Research article summary (published 27 Aug 2009):

Stress proteins and oxidative damage in a renal derived cell line exposed to inorganic mercury and lead.

Full Abstract

A close link between stress protein up-regulation and oxidative damage may provide a novel therapeutic tool to counteract nephrotoxicity induced by toxic metals in the human population, mainly in children, of industrialized countries. Here we analysed the time course of the expression of several heat shock proteins, glucose-regulated proteins and metallothioneins in a rat proximal tubular cell line (NRK-52E) exposed to subcytotoxic doses of inorganic mercury and lead. Concomitantly, we used morphological and biochemical methods to evaluate metal-induced cytotoxicity and oxidative damage. In particular, as biochemical indicators of oxidative stress we detected reactive oxygen species (ROS) and nitrogen species (RNS), total glutathione (GSH) and glutathione-S-transferase (GST) activity. Our results clearly demonstrated that mercury increases ROS and RNS levels and the expressions of Hsp25 and inducible Hsp72. These findings are corroborated by evident mitochondrial damage, apoptosis or necrosis. By contrast, lead is unable to up-regulate Hsp72 but enhances Grp78 and activates nuclear Hsp25 translocation. Furthermore, lead causes endoplasmic reticulum (ER) stress, vacuolation and nucleolar segregation. Lastly, both metals stimulate the over-expression of MTs, but with a different time course. In conclusion, in NRK-52E cell line the stress response is an early and metal-induced event that correlates well with the direct oxidative damage induced by mercury. Indeed, different chaperones are involved in the specific nephrotoxic mechanism of these environmental pollutants and work together for cell survival.

Author information

Author/s: Stacchiotti, Alessandra (A); Morandini, Fausta (F); Bettoni, Francesca (F); Schena, Ilaria (I); Lavazza, Antonio (A); Grigolato, Pier Giovanni (PG); Apostoli, Pietro (P); Rezzani, Rita (R); Aleo, Maria Francesca (MF);

Affiliation: Human Anatomy Unit, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Italy.

Grants: 1R01 HL072323-01 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Toxicology (Toxicology), published in Ireland. (Language: eng)

Reference: 2009-Oct; vol 264 (issue 3) : pp 215-24

Dates: Created 2009/09/28; Completed 2009/10/13; Revised 2009/10/15;

PMID: 19720107, status: MEDLINE (last retrieval date: 10/15/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Apoptosis - drug effects Biological Markers - metabolism Cell Line Cell Proliferation - drug effects Cell Survival - drug effects Dose-Response Relationship, Drug Endoplasmic Reticulum - drug effects; metabolism Glutathione - metabolism Glutathione Transferase - metabolism HSP27 Heat-Shock Proteins - metabolism HSP72 Heat-Shock Proteins - metabolism Heat-Shock Proteins - metabolism

Heat-Shock Proteins - metabolism Kidney Tubules, Proximal - drug effects; metabolism; pathology Lead - toxicity Mercuric Chloride - toxicity Metallothionein - metabolism Mitochondria - drug effects; metabolism Molecular Chaperones - metabolism Necrosis Nitric Oxide - metabolism Oxidative Stress - drug effects Rats Reactive Oxygen Species - metabolism Time Factors

Associated Chemicals: Biological Markers (0) ; HSP27 Heat-Shock Proteins (0) ; HSP72 Heat-Shock Proteins (0) ; Heat-Shock Proteins (0) ; Hspa5 protein, rat (0) ; Hspb1 protein, rat (0) ; Molecular Chaperones (0) ; Reactive Oxygen Species (0) ; Nitric Oxide (10102-43-9) ; Glutathione (70-18-8) ; Lead (7439-92-1) ; Mercuric Chloride (7487-94-7) ; lead chloride (7758-95-4) ; Metallothionein (9038-94-2) ; Glutathione Transferase (EC 2.5.1.18)

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