: BPA deregulates autophagy flux and redox protective mechanisms, suggesting a potential mechanism of BPA deleterious effects in the kidney. |
| Databáze: | OpenAIRE |
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