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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
Cadmium-induced autophagy in rat kidney: An early biomarker of subtoxic exposure
Toxicological Sciences, Volume 121, No. 1, Year 2011
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Description
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. © The Author 2011. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
Authors & Co-Authors
Chargui, Abderrahman
Tunisia, Tunis
Faculté de Médecine de Tunis
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Inserm
France, Nice
Université Côte D'azur
Zekri, Semy
Tunisia, Tunis
Faculté de Médecine de Tunis
France, Paris
Cnrs Centre National de la Recherche Scientifique
Jacquillet, Gregory
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Nice
Université Côte D'azur
Rubera, Isabelle
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Nice
Université Côte D'azur
Ilie, Marius
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Inserm
France, Nice
Université Côte D'azur
France, Nice
Centre Hospitalier Universitaire de Nice, Hôpital Pasteur
Belaïd, Amine
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Inserm
France, Nice
Université Côte D'azur
Duranton, Christophe
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Nice
Université Côte D'azur
Tauc, Michel
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Nice
Université Côte D'azur
Hofman, Paul M.
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Inserm
France, Nice
Université Côte D'azur
France, Nice
Centre Hospitalier Universitaire de Nice, Hôpital Pasteur
Poujeol, Philippe
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Inserm
El-May, Michèle Véronique
Tunisia, Tunis
Faculté de Médecine de Tunis
France, Paris
Cnrs Centre National de la Recherche Scientifique
Mograbi, Baharia
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Inserm
France, Nice
Université Côte D'azur
Statistics
Citations: 131
Authors: 12
Affiliations: 5
Identifiers
Doi:
10.1093/toxsci/kfr031
e-ISSN:
10960929
Research Areas
Cancer
Violence And Injury