Autophagy: A Major Target of Cadmium Nephrotoxicity
Abderrahman Chargui, Amine Belaïd, Nadir Djerbi, Michèle Véronique El May and Baharia MograbiAffiliation:
Institute of Research on Cancer and Aging of Nice (IRCAN); Université de Nice-Sophia Antipolis; Faculté de Médecine; Avenue de Valombrose; 06108 Nice Cedex 02, France.
AbstractCadmium toxicity remains a major public health concern, despite a huge amount of work to explain its effects. The kidney is the most sensitive organ; and we recently provide the first evidence of a direct upregulation of autophagy by cadmium particularly in response to environmental relevant concentrations. Investigation of autophagy is greatly progressed and various strategies have been reported for studying this molecular process in different biological systems both in physiological and stress conditions. Furthermore, mechanisms of cadmium-induced autophagy in renal cells continue to be of interest given the unknown physiologic function of this metal. Cadmium is persistent within cytosol; it might damage proteins continuously and induces oxidative stress. The aim of this review is a critical analysis of knowledge about autophagic mechanisms induced by cadmium. We also report data obtained in different experimental studies, using cadmium and other xenobiotics, highlighting similarities in the induction of autophagic processes. A more detailed discussion will concern the role of autophagy in cadmium exposed renal proximal convoluted tubule since it is a suitable model system extremely sensitive to environmental stress and cadmium is one of the most nephrotoxic metals to which humans are exposed. We finally conclude that deficiency of autophagic process may be the origin of cadmium nephrotoxicity.
Cadmium, Autophagy, Oxidative stress, ER stress, Ubiquitin.
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