title: Stress proteins and oxidative damage in a renal derived cell line exposed to inorganic mercury and lead.
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.
authors.affiliation: Human Anatomy Unit, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Stacchiotti
authors.forename: Fausta
authors.initials: F
authors.lastname: Morandini
authors.forename: Francesca
authors.initials: F
authors.lastname: Bettoni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Schena
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavazza
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Grigolato
authors.forename: Pietro
authors.initials: P
authors.lastname: Apostoli
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Aleo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007854:Lead / Q000633:toxicity*; D008627:Mercuric Chloride / Q000633:toxicity*; D008668:Metallothionein / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D000091342:Endoplasmic Reticulum Chaperone BiP; C051684:GRP78 protein, rat; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D018832:Molecular Chaperones; D017382:Reactive Oxygen Species; D007854:Lead; D009569:Nitric Oxide; C029891:lead chloride; D008627:Mercuric Chloride; D008668:Metallothionein; D005982:Glutathione Transferase; D005978:Glutathione