Cadmium-induced autophagy in rat kidney: an early biomarker of subtoxic exposure
| Autor: | Christophe Duranton, Abderrahman Chargui, Amine Belaid, Philippe Poujeol, Michèle V. El May, Marius Ilie, Paul Hofman, Grégory Jacquillet, Isabelle Rubera, Baharia Mograbi, Michel Tauc, Sami Zekri |
|---|---|
| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM), Physiologie cellulaire et moléculaire des systèmes intégrés (PCMSI), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire de PhysioMédecine Moléculaire (LP2M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire CNRS 3093, Université de Nice-Sophia Antipolis, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Université of Tunis |
| Rok vydání: | 2011 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Blotting Western 010501 environmental sciences Biology Toxicology Kidney 01 natural sciences 03 medical and health sciences Downregulation and upregulation medicine Autophagy Animals Rats Wistar ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0105 earth and related environmental sciences Cell Proliferation 0303 health sciences Dose-Response Relationship Drug Cell growth Endoplasmic reticulum Kidney metabolism Immunohistochemistry Rats medicine.anatomical_structure Cell culture Apoptosis Immunology Cancer research Female Biomarkers Cadmium |
| Zdroj: | Toxicological Sciences Toxicological Sciences, Oxford University Press (OUP), 2011, 121 (1), pp.31-42. ⟨10.1093/toxsci/kfr031⟩ |
| ISSN: | 1096-0929 1096-6080 1096-6099 |
| Popis: | Environmental exposures to cadmium (Cd) are a major cause of human toxicity. The kidney is the most sensitive organ; however, the natures of injuries and of adaptive responses have not been adequately investigated, particularly in response to environmental relevant Cd concentrations. In this study, rats received a daily ip injection of low CdCl₂ dose (0.3 mg Cd/kg body mass) and killed at 1, 3, and 5 days of intoxication. Functional, ultrastructural, and biochemical observations were used to evaluate Cd effects. We show that Cd at such subtoxic doses does not affect the tubular functions nor does it induce apoptosis. Meanwhile, Cd accumulates within lysosomes of proximal convoluted tubule (PCT) cells where it triggers cell proliferation and autophagy. By developing an immunohistochemical assay, a punctate staining of light chain 3-II is prominent in Cd-intoxicated kidneys, as compared with control. We provide the evidence of a direct upregulation of autophagy by Cd using a PCT cell line. Compared with the other heavy metals, Cd is the most powerful inducer of endoplasmic reticulum stress and autophagy in PCT cells, in relation to the hypersensitivity of PCT cells. Altogether, these findings suggest that kidney cortex adapts to subtoxic Cd dose by activating autophagy, a housekeeping process that ensures the degradation of damaged proteins. Given that Cd is persistent within cytosol, it might damage proteins continuously and impair at long-term autophagy efficiency. We therefore propose the autophagy pathway as a new sensitive biomarker for renal injury even after exposure to subtoxic Cd doses. |
| Databáze: | OpenAIRE |
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