In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis
| Autor: | Giancarlo Troncone, Danilo Fiore, Cristina Quintavalle, F. De Micco, Monica Brenca, A. Bianco, Gerolama Condorelli, F Apone, M F Romano, Simona Romano, M A Zabatta, Carlo Briguori |
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| Přispěvatelé: | Quintavalle, Cristina, Brenca, Monica, De Micco, F, Fiore, Danilo, Romano, Simona, Romano, MARIA FIAMMETTA, Apone, F, Bianco, A, Zabatta, Assunta, Troncone, Giancarlo, Briguori, C, Condorelli, Gerolama |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Cancer Research kidney p38 mitogen-activated protein kinases Immunology Caspase 3 Biology contrast media Cellular and Molecular Neuroscience renal cells prevention medicine Humans Cells Cultured Aged Enzyme Assays chemistry.chemical_classification Aged 80 and over Kidney Reactive oxygen species Kinase Acute kidney injury JNK Mitogen-Activated Protein Kinases apoptosis Cell Biology Acute Kidney Injury Middle Aged medicine.disease apoptosi Cell biology medicine.anatomical_structure Kidney Tubules bcl-2 Homologous Antagonist-Killer Protein chemistry Apoptosis Cancer research Female Original Article Reactive Oxygen Species Bcl-2 Homologous Antagonist-Killer Protein Signal Transduction |
| Zdroj: | Cell Death & Disease |
| Popis: | Contrast-induced nephropathy accounts for 410% of all causes of hospital-acquired renal failure, causes a prolonged in- hospital stay and represents a powerful predictor of poor early and late outcome. Mechanisms of contrast-induced nephropathy are not completely understood. In vitro data suggests that contrast media (CM) induces a direct toxic effect on renal tubular cells through the activation of the intrinsic apoptotic pathway. It is unclear whether this effect has a role in the clinical setting. In this work, we evaluated the effects of CM both in vivo and in vitro. By analyzing urine samples obtained from patients who experienced contrast-induced acute kidney injury (CI-AKI), we verified, by western blot and immunohistochemistry, that CM induces tubular renal cells apoptosis. Furthermore, in cultured cells, CM caused a dose–response increase in reactive oxygen species (ROS) production, which triggered Jun N-terminal kinases (JNK1/2) and p38 stress kinases marked activation and thus apoptosis. Inhibition of JNK1/2 and p38 by different approaches (i.e. pharmacological antagonists and transfection of kinase- death mutants of the upstream p38 and JNK kinases) prevented CM-induced apoptosis. Interestingly, N-acetylcysteine inhibited ROS production, and thus stress kinases and apoptosis activation. Therefore, we conclude that CM-induced tubular renal cells apoptosis represents a key mechanism of CI-AKI. |
| Databáze: | OpenAIRE |
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